WorldWideScience

Sample records for delineating genetic alterations

  1. Solid-State (13)C NMR Delineates the Architectural Design of Biopolymers in Native and Genetically Altered Tomato Fruit Cuticles.

    Science.gov (United States)

    Chatterjee, Subhasish; Matas, Antonio J; Isaacson, Tal; Kehlet, Cindie; Rose, Jocelyn K C; Stark, Ruth E

    2016-01-11

    Plant cuticles on outer fruit and leaf surfaces are natural macromolecular composites of waxes and polyesters that ensure mechanical integrity and mitigate environmental challenges. They also provide renewable raw materials for cosmetics, packaging, and coatings. To delineate the structural framework and flexibility underlying the versatile functions of cutin biopolymers associated with polysaccharide-rich cell-wall matrices, solid-state NMR spectra and spin relaxation times were measured in a tomato fruit model system, including different developmental stages and surface phenotypes. The hydrophilic-hydrophobic balance of the cutin ensures compatibility with the underlying polysaccharide cell walls; the hydroxy fatty acid structures of outer epidermal cutin also support deposition of hydrophobic waxes and aromatic moieties while promoting the formation of cell-wall cross-links that rigidify and strengthen the cuticle composite during fruit development. Fruit cutin-deficient tomato mutants with compromised microbial resistance exhibit less efficient local and collective biopolymer motions, stiffening their cuticular surfaces and increasing their susceptibility to fracture.

  2. Delineating genetic relationships among the Maya.

    Science.gov (United States)

    Ibarra-Rivera, Lisa; Mirabal, Sheyla; Regueiro, Manuela M; Herrera, Rene J

    2008-03-01

    By 250 AD, the Classic Maya had become the most advanced civilization within the New World, possessing the only well-developed hieroglyphic writing system of the time and an advanced knowledge of mathematics, astronomy and architecture. Though only ruins of the empire remain, 7.5 million Mayan descendants still occupy areas of Mexico, Guatemala, Belize, El Salvador, and Honduras. Although they inhabit distant and distinct territories, speak more than 28 languages, and have been historically divided by warfare and a city-state-like political system, and they share characteristics such as rituals, artistic, architectural motifs that distinguish them as unequivocally Maya. This study was undertaken to determine whether these similarities among Mayan communities mirror genetic affinities or are merely a reflection of their common culture. Four Mayan populations were investigated (i.e., the K'iche and Kakchikel from Guatemala and the Campeche and Yucatan from Mexico) and compared with previously published populations across 15 autosomal STR loci. As a whole, the Maya emerge as a distinct group within Mesoamerica, indicating that they are more similar to each other than to other Mesoamerican groups. The data suggest that although geographic and political boundaries existed among Mayan communities, genetic exchanges between the different Mayan groups have occurred, supporting theories of extensive trading throughout the empire. 2007 Wiley-Liss, Inc.

  3. Genetic Alterations in Glioma

    International Nuclear Information System (INIS)

    Bralten, Linda B. C.; French, Pim J.

    2011-01-01

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  4. Delineating the genetic heterogeneity of OCA in Hungarian patients

    OpenAIRE

    F?bos, Be?ta; Farkas, Katalin; T?th, Lola; Sul?k, Adrienn; Tripolszki, Korn?lia; Tihanyi, Mariann; N?meth, R?ka; Vas, Krisztina; Csoma, Zsanett; Kem?ny, Lajos; Sz?ll, M?rta; Nagy, Nikoletta

    2017-01-01

    Background Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1?7). Methods The most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients ...

  5. Colorectal Cancer Genetic Heterogeneity Delineated by Multi-Region Sequencing.

    Directory of Open Access Journals (Sweden)

    You-Wang Lu

    Full Text Available Intratumor heterogeneity (ITH leads to an underestimation of the mutational landscape portrayed by a single needle biopsy and consequently affects treatment precision. The extent of colorectal cancer (CRC genetic ITH is not well understood in Chinese patients. Thus, we conducted deep sequencing by using the OncoGxOne™ Plus panel, targeting 333 cancer-specific genes in multi-region biopsies of primary and liver metastatic tumors from three Chinese CRC patients. We determined that the extent of ITH varied among the three cases. On average, 65% of all the mutations detected were common within individual tumors. KMT2C aberrations and the NCOR1 mutation were the only ubiquitous events. Subsequent phylogenetic analysis showed that the tumors evolved in a branched manner. Comparison of the primary and metastatic tumors revealed that PPP2R1A (E370X, SETD2 (I1608V, SMAD4 (G382T, and AR splicing site mutations may be specific to liver metastatic cancer. These mutations might contribute to the initiation and progression of distant metastasis. Collectively, our analysis identified a substantial level of genetic ITH in CRC, which should be considered for personalized therapeutic strategies.

  6. Delineating the genetic heterogeneity of OCA in Hungarian patients.

    Science.gov (United States)

    Fábos, Beáta; Farkas, Katalin; Tóth, Lola; Sulák, Adrienn; Tripolszki, Kornélia; Tihanyi, Mariann; Németh, Réka; Vas, Krisztina; Csoma, Zsanett; Kemény, Lajos; Széll, Márta; Nagy, Nikoletta

    2017-06-19

    Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1-7). The most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients (n = 13). Mutation screening and polymorphism analysis were performed by direct sequencing on TYR, OCA2, SLC45A2 genes. Although the clinical features of the investigated Hungarian OCA patients were identical, the molecular genetic data suggested OCA1 subtype in eight cases and OCA4 subtype in two cases. The molecular diagnosis was not clearly identifiable in three cases. In four patients, two different heterozygous known pathogenic or predicted to be pathogenic mutations were present. Seven patients had only one pathogenic mutation, which was associated with non-pathogenic variants in six cases. In two patients no pathogenic mutation was identified. Our results suggest that the concomitant screening of the non-pathogenic variants-which alone do not cause the development of OCA, but might have clinical significance in association with a pathogenic variant-is important. Our results also show significant variation in the disease spectrum compared to other populations. These data also confirm that the concomitant analysis of OCA genes is critical, providing new insights to the phenotypic diversity of OCA and expanding the mutation spectrum of OCA genes in Hungarian patients.

  7. Rare endocrine cancers have novel genetic alterations

    Science.gov (United States)

    A molecular characterization of adrenocortical carcinoma, a rare cancer of the adrenal cortex, analyzed 91 cases for alterations in the tumor genomes and identified several novel genetic mutations as likely mechanisms driving the disease as well as whole genome doubling as a probable driver of the disease.

  8. Genetic alterations in hepatocellular carcinoma: An update

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  9. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  10. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  11. Parental Virtue and Prenatal Genetic Alteration Research.

    Science.gov (United States)

    Tonkens, Ryan

    2015-12-01

    Although the philosophical literature on the ethics of human prenatal genetic alteration (PGA) purports to inform us about how to act, it rarely explicitly recognizes the perspective of those who will be making the PGA decision in practice. Here I approach the ethics of PGA from a distinctly virtue-based perspective, taking seriously what it means to be a good parent making this decision for one's child. From this perspective, I generate a sound verdict on the moral standing of human PGA (research): given the current state of the art, good parents have compelling reason not to consent to PGA (research) for their child, especially as part of the first wave(s) of PGA research participants and especially for non-medically oriented purposes. This is because doing otherwise is inconsistent with a plausible and defensible understanding of virtuous parenting and parental virtues, founded on a genuine concern for promoting the overall flourishing of the eventual child. In essence, given the current and foreseeable state of the art, parents who allow prenatal genetic alteration of their children are less-than-virtuous parents to those children, even in cases where they have a right to do so and even if PGA turns out to be beneficial to the eventual child.

  12. Application of plurigaussian simulation to delineate the layout of alteration domains in Sungun copper deposit

    Science.gov (United States)

    Talebi, Hassan; Asghari, Omid; Emery, Xavier

    2013-12-01

    An accurate estimation of mineral grades in ore deposits with heterogeneous spatial variations requires defining geological domains that differentiate the types of mineralogy, alteration and lithology. Deterministic models define the layout of the domains based on the interpretation of the drill holes and do not take into account the uncertainty in areas with fewer data. Plurigaussian simulation (PGS) can be an alternative to generate multiple numerical models of the ore body, with the aim of assessing the uncertainty in the domain boundaries and improving the geological controls in the characterization of quantitative attributes. This study addresses the application of PGS to Sungun porphyry copper deposit (Iran), in order to simulate the layout of four hypogene alteration zones: potassic, phyllic, propylitic and argillic. The aim of this study is to construct numerical models in which the alteration structures reflect the evolution observed in the geology.

  13. Genetic alterations and epigenetic changes in hepatocarcinogenesis

    Directory of Open Access Journals (Sweden)

    Luz Stella Hoyos Giraldo

    2007-02-01

    Full Text Available

    Hepatocarcinogenesis as hepatocellular carcinoma (HCC is associated with background of chronic liver disease usually in association with cirrhosis, marked hepatic fibrosis, hepatitis B virus (HBV and/or hepatitis virus (HCV infection, chronic inflammation, Aflatoxin B1(AFB1 exposure, chronic alcoholism, metabolic disorder of the liver and necroinflamatory liver disease. Hepatocarcinogenesis involve two mechanisms, genetic alterations (with changes in the cell's DNA sequence and epigenetic changes (without changes in the cell's DNA sequence, but changes in the pattern of gene expression that can persist through one or more generations (somatic sense. Hepatocarcinogenesis is associated with activation of oncogenes and decreased expression of tumor suppressor genes (TSG; include those involved in cell cycle control, apoptosis, DNA repair, immortalization and angiogenesis. AFB1 is metabolized in the liver into a potent carcinogen, aflatoxin 8, 9-epoxide, which is detoxified by epoxide hydrolase (EPHX and glutathione S-transferase M1 (GSTM1.

    A failure of detoxification processes can allow to mutagenic metabolite to bind to DNA and inducing P53 mutation. Genetic polymorphism of EPHX and GSTM1 can make individuals more susceptible to AFB1. Epigenetic inactivation of GSTP1 by promoter hypermethylation plays a role in the development of HCC because, it leads that electrophilic metabolite increase DNA damage and mutations. HBV DNA integration into the host chromosomal DNA of hepatocytes has been detected in HBV-related HCC.

    DNA tumor viruses cause cancer mainly by interfering with cell cycle controls, and activating the cell's replication machinery by blocking the action of key TSG. HBx protein is a

  14. Genetic Alterations in Pesticide Exposed Bolivian Farmers

    DEFF Research Database (Denmark)

    Jørs, Erik; González, Ana Rosa; Ascarrunz, Maria Eugenia

    2007-01-01

    : Questionnaires were applied and blood tests taken from 81 volunteers from La Paz County, of whom 48 were pesticide exposed farmers and 33 non-exposed controls. Sixty males and 21 females participated with a mean age of 37.3 years (range 17-76). Data of exposure and possible genetic damage were collected...... and evaluated by well known statistical methods, controlling for relevant confounders. To measure genetic damage chromosomal aberrations and the comet assay analysis were performed. Results: Pesticide exposed farmers had a higher degree of genetic damage compared to the control group. The number of chromosomal......, probably related to exposure to pesticides. Due to the potentially negative long term health effects of genetic damage on reproduction and the development of cancer, preventive measures are recommended. Effective control with imports and sales, banning of the most toxic pesticides, education...

  15. Genetic delineation between and within the widespread coccolithophore morpho-species Emiliania huxleyi and Gephyrocapsa oceanica (Haptophyta).

    Science.gov (United States)

    Bendif, El Mahdi; Probert, Ian; Carmichael, Margaux; Romac, Sarah; Hagino, Kyoko; de Vargas, Colomban

    2014-02-01

    Emiliania huxleyi and Gephyrocapsa oceanica are abundant coccolithophore morpho-species that play key roles in ocean carbon cycling due to their importance as both primary producers and cal-cifiers. Global change processes such as ocean acidification impact these key calcifying species. The physiology of E. huxleyi, a developing model species, has been widely studied, but its genetic delineation from G. oceanica remains unclear due to a lack of resolution in classical genetic markers. Using nuclear (18S rDNA and 28S rDNA), mitochondrial (cox1, cox2, cox3, rpl16, and dam), and plastidial (16S rDNA, rbcL, tufA, and petA) DNA markers from 99 E. huxleyi and 44 G. oceanica strains, we conducted a multigene/multistrain survey to compare the suitability of different markers for resolving phylogenetic patterns within and between these two morpho-species. The nuclear genes tested did not provide sufficient resolution to discriminate between the two morpho-species that diverged only 291Kya. Typical patterns of incomplete lineage sorting were generated in phylogenetic analyses using plastidial genes. In contrast, full morpho-species delineation was achieved with mitochondrial markers and common intra-morpho-species phylogenetic patterns were observed despite differing rates of DNA substitution. Mitochondrial genes are thus promising barcodes for distinguishing these coccolithophore morpho-species, in particular in the context of environmental monitoring. © 2013 Phycological Society of America.

  16. Genetic alterations in syndromes with oral manifestations

    Directory of Open Access Journals (Sweden)

    Krishnamurthy Anuthama

    2013-01-01

    Full Text Available Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome.

  17. Conservation genetics of the capercaillie in Poland - Delineation of conservation units.

    Science.gov (United States)

    Rutkowski, Robert; Zawadzka, Dorota; Suchecka, Ewa; Merta, Dorota

    2017-01-01

    The capercaillie (Tetrao urogallus) is one of Poland's most endangered bird species, with an estimated population of 380-500 individuals in four isolated areas. To study these natural populations in Poland further, more than 900 non-invasive genetic samples were collected, along with samples from 59 birds representing large, continuous populations in Sweden and Russia; and from two centres in Poland breeding capercaillie. Microsatellite polymorphism at nine loci was then analysed to estimate within-population genetic diversity and genetic differentiation among populations. The results confirmed that isolation of populations and recent decreases in their sizes have reduced genetic diversity among capercaillie in Poland, with all the country's natural populations found to be experiencing the genetic after-effects of demographic bottlenecks. The results of analyses of genetic differentiation and structure further suggest the presence of a 'lowland' cluster (encompassing birds of the Augustowska and Solska Primaeval Forests in Poland, and of Sweden and Russia), and a Carpathian cluster. Capercaillie from Sweden and Russia are also found to differ markedly. The Polish lowland populations seem more closely related to birds from Scandinavia. Our genetic analysis also indicates that the stocks at breeding centres are of a high genetic diversity effectively reflecting the origins of founder individuals, though identification of ancestry requires further study in the case of some birds. Overall, the results sustain the conclusion that the Polish populations of capercaillie from the Carpathians and the lowlands should be treated as independent Management Units (MUs). This is to say that the breeding lines associated with these two sources should be maintained separately at breeding centres. The high level of genetic differentiation of birds from the Solska Primaeval Forest suggests that this population should also be assigned the status of independent MU.

  18. Conservation genetics of the capercaillie in Poland - Delineation of conservation units.

    Directory of Open Access Journals (Sweden)

    Robert Rutkowski

    Full Text Available The capercaillie (Tetrao urogallus is one of Poland's most endangered bird species, with an estimated population of 380-500 individuals in four isolated areas. To study these natural populations in Poland further, more than 900 non-invasive genetic samples were collected, along with samples from 59 birds representing large, continuous populations in Sweden and Russia; and from two centres in Poland breeding capercaillie. Microsatellite polymorphism at nine loci was then analysed to estimate within-population genetic diversity and genetic differentiation among populations. The results confirmed that isolation of populations and recent decreases in their sizes have reduced genetic diversity among capercaillie in Poland, with all the country's natural populations found to be experiencing the genetic after-effects of demographic bottlenecks. The results of analyses of genetic differentiation and structure further suggest the presence of a 'lowland' cluster (encompassing birds of the Augustowska and Solska Primaeval Forests in Poland, and of Sweden and Russia, and a Carpathian cluster. Capercaillie from Sweden and Russia are also found to differ markedly. The Polish lowland populations seem more closely related to birds from Scandinavia. Our genetic analysis also indicates that the stocks at breeding centres are of a high genetic diversity effectively reflecting the origins of founder individuals, though identification of ancestry requires further study in the case of some birds. Overall, the results sustain the conclusion that the Polish populations of capercaillie from the Carpathians and the lowlands should be treated as independent Management Units (MUs. This is to say that the breeding lines associated with these two sources should be maintained separately at breeding centres. The high level of genetic differentiation of birds from the Solska Primaeval Forest suggests that this population should also be assigned the status of independent MU.

  19. Distinct genetic alterations in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Hassan Ashktorab

    Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.

  20. Genetic Alterations in Intervertebral Disc Disease

    Directory of Open Access Journals (Sweden)

    Nikolay L. Martirosyan

    2016-11-01

    Full Text Available Background: Intervertebral disc degeneration (IVDD is considered a multifactorial disease. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single nucleotide polymorphisms (SNPs that are associated with IVDD.Aim: This review explores and presents updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD.Results: SNPs in the genes coding for structural proteins linked with IVDD or disc bulging include the Sp1 polymorphism of COL1A1, Trp3 polymorphism of COL9A3, several polymorphisms of COL11A1 and COL11A2, and a variable number tandem repeat polymorphism of ACAN. The rs4148941 SNP of CHST3 coding for an aggrecan sulfation enzyme is also associated with IVDD. The FokI, TaqI, and ApaI SNPs of the vitamin D receptor gene that is involved in chondrocyte functioning are also associated with IVDD. SNPs relevant to cytokine imbalance in IVDD include 889C/T of IL1a and 15T/A, as well as other SNPs (rs1800795, rs1800796, and rs1800797, of IL6, with effects limited to certain genders and populations. SNPs in collagenase genes include -1605G/D (guanine insertion/deletion of MMP1, -1306C/T of MMP2, -1562C/T and a 5-adenosine (5A variant (in the promotor region of MMP3, -1562C/T of MMP9, and -378T/C of MMP-14. SNPs in aggrecanase genes include 1877T/U of ADAMTS-4 and rs162509 of ADAMTS-5. Among the apoptosis-mediating genes, 1595T/C of the caspase 9 gene, 1525A/G and 1595T/C of the TRAIL gene, and 626C/G of the death receptor 4 gene (DR4 are SNPs associated with IVDD. Among the growth factors involved in disc homeostasis, the rs4871857 SNP of GDF5 was associated with IVDD. VEGF SNPs -2578C/A and -634G/C could foster neovascularization observed in IVDD.Conclusion: Improved understanding of the numerous genetic variants behind various

  1. Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population

    Directory of Open Access Journals (Sweden)

    Jaworek Thomas J

    2012-06-01

    Full Text Available Abstract Background Oculocutaneous albinism (OCA is caused by a group of genetically heterogeneous inherited defects that result in the loss of pigmentation in the eyes, skin and hair. Mutations in the TYR, OCA2, TYRP1 and SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has been conducted to study the spectrum of OCA alleles prevailing in Pakistani albino populations. Methods We enrolled 40 large Pakistani families and screened them for OCA genes and a candidate gene, SLC24A5. Protein function effects were evaluated using in silico prediction algorithms and ex vivo studies in human melanocytes. The effects of splice-site mutations were determined using an exon-trapping assay. Results Screening of the TYR gene revealed four known (p.Arg299His, p.Pro406Leu, p.Gly419Arg, p.Arg278* and three novel mutations (p.Pro21Leu, p.Cys35Arg, p.Tyr411His in ten families. Ex vivo studies revealed the retention of an EGFP-tagged mutant (p.Pro21Leu, p.Cys35Arg or p.Tyr411His tyrosinase in the endoplasmic reticulum (ER at 37°C, but a significant fraction of p.Cys35Arg and p.Tyr411His left the ER in cells grown at a permissive temperature (31°C. Three novel (p.Asp486Tyr, p.Leu527Arg, c.1045-15 T > G and two known mutations (p.Pro743Leu, p.Ala787Thr of OCA2 were found in fourteen families. Exon-trapping assays with a construct containing a novel c.1045-15 T > G mutation revealed an error in splicing. No mutation in TYRP1, SLC45A2, and SLC24A5 was found in the remaining 16 families. Clinical evaluation of the families segregating either TYR or OCA2 mutations showed nystagmus, photophobia, and loss of pigmentation in the skin or hair follicles. Most of the affected individuals had grayish-blue colored eyes. Conclusions Our results show that ten and fourteen families harbored mutations in the TYR and OCA2 genes, respectively. Our findings, along with the results of previous studies, indicate that the p.Cys35Arg, p.Arg278

  2. The genetic alteration of p53 in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Il; Baik, Hee Jong; Kim, Chang Min; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-01-01

    Genetic alterations in the p53 gene have been detected in various human malignancies, and its alterations inactive the function of p53 as a tumor suppressor. Point mutation and gene deletion are the main mechanisms of p53 inactivation. To determine the incidence of genetic alteration of p53 and their clinical implications in Korean patients of esophageal cancer, we investigated p53 alterations in 26 esophageal cancer tissues paired with its normal tissue by Southern blot analysis, PCR-SSCP, and direct sequencing. Allelic loss of chromosome 17p occurred in 12 out of 21 informative cases(57%) by Southern blot analysis, and 16 cases showed mobility shift in PCR-SSCP, so overall incidence of p53 gene alterations was 77%(20/26). The mutations detected was randomly dispersed over exon4-8 and was frequently G-T transversion and C:T transitions. Three identical mutations were clustered at codon 213 suggested the same etiologic agents in this cases. The p53 gene alterations play a significant role in the development of esophageal cancers, however, no relationship between p53 mutation and clinical data was detected so far. 9 refs. (Author).

  3. Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo)

    Science.gov (United States)

    Bertola, L. D.; Jongbloed, H.; van der Gaag, K. J.; de Knijff, P.; Yamaguchi, N.; Hooghiemstra, H.; Bauer, H.; Henschel, P.; White, P. A.; Driscoll, C. A.; Tende, T.; Ottosson, U.; Saidu, Y.; Vrieling, K.; de Iongh, H. H.

    2016-08-01

    Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.

  4. Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo).

    Science.gov (United States)

    Bertola, L D; Jongbloed, H; van der Gaag, K J; de Knijff, P; Yamaguchi, N; Hooghiemstra, H; Bauer, H; Henschel, P; White, P A; Driscoll, C A; Tende, T; Ottosson, U; Saidu, Y; Vrieling, K; de Iongh, H H

    2016-08-04

    Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while the only remaining population in Asia is considered to be distinct (Panthera leo persica). This distinction is disputed both by morphological and genetic data. In this study we introduce the lion as a model for African phylogeography. Analyses of mtDNA sequences reveal six supported clades and a strongly supported ancestral dichotomy with northern populations (West Africa, Central Africa, North Africa/Asia) on one branch, and southern populations (North East Africa, East/Southern Africa and South West Africa) on the other. We review taxonomies and phylogenies of other large savannah mammals, illustrating that similar clades are found in other species. The described phylogeographic pattern is considered in relation to large scale environmental changes in Africa over the past 300,000 years, attributable to climate. Refugial areas, predicted by climate envelope models, further confirm the observed pattern. We support the revision of current lion taxonomy, as recognition of a northern and a southern subspecies is more parsimonious with the evolutionary history of the lion.

  5. Genetic alterations in head and neck squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Nagai M.A.

    1999-01-01

    Full Text Available The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations and tumor suppressor gene inactivation (loss of function mutations, leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease.

  6. The genetic alteration of retinoblastoma gene in esophageal cancer

    International Nuclear Information System (INIS)

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it's alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author)

  7. The genetic alteration of retinoblastoma gene in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Il; Shim, Yung Mok; Kim, Chang Min [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-12-01

    Retinoblastoma(RB) gene is the prototype of tumor suppressor gene and it`s alteration have been frequently observed in a large number of human tumors. To investigate the role of RB in esophageal cancer, we studied 36 esophageal cancer tissues with Southern blot analysis to detect gross LOH and PCR-SSCP method to find minute LOH and mutation, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. Allelic loss of chromosome 13q14 occurred in 20 out of 32 informative cases (62.5%) by Southern analysis. Furthermore, PCR-LOH added three positive cases. Mobility shift by PCR-SSCP was observed in one case at exon 22, which showed 1 bp deletion in codon 771 of RB gene resulting in frame shift mutation. Besides, nine PCR-band alteration in tumor tissue compared with normal tissue were observed in exon 14 and 22, but mutation was not found on sequencing analysis suggesting the epigenetic alteration in tumor tissue. Analysis of the clinical data did not show any difference depending upon RB alteration. However, the total incidence of RB gene may play an important role in the development of esophageal cancer. The main genetic alteration of RB gene was deletion detected by Southern blot and one bp deletion leading to frame shift was also observed. 8 figs, 5 tabs. (Author).

  8. Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

    Science.gov (United States)

    Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

    2016-01-01

    The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

  9. Genetic alterations in B-cell non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Magić Zvonko

    2005-01-01

    Full Text Available Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL, 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL and 6 cases of chronic lymphadenitis (CL. The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT. Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34 of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6% B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled, K-ras mutations in 1/31 (3.23% and H-ras mutations in 2/31 (6.45% of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12 with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after

  10. DNA Fingerprinting Techniques for the Analysis of Genetic and Epigenetic Alterations in Colorectal Cancer

    OpenAIRE

    Samuelsson, Johanna K.; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-01-01

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in ca...

  11. A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Isabel Miranda

    Full Text Available BACKGROUND: The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG(Ser. We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations. METHODOLOGY/PRINCIPAL FINDINGS: We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. CONCLUSION/SIGNIFICANCE: Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes.

  12. Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

    Science.gov (United States)

    Lee, Min-Young; Ku, Bo Mi; Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se-Hoon; Park, Keunchil; Oh, Young Lyun; Hong, Mineui; Jeong, Han-Sin; Son, Young-Ik; Baek, Chung-Hwan; Ahn, Myung-Ju

    2017-10-01

    Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

  13. [Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain identification].

    Science.gov (United States)

    Smirnova, N I; Agafonov, D A; Zadnova, S P; Cherkasov, A V; Kutyrev, V V

    2014-01-01

    Development of an algorithm of genetically altered Vibrio cholerae biovar El Tor strai identification that ensures determination of serogroup, serovar and biovar of the studied isolate based on pheno- and genotypic properties, detection of genetically altered cholera El Tor causative agents, their differentiation by epidemic potential as well as evaluation of variability of key pathogenicity genes. Complex analysis of 28 natural V. cholerae strains was carried out by using traditional microbiological methods, PCR and fragmentary sequencing. An algorithm of toxigenic genetically altered V. cholerae biovar El Tor strain identification was developed that includes 4 stages: determination of serogroup, serovar and biovar based on phenotypic properties, confirmation of serogroup and biovar based on molecular-genetic properties determination of strains as genetically altered, differentiation of genetically altered strains by their epidemic potential and detection of ctxB and tcpA key pathogenicity gene polymorphism. The algorithm is based on the use of traditional microbiological methods, PCR and sequencing of gene fragments. The use of the developed algorithm will increase the effectiveness of detection of genetically altered variants of the cholera El Tor causative agent, their differentiation by epidemic potential and will ensure establishment of polymorphism of genes that code key pathogenicity factors for determination of origins of the strains and possible routes of introduction of the infection.

  14. Low Genetic Quality Alters Key Dimensions of the Mutational Spectrum.

    Directory of Open Access Journals (Sweden)

    Nathaniel P Sharp

    2016-03-01

    Full Text Available Mutations affect individual health, population persistence, adaptation, diversification, and genome evolution. There is evidence that the mutation rate varies among genotypes, but the causes of this variation are poorly understood. Here, we link differences in genetic quality with variation in spontaneous mutation in a Drosophila mutation accumulation experiment. We find that chromosomes maintained in low-quality genetic backgrounds experience a higher rate of indel mutation and a lower rate of gene conversion in a manner consistent with condition-based differences in the mechanisms used to repair DNA double strand breaks. These aspects of the mutational spectrum were also associated with body mass, suggesting that the effect of genetic quality on DNA repair was mediated by overall condition, and providing a mechanistic explanation for the differences in mutational fitness decline among these genotypes. The rate and spectrum of substitutions was unaffected by genetic quality, but we find variation in the probability of substitutions and indels with respect to several aspects of local sequence context, particularly GC content, with implications for models of molecular evolution and genome scans for signs of selection. Our finding that the chances of mutation depend on genetic context and overall condition has important implications for how sequences evolve, the risk of extinction, and human health.

  15. Somatic retrotransposition alters the genetic landscape of the human brain

    NARCIS (Netherlands)

    Baillie, J.K.; Barnett, M.W.; Upton, K.R.; Gerhardt, D.J.; Richmond, T.A.; De Sapio, F.; Brennan, P.; Rizzu, P.; Smith, S.; Fell, M.; Talbot, R.T.; Gustincich, S.; Freeman, T.C.; Mattick, J.S.; Hume, D.A.; Heutink, P.; Carninci, P.; Jeddeloh, J.A.; Faulkner, G.J.

    2011-01-01

    Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and

  16. How much do genetic covariances alter the rate of adaptation?

    Science.gov (United States)

    Agrawal, Aneil F; Stinchcombe, John R

    2009-03-22

    Genetically correlated traits do not evolve independently, and the covariances between traits affect the rate at which a population adapts to a specified selection regime. To measure the impact of genetic covariances on the rate of adaptation, we compare the rate fitness increases given the observed G matrix to the expected rate if all the covariances in the G matrix are set to zero. Using data from the literature, we estimate the effect of genetic covariances in real populations. We find no net tendency for covariances to constrain the rate of adaptation, though the quality and heterogeneity of the data limit the certainty of this result. There are some examples in which covariances strongly constrain the rate of adaptation but these are balanced by counter examples in which covariances facilitate the rate of adaptation; in many cases, covariances have little or no effect. We also discuss how our metric can be used to identify traits or suites of traits whose genetic covariances to other traits have a particularly large impact on the rate of adaptation.

  17. The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

    Directory of Open Access Journals (Sweden)

    Anna Abulí

    Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

  18. Aspen Delineation - Aspen Delineation Project [ds362

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of aspen stands, where aspen assessment data was gathered. Aspen assessment information corresponding to this polygon layer can...

  19. Critical roles for a genetic code alteration in the evolution of the genus Candida.

    Science.gov (United States)

    Silva, Raquel M; Paredes, João A; Moura, Gabriela R; Manadas, Bruno; Lima-Costa, Tatiana; Rocha, Rita; Miranda, Isabel; Gomes, Ana C; Koerkamp, Marian J G; Perrot, Michel; Holstege, Frank C P; Boucherie, Hélian; Santos, Manuel A S

    2007-10-31

    During the last 30 years, several alterations to the standard genetic code have been discovered in various bacterial and eukaryotic species. Sense and nonsense codons have been reassigned or reprogrammed to expand the genetic code to selenocysteine and pyrrolysine. These discoveries highlight unexpected flexibility in the genetic code, but do not elucidate how the organisms survived the proteome chaos generated by codon identity redefinition. In order to shed new light on this question, we have reconstructed a Candida genetic code alteration in Saccharomyces cerevisiae and used a combination of DNA microarrays, proteomics and genetics approaches to evaluate its impact on gene expression, adaptation and sexual reproduction. This genetic manipulation blocked mating, locked yeast in a diploid state, remodelled gene expression and created stress cross-protection that generated adaptive advantages under environmental challenging conditions. This study highlights unanticipated roles for codon identity redefinition during the evolution of the genus Candida, and strongly suggests that genetic code alterations create genetic barriers that speed up speciation.

  20. Genetic alterations affecting cholesterol metabolism and human fertility.

    Science.gov (United States)

    DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle

    2014-11-01

    Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.

  1. Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection

    Directory of Open Access Journals (Sweden)

    Gonzalo Castillo-Rojas

    2017-05-01

    Full Text Available Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, β-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3β, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2 have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.

  2. Analysis of Genetic Diversity of Two Mangrove Species with Morphological Alterations in a Natural Environment

    Directory of Open Access Journals (Sweden)

    Catarina Fonseca Lira-Medeiros

    2015-04-01

    Full Text Available Mangrove is an ecosystem subjected to tide, salinity and nutrient variations. These conditions are stressful to most plants, except to mangrove plants that are well-adapted. However, many mangrove areas have extremely stressful conditions, such as salt marshes, and the plants nearby usually present morphological alterations. In Sepetiba Bay, two species of mangrove plants, Avicennia schaueriana and Laguncularia racemosa, have poor development near a salt marsh (SM compared to plants at the riverside (RS, which is considered a favorable habitat in mangroves. The level of genetic diversity and its possible correlation with the morphological divergence of SM and RS plants of both species were assessed by AFLP molecular markers. We found moderate genetic differentiation between A. schaueriana plants from SM and RS areas and depleted genetic diversity on SM plants. On the other hand, Laguncularia racemosa plants had no genetic differentiation between areas. It is possible that a limited gene flow among the studied areas might be acting more intensely on A. schaueriana plants, resulting in the observed genetic differentiation. The populations of Laguncularia racemosa appear to be well connected, as genetic differentiation was not significant between the SM and RS populations. Gene flow and genetic drift are acting on neutral genetic diversity of these two mangrove species in the studied areas, and the observed genetic differentiation of A. schaueriana plants might be correlated with its morphological variation. For L. racemosa, morphological alterations could be related to epigenetic phenomena or adaptive loci polymorphism that should be further investigated.

  3. A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space.

    Directory of Open Access Journals (Sweden)

    Luis Zea

    Full Text Available Bacteria behave differently in space, as indicated by reports of reduced lag phase, higher final cell counts, enhanced biofilm formation, increased virulence, and reduced susceptibility to antibiotics. These phenomena are theorized, at least in part, to result from reduced mass transport in the local extracellular environment, where movement of molecules consumed and excreted by the cell is limited to diffusion in the absence of gravity-dependent convection. However, to date neither empirical nor computational approaches have been able to provide sufficient evidence to confirm this explanation. Molecular genetic analysis findings, conducted as part of a recent spaceflight investigation, support the proposed model. This investigation indicated an overexpression of genes associated with starvation, the search for alternative energy sources, increased metabolism, enhanced acetate production, and other systematic responses to acidity-all of which can be associated with reduced extracellular mass transport.

  4. A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space

    Science.gov (United States)

    Prasad, Nripesh; Levy, Shawn E.; Stodieck, Louis; Jones, Angela; Shrestha, Shristi; Klaus, David

    2016-01-01

    Bacteria behave differently in space, as indicated by reports of reduced lag phase, higher final cell counts, enhanced biofilm formation, increased virulence, and reduced susceptibility to antibiotics. These phenomena are theorized, at least in part, to result from reduced mass transport in the local extracellular environment, where movement of molecules consumed and excreted by the cell is limited to diffusion in the absence of gravity-dependent convection. However, to date neither empirical nor computational approaches have been able to provide sufficient evidence to confirm this explanation. Molecular genetic analysis findings, conducted as part of a recent spaceflight investigation, support the proposed model. This investigation indicated an overexpression of genes associated with starvation, the search for alternative energy sources, increased metabolism, enhanced acetate production, and other systematic responses to acidity—all of which can be associated with reduced extracellular mass transport. PMID:27806055

  5. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  6. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  7. Radiation as agents of somatic and genetic alterations

    International Nuclear Information System (INIS)

    de Eston, V.R.

    1975-01-01

    According to the report on ''The Effects on Population of Exposure to Low Levels of Ionizing Radiation,'' whether we regard a risk as acceptable or not depends on how avoidable it is, and, if not avoidable, how it compares with the risks of alternative options and those usually accepted by society. Regarding the use of ionizing radiation: No exposure should be permitted without the expectation of a commensurable benefit. The public must be protected from radiation, but not to the extent that the degree of protection provided results in the substitution of a worse hazard than that of the radiation avoided. Medical radiation exposure can and should be reduced considerably by limiting its use to clinically indicated procedures, utilizing efficient exposure techniques and optimal operation of radiation equipment. Consideration should be given to the following: (a) Restriction of the use of radiation for public health purposes, unless there is reasonable probability of significant detection of disease. (b) Inspection and licensing of radiation and ancillary equipment. (c) Appropriate training and certification of involved personnel. (d) Gonad shielding, especially shielding of the testis, is strongly recommended as a simple and highly efficient way to reduce the genetic significant dose. In a poignant phrase, Morgan has stated ''Radiation doesn't have to be feared, but should be respected.''

  8. Genetic and epigenetic alterations induced by different levels of rye genome integration in wheat recipient.

    Science.gov (United States)

    Zheng, X L; Zhou, J P; Zang, L L; Tang, A T; Liu, D Q; Deng, K J; Zhang, Y

    2016-06-17

    The narrow genetic variation present in common wheat (Triticum aestivum) varieties has greatly restricted the improvement of crop yield in modern breeding systems. Alien addition lines have proven to be an effective means to broaden the genetic diversity of common wheat. Wheat-rye addition lines, which are the direct bridge materials for wheat improvement, have been wildly used to produce new wheat cultivars carrying alien rye germplasm. In this study, we investigated the genetic and epigenetic alterations in two sets of wheat-rye disomic addition lines (1R-7R) and the corresponding triticales. We used expressed sequence tag-simple sequence repeat, amplified fragment length polymorphism, and methylation-sensitive amplification polymorphism analyses to analyze the effects of the introduction of alien chromosomes (either the entire genome or sub-genome) to wheat genetic background. We found obvious and diversiform variations in the genomic primary structure, as well as alterations in the extent and pattern of the genomic DNA methylation of the recipient. Meanwhile, these results also showed that introduction of different rye chromosomes could induce different genetic and epigenetic alterations in its recipient, and the genetic background of the parents is an important factor for genomic and epigenetic variation induced by alien chromosome addition.

  9. Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix

    NARCIS (Netherlands)

    Kersemaekers, A. M.; van de Vijver, M. J.; Kenter, G. G.; Fleuren, G. J.

    1999-01-01

    Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies

  10. The wild life at Chernobyl. Analysis of a prosperous but genetically altered fauna

    International Nuclear Information System (INIS)

    Chesser, R.; Baker, R.

    1996-01-01

    The ecological study of zones contaminated by Chernobyl accident reveals that the wild life abounds, because of inhabitants absence, evacuated. On the other hand, significant genetical alterations are observed, whom functional consequences, low visible, stay, at term, unknown. This kind of studies illustrates the development of a new discipline, the evolving toxicology

  11. DNA fingerprinting techniques for the analysis of genetic and epigenetic alterations in colorectal cancer.

    Science.gov (United States)

    Samuelsson, Johanna K; Alonso, Sergio; Yamamoto, Fumiichiro; Perucho, Manuel

    2010-11-10

    Genetic somatic alterations are fundamental hallmarks of cancer. In addition to point and other small mutations targeting cancer genes, solid tumors often exhibit aneuploidy as well as multiple chromosomal rearrangements of large fragments of the genome. Whether somatic chromosomal alterations and aneuploidy are a driving force or a mere consequence of tumorigenesis remains controversial. Recently it became apparent that not only genetic but also epigenetic alterations play a major role in carcinogenesis. Epigenetic regulation mechanisms underlie the maintenance of cell identity crucial for development and differentiation. These epigenetic regulatory mechanisms have been found substantially altered during cancer development and progression. In this review, we discuss approaches designed to analyze genetic and epigenetic alterations in colorectal cancer, especially DNA fingerprinting approaches to detect changes in DNA copy number and methylation. DNA fingerprinting techniques, despite their modest throughput, played a pivotal role in significant discoveries in the molecular basis of colorectal cancer. The aim of this review is to revisit the fingerprinting technologies employed and the oncogenic processes that they unveiled. 2010 Elsevier B.V. All rights reserved.

  12. Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner

    OpenAIRE

    Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai

    2016-01-01

    Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...

  13. Generation of Infectious Poliovirus with Altered Genetic Information from Cloned cDNA.

    Science.gov (United States)

    Bujaki, Erika

    2016-01-01

    The effect of specific genetic alterations on virus biology and phenotype can be studied by a great number of available assays. The following method describes the basic protocol to generate infectious poliovirus with altered genetic information from cloned cDNA in cultured cells.The example explained here involves generation of a recombinant poliovirus genome by simply replacing a portion of the 5' noncoding region with a synthetic gene by restriction cloning. The vector containing the full length poliovirus genome and the insert DNA with the known mutation(s) are cleaved for directional cloning, then ligated and transformed into competent bacteria. The recombinant plasmid DNA is then propagated in bacteria and transcribed to RNA in vitro before RNA transfection of cultured cells is performed. Finally, viral particles are recovered from the cell culture.

  14. Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

    DEFF Research Database (Denmark)

    Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing

    2018-01-01

    BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic......-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment....... alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME...

  15. Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

    Science.gov (United States)

    Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

    2013-05-05

    Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

  16. Phytoplasmal infection derails genetically preprogrammed meristem fate and alters plant architecture

    OpenAIRE

    Wei, Wei; Davis, Robert Edward; Nuss, Donald L.; Zhao, Yan

    2013-01-01

    In higher plants, the destiny of apical meristems (stem cells) is specific organogenesis, which determines the pattern of plant growth, and therefore morphotype and fertility. We found that bacterial infection can derail the meristems from their genetically preprogrammed destiny, altering plant morphogenesis. We identified four abnormal growth patterns, symptoms, in tomato infected with a cell wall-less bacterium, and found that each symptom corresponds to a distinct phase in meristem fate de...

  17. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis

    OpenAIRE

    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) act...

  18. Non-biased enrichment does not improve quantitative proteomic delineation of reovirus T3D-infected HeLa cell protein alterations

    Directory of Open Access Journals (Sweden)

    Jieyuan eJiang

    2012-09-01

    Full Text Available Mass spectrometry-based methods have allowed elucidation of alterations in complex proteomes, such as eukaryotic cells. Such studies have identified and measured relative abundances of thousands of host proteins after cells are infected with a virus. One of the potential limitations in such studies is that generally only the most abundant proteins are identified, leaving the deep richness of the cellular proteome largely unexplored. We differentially labeled HeLa cells with light and heavy stable isotopic forms of lysine and arginine (SILAC and infected cells with reovirus strain T3D. Cells were harvested at 24 hours post-infection. Heavy-labeled infected and light-labeled mock-infected cells were mixed together 1:1. Cells were then divided into cytosol and nuclear fractions and each fraction analyzed, both by standard 2D-HPLC/MS, and also after each fraction had been reacted with a random hexapeptide library (Proteominer® beads to attempt to enrich for low-abundance cellular proteins. A total of 2736 proteins were identified by 2 or more peptides at >99% confidence, of which 66 were significantly up-regulated and 67 were significantly down-regulated. Up-regulated proteins included those involved in antimicrobial and antiviral responses, GTPase activity, nucleotide binding, interferon signaling, and enzymes associated with energy generation. Down-regulated proteins included those involved in cell and biological adhesion, regulation of cell proliferation, structural molecule activity, and numerous molecular binding activities. Comparisons of the r2 correlations, degree of dataset overlap, and numbers of peptides detected suggest that non-biased enrichment approaches may not provide additional data to allow deeper quantitative and comparative mining of complex proteomes.

  19. Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

    Science.gov (United States)

    Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

    2016-04-07

    Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.

  20. Population genetic dynamics of three-spined sticklebacks (Gasterosteus aculeatus) in anthropogenic altered habitats.

    Science.gov (United States)

    Scharsack, Joern P; Schweyen, Hannah; Schmidt, Alexander M; Dittmar, Janine; Reusch, Thorsten Bh; Kurtz, Joachim

    2012-06-01

    In industrialized and/or agriculturally used landscapes, inhabiting species are exposed to a variety of anthropogenic changes in their environments. Genetic diversity may be reduced if populations encounter founder events, bottlenecks, or isolation. Conversely, genetic diversity may increase if populations adapt to changes in selective regimes in newly created habitats. With the present study, genetic variability of 918 sticklebacks from 43 samplings (21.3 ± 3.8 per sample) at 36 locations from cultivated landscapes in Northwest Germany was analyzed at nine neutral microsatellite loci. To test if differentiation is influenced by habitat alterations, sticklebacks were collected from ancient running waters and adjacent artificial stagnant waters, from brooks with salt water inflow of anthropogenic and natural origin and adjacent freshwater sites. Overall population structure was dominated by isolation by distance (IBD), which was significant across all populations, and analysis of molecular variance (AMOVA) revealed that 10.6% of the variation was explained by river catchment area. Populations in anthropogenic modified habitats deviated from the general IBD structure and in the AMOVA, grouping by habitat type running/stagnant water explained 4.9% of variation and 1.4% of the variation was explained by salt-/freshwater habitat. Sticklebacks in salt-polluted water systems seem to exhibit elevated migratory activity between fresh- and saltwater habitats, reducing IBD. In other situations, populations showed distinct signs of genetic isolation, which in some locations was attributed to mechanical migration barriers, but in others to potential anthropogenic induced bottleneck or founder effects. The present study shows that anthropogenic habitat alterations may have diverse effects on the population genetic structure of inhabiting species. Depending on the type of habitat change, increased genetic differentiation, diversification, or isolation are possible consequences.

  1. Introgression from cultivated rice alters genetic structures of wild relative populations: implications for in situ conservation

    Science.gov (United States)

    Jin, Xin; Chen, Yu; Liu, Ping; Li, Chen; Cai, Xingxing; Rong, Jun

    2018-01-01

    Abstract Maintaining genetic integrity is essential for in situ and ex situ conservation of crop wild relative (CWR) species. However, introgression of crop alleles into CWR species/populations may change their genetic structure and diversity, resulting in more invasive weeds or, in contrast, the extinction of endangered populations. To determine crop-wild introgression and its consequences, we examined the genetic structure and diversity of six wild rice (Oryza rufipogon) populations under in situ conservation in China. Thirty-four simple sequence repeat (SSR) and 34 insertion/deletion markers were used to genotype the wild rice populations and two sets of rice cultivars (O. sativa), corresponding to the two types of molecular markers. Shared alleles and STRUCTURE analyses suggested a variable level of crop-wild introgression and admixture. Principal coordinates and cluster analyses indicated differentiation of wild rice populations, which was associated with the spatial distances to cultivated rice fields. The level of overall genetic diversity was comparable between wild rice populations and rice cultivars, but a great number of wild-specific alleles was detected in the wild populations. We conclude based on the results that crop-wild introgression can considerably alter the pattern of genetic structure and relationships of CWR populations. Appropriate measures should be taken for effective in situ conservation of CWR species under the scenario of crop-wild introgression. PMID:29308123

  2. Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

    Science.gov (United States)

    Choi, Woonyoung; Ochoa, Andrea; McConkey, David J; Aine, Mattias; Höglund, Mattias; Kim, William Y; Real, Francisco X; Kiltie, Anne E; Milsom, Ian; Dyrskjøt, Lars; Lerner, Seth P

    2017-09-01

    Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  3. Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease.

    Directory of Open Access Journals (Sweden)

    Katrina Soderquest

    2017-02-01

    Full Text Available The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21 specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn's disease, ulcerative colitis (UC and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner.

  4. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, I.B.; Worm, J.; Ralfkiaer, E.

    2008-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, w...... with adverse outcome. In DLBCL, genetic and epigenetic alterations of RFC were detected at diagnosis in the absence of a selective MTX pressure, suggesting that these alterations may possibly contribute to the development of lymphoma Udgivelsesdato: 2008/1...

  5. Production of extracellular nucleic acids by genetically altered bacteria in aquatic-environment microcosms

    International Nuclear Information System (INIS)

    Paul, J.H.; David, A.W.

    1989-01-01

    The factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated. Cellular nucleic acids were labeled in vivo by incubation with [ 3 H]thymidine or [ 3 H]adenine, and production of extracellular DNA in marine waters, artificial seawater, or minimal salts media was determined by detecting radiolabeled macromolecules in incubation filtrates. The presence or absence of the ambient microbial community had little effect on the production of extracellular DNA. Three of four organisms produced the greatest amounts of extracellular nucleic acids when incubated in low-salinity media (2% artificial seawater) rather than high-salinity media (10 to 50% artificial seawater). The greatest production of extracellular nucleic acids by P. cepacia occurred at pH 7 and 37 degree C, suggesting that extracellular-DNA production may be a normal physiologic function of the cell. Incubation of labeled P. cepacia cells in water from Bimini Harbor, Bahamas, resulted in labeling of macromolecules of the ambient microbial population. Collectively these results indicate that (i) extracellular-DNA production by genetically altered bacteria released into aquatic environments is more strongly influenced by physicochemical factors than biotic factors, (ii) extracellular-DNA production rates are usually greater for organisms released in freshwater than marine environments, and (iii) ambient microbial populations can readily utilize materials released by these organisms

  6. The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

    Science.gov (United States)

    Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

    2018-02-28

    Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

  7. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  8. A novel nuclear genetic code alteration in yeasts and the evolution of codon reassignment in eukaryotes.

    Science.gov (United States)

    Mühlhausen, Stefanie; Findeisen, Peggy; Plessmann, Uwe; Urlaub, Henning; Kollmar, Martin

    2016-07-01

    The genetic code is the cellular translation table for the conversion of nucleotide sequences into amino acid sequences. Changes to the meaning of sense codons would introduce errors into almost every translated message and are expected to be highly detrimental. However, reassignment of single or multiple codons in mitochondria and nuclear genomes, although extremely rare, demonstrates that the code can evolve. Several models for the mechanism of alteration of nuclear genetic codes have been proposed (including "codon capture," "genome streamlining," and "ambiguous intermediate" theories), but with little resolution. Here, we report a novel sense codon reassignment in Pachysolen tannophilus, a yeast related to the Pichiaceae. By generating proteomics data and using tRNA sequence comparisons, we show that Pachysolen translates CUG codons as alanine and not as the more usual leucine. The Pachysolen tRNACAG is an anticodon-mutated tRNA(Ala) containing all major alanine tRNA recognition sites. The polyphyly of the CUG-decoding tRNAs in yeasts is best explained by a tRNA loss driven codon reassignment mechanism. Loss of the CUG-tRNA in the ancient yeast is followed by gradual decrease of respective codons and subsequent codon capture by tRNAs whose anticodon is not part of the aminoacyl-tRNA synthetase recognition region. Our hypothesis applies to all nuclear genetic code alterations and provides several testable predictions. We anticipate more codon reassignments to be uncovered in existing and upcoming genome projects. © 2016 Mühlhausen et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Parkinson's disease and pesticides: A meta-analysis of disease connection and genetic alterations.

    Science.gov (United States)

    Ahmed, Hussien; Abushouk, Abdelrahman Ibrahim; Gabr, Mohamed; Negida, Ahmed; Abdel-Daim, Mohamed M

    2017-06-01

    Parkinson's disease (PD) is a globally prevalent, multifactorial disorder that occurs due to interactions between genetic and environmental factors. Observational studies have shown a link between exposure to pesticides and the risk of PD. We performed this study to systemically review published case-control studies and estimate quantitatively the association between pesticide exposure and PD. We searched Medline (through PubMed) for eligible case-control studies. The association between pesticide exposure and PD risk or occurrence of certain genetic alterations, related to the pathogenesis of PD was presented as odds ratios (OR) and pooled under the random effects model, using the statistical add-in (MetaXL, version 5.0). The pooled result showed that exposure to pesticides is linked to PD (OR 1.46, 95% CI [1.21, 1.77]), but there was a significant heterogeneity among included studies. Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]). There was no statistically significant association between exposure to pesticides and alteration of CYP2D6 (OR 1.19, 95% CI [0.91, 1.54]), SLC6A3 (OR 0.74, 95% CI [0.55, 1]), MnSOD (OR 1.45, 95% CI [0.97, 2.16]), NQO1 (OR 1.35, 95% CI [0.91, 2.01]), and PON-2 genes (OR 0.88, 95% CI [0.53, 1.45]). In conclusion, this meta-analysis provides evidence that pesticide exposure is significantly associated with the risk of PD and alterations in genes involved in PD pathogenesis. However, the underlying mechanism of this association and the effect of the duration of exposure or the type of pesticides should be addressed by future research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Transforming growth factor-β and breast cancer: Lessons learned from genetically altered mouse models

    International Nuclear Information System (INIS)

    Wakefield, Lalage M; Yang, Yu-an; Dukhanina, Oksana

    2000-01-01

    Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development

  11. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases.

    Science.gov (United States)

    Zhou, Yan; Proudnikov, Dmitri; Yuferov, Vadim; Kreek, Mary Jeanne

    2010-02-16

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and resultant changes in hormone levels, have been documented to occur after chronic intermittent exposure to heroin, morphine, other opiates, cocaine, other stimulants, and alcohol in animal models and in human molecular genetics. The best studied of the stress-responsive systems in humans and mammalian species in general is undoubtedly the HPA axis. In addition, there are stress-responsive systems in other parts in the brain itself, and some of these include components of the HPA axis, such as CRF and CRF receptors, along with POMC gene and gene products. Several other stress-responsive systems are known to influence the HPA axis, such as the vasopressin-vasopressin receptor system. Orexin-hypocretin, acting at its receptors, may effect changes which suggest that it should be properly categorized as a stress-responsive system. However, less is known about the interactions and connectivity of some of these different neuropeptide and receptor systems, and in particular, about the possible connectivity of fast-acting (e.g., glutamate and GABA) and slow-acting (including dopamine, serotonin, and norepinephrine) neurotransmitters with each of these stress-responsive components and the resultant impact, especially in the setting of chronic exposure to drugs of abuse. Several of these stress-responsive systems and components, primarily based on our laboratory-based and human molecular genetics research of addictive diseases, will be briefly discussed in this review. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Targeted molecular profiling of rare genetic alterations in colorectal cancer using next-generation sequencing.

    Science.gov (United States)

    Jauhri, Mayank; Bhatnagar, Akanksha; Gupta, Satish; Shokeen, Yogender; Minhas, Sachin; Aggarwal, Shyam

    2016-10-01

    Mutation frequencies of common genetic alterations in colorectal cancer have been in the spotlight for many years. This study highlights few rare somatic mutations, which possess the attributes of a potential CRC biomarker yet are often neglected. Next-generation sequencing was performed over 112 tumor samples to detect genetic alterations in 31 rare genes in colorectal cancer. Mutations were detected in 26/31 (83.9 %) uncommon genes, which together contributed toward 149 gene mutations in 67/112 (59.8 %) colorectal cancer patients. The most frequent mutations include KDR (19.6 %), PTEN (17 %), FBXW7 (10.7 %), SMAD4 (10.7 %), VHL (8 %), KIT (8 %), MET (7.1 %), ATM (6.3 %), CTNNB1 (4.5 %) and CDKN2A (4.5 %). RB1, ERBB4 and ERBB2 mutations were persistent in 3.6 % patients. GNAS, FGFR2 and FGFR3 mutations were persistent in 1.8 % patients. Ten genes (EGFR, NOTCH1, SMARCB1, ABL1, STK11, SMO, RET, GNAQ, CSF1R and FLT3) were found mutated in 0.9 % patients. Lastly, no mutations were observed in AKT, HRAS, MAP2K1, PDGFR and JAK2. Significant associations were observed between VHL with tumor site, ERBB4 and SMARCB1 with tumor invasion, CTNNB1 with lack of lymph node involvement and CTNNB1, FGFR2 and FGFR3 with TNM stage. Significantly coinciding mutation pairs include PTEN and SMAD4, PTEN and KDR, EGFR and RET, EGFR and RB1, FBXW7 and CTNNB1, KDR and FGFR2, FLT3 and CTNNB1, RET and RB1, ATM and SMAD4, ATM and CDKN2A, ERBB4 and SMARCB1. This study elucidates few potential colorectal cancer biomarkers, specifically KDR, PTEN, FBXW7 and SMAD4, which are found mutated in more than 10 % patients.

  13. Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population.

    Science.gov (United States)

    Wei, Hui; Wang, Ying; Zhou, Chunlin; Lin, Dong; Liu, Bingcheng; Liu, Kaiqi; Qiu, Shaowei; Gong, Benfa; Li, Yan; Zhang, Guangji; Wei, Shuning; Gong, Xiaoyuan; Liu, Yuntao; Zhao, Xingli; Gu, Runxia; Mi, Yingchang; Wang, Jianxiang

    2018-02-10

    Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.

  14. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Science.gov (United States)

    Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

    2005-01-01

    AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

  15. Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.

    Science.gov (United States)

    Plo, Isabelle; Bellanné-Chantelot, Christine; Mosca, Matthieu; Mazzi, Stefania; Marty, Caroline; Vainchenker, William

    2017-01-01

    Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity ( MPL, JAK2, CALR ) and loss-of-function (LOF) activity of negative regulators ( CBL, LNK ) or the extrinsic MPL signaling by THPO GOF mutations leading to increased TPO synthesis. Alternatively, thrombocytosis may paradoxically result from mutations of MPL leading to an abnormal MPL trafficking, inducing increased TPO levels by alteration of its clearance. In contrast, thrombocytopenia can also result from LOF THPO or MPL mutations, which cause a complete defect in MPL trafficking to the cell membrane, impaired MPL signaling or stability, defects in the TPO/MPL interaction, or an absence of TPO production.

  16. Genetic alterations in lung cancer: Assessing limitations in routine clinical use

    Directory of Open Access Journals (Sweden)

    Joana Espiga Macedo

    2007-01-01

    Full Text Available Lung cancer is the most frequent cause of cancer mortality worldwide, responsible for approximately 1.1 million deaths per year. Median survival is short, both as most tumours are diagnosed at an advanced stage and because of the limited efficacy of available treatments. The development of tumour molecular genetics carries the promise of altering this state of affairs, as it should lead to a more precise classification of tumours, identify specific molecular targets for therapy and, above all, allow the development of new methods for early diagnosis. Despite numerous studies demonstrating the usefulness of molecular genetic techniques in the study of lung cancer, its routine clinical use in Portugal has, however, been limited.In this study, we used a p53 mutation screen in multiple clinical samples from a series of lung cancer patients to attempt to identify the main practical limitations to the integration of molecular genetics in routine clinical practice. Our results suggest that the main limiting factor is the availability of samples with good quality DNA; a problem that could be overcome by alterations in common sample collection and storage procedures. Resumo: O cancro do pulmão é a causa mais frequente de mortalidade por cancro no mundo, sendo responsável por cerca de 1,1 milhões de mortes por ano. A sobrevivência média dos doentes é geralmente curta, por a doença se encontrar em estádios avançados na altura do diagnóstico, mas também devido à falta de eficácia dos tratamentos disponíveis. O advento da genética molecular dos tumores trouxe consigo a possibilidade de modificar esta situação, quer através do refinamento do diagnóstico, quer da identificação de alvos terapêuticos específicos, quer sobretudo por – pelo menos em teoria – permitir o diagnóstico precoce da doença. No entanto, e apesar de numerosos trabalhos terem já demonstrado a utilidade

  17. Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Stine H Kresse

    Full Text Available BACKGROUND: Osteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression using a recurrence threshold of 6/19 (>30% cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between

  18. Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation.

    Science.gov (United States)

    Hasumi, Hisashi; Yao, Masahiro

    2018-03-01

    Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, USA and the first kidney cancer-associated gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL) syndrome in 1993. Subsequent molecular studies on VHL function have elucidated that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia-inducible factor (HIF), which provided the basis for the development of tyrosine kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer-associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. Experimental pavement delineation treatments

    Science.gov (United States)

    Bryden, J. E.; Lorini, R. A.

    1981-06-01

    Visibility and durability of materials used to delineate shoulders and medians adjacent to asphalt pavements were evaluated. Materials evaluated were polysulfide and coal tar epoxies, one and two component polyesters, portland cement, acrylic paints, modified-alkyd traffic paint, preformed plastic tape, and thermoplastic markings. Neat applications, sand mortars, and surface treatments were installed in several geometric patterns including cross hatches, solid median treatments, and various widths of edge lines. Thermoplastic pavement markings generally performed very well, providing good visibility under adverse viewing conditions for at least 4 years. Thermoplastic 4 in. wide edge lines appear to provide adequate visibility for most conditions.

  20. SNPs selected by information content outperform randomly selected microsatellite loci for delineating genetic identification and introgression in the endangered dark European honeybee (Apis mellifera mellifera).

    Science.gov (United States)

    Muñoz, Irene; Henriques, Dora; Jara, Laura; Johnston, J Spencer; Chávez-Galarza, Julio; De La Rúa, Pilar; Pinto, M Alice

    2017-07-01

    The honeybee (Apis mellifera) has been threatened by multiple factors including pests and pathogens, pesticides and loss of locally adapted gene complexes due to replacement and introgression. In western Europe, the genetic integrity of the native A. m. mellifera (M-lineage) is endangered due to trading and intensive queen breeding with commercial subspecies of eastern European ancestry (C-lineage). Effective conservation actions require reliable molecular tools to identify pure-bred A. m. mellifera colonies. Microsatellites have been preferred for identification of A. m. mellifera stocks across conservation centres. However, owing to high throughput, easy transferability between laboratories and low genotyping error, SNPs promise to become popular. Here, we compared the resolving power of a widely utilized microsatellite set to detect structure and introgression with that of different sets that combine a variable number of SNPs selected for their information content and genomic proximity to the microsatellite loci. Contrary to every SNP data set, microsatellites did not discriminate between the two lineages in the PCA space. Mean introgression proportions were identical across the two marker types, although at the individual level, microsatellites' performance was relatively poor at the upper range of Q-values, a result reflected by their lower precision. Our results suggest that SNPs are more accurate and powerful than microsatellites for identification of A. m. mellifera colonies, especially when they are selected by information content. © 2016 John Wiley & Sons Ltd.

  1. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  2. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches.

    Directory of Open Access Journals (Sweden)

    Ruben Perez-Carrasco

    2016-10-01

    Full Text Available During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can

  3. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    Science.gov (United States)

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  4. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity.

    Directory of Open Access Journals (Sweden)

    Konstantin V Salojin

    Full Text Available Mammalian sterile 20-like kinase 1 (Mst1 is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4+ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1-/- B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE and protected against collagen-induced arthritis development. Mst1-/- CD4+ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4+ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.

  5. Harnessing genomics for delineating conservation units.

    Science.gov (United States)

    Funk, W Chris; McKay, John K; Hohenlohe, Paul A; Allendorf, Fred W

    2012-09-01

    Genomic data have the potential to revolutionize the delineation of conservation units (CUs) by allowing the detection of adaptive genetic variation, which is otherwise difficult for rare, endangered species. In contrast to previous recommendations, we propose that the use of neutral versus adaptive markers should not be viewed as alternatives. Rather, neutral and adaptive markers provide different types of information that should be combined to make optimal management decisions. Genetic patterns at neutral markers reflect the interaction of gene flow and genetic drift that affects genome-wide variation within and among populations. This population genetic structure is what natural selection operates on to cause adaptive divergence. Here, we provide a new framework to integrate data on neutral and adaptive markers to protect biodiversity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Sequential versus simultaneous market delineation

    DEFF Research Database (Denmark)

    Haldrup, Niels; Møllgaard, Peter; Kastberg Nielsen, Claus

    2005-01-01

    and geographical markets. Using a unique data setfor prices of Norwegian and Scottish salmon, we propose a methodologyfor simultaneous market delineation and we demonstrate that comparedto a sequential approach conclusions will be reversed.JEL: C3, K21, L41, Q22Keywords: Relevant market, econometric delineation......Delineation of the relevant market forms a pivotal part of most antitrustcases. The standard approach is sequential. First the product marketis delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographicaldimension...

  7. Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat.

    Science.gov (United States)

    Shitsukawa, Naoki; Tahira, Chikako; Kassai, Ken-Ichiro; Hirabayashi, Chizuru; Shimizu, Tomoaki; Takumi, Shigeo; Mochida, Keiichi; Kawaura, Kanako; Ogihara, Yasunari; Murai, Koji

    2007-06-01

    Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms.

  8. Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

    Science.gov (United States)

    Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

    2014-11-01

    The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Implications of Genetic and Epigenetic Alterations of CDKN2A (p16INK4a in Cancer

    Directory of Open Access Journals (Sweden)

    Ran Zhao

    2016-06-01

    Full Text Available Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

  10. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels.

    Directory of Open Access Journals (Sweden)

    Kate Lykke Lambertsen

    Full Text Available The calmodulin/calcium-activated K(+ channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice.In the open field test, KCa3.1-deficiency increased horizontal activity, as KCa3.1(-/- mice travelled longer distances (≈145% of KCa3.1(+/+ and at higher speed (≈1.5-fold of KCa3.1(+/+. Working memory in the Y-maze was reduced by KCa3.1-deficiency. Motor coordination on the rotarod and neuromuscular functions were unchanged. In KCa3.1(-/- mice, HPLC analysis revealed that turn-over rates of serotonin were reduced in frontal cortex, striatum and brain stem, while noradrenalin turn-over rates were increased in the frontal cortex. Dopamine turn-over rates were unaltered. Plasma catecholamine and corticosterone levels were unaltered. Intraperitoneal injections of 10 mg/kg of the KCa3.1/KCa2-activator SKA-31 reduced rearing and turning behavior in KCa3.1(+/+ but not in KCa3.1(-/- mice, while 30 mg/kg SKA-31 caused strong sedation in 50% of the animals of either genotypes. KCa3.1(-/- mice were hyperactive (≈+60% in their home cage and SKA-31-administration reduced nocturnal physical activity in KCa3.1(+/+ but not in KCa3.1(-/- mice.KCa3.1-deficiency causes locomotor hyperactivity and altered monoamine levels in selected brain regions, suggesting a so far unknown functional link of KCa3.1 channels to behavior and monoaminergic neurotransmission in mice. The tranquilizing effects of low-dose SKA-31 raise the possibility to use KCa3.1/KCa2 channels as novel pharmacological targets for the treatment of neuropsychiatric hyperactivity disorders.

  11. DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chun-Mei; Kwan, Johnson; Baumgartner, Adolf; Weier, Jingly F.; Wang, Mei; Escudero, Tomas; Munne' , Santiago; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich

    2009-01-30

    Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome (BAC) clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multi-clone and multi-color mapping experiments do not generate additional information. Our pooling protocol described here with examples from thyroid cancer research and PGD accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as three to four days.

  12. Macro-environment of breast carcinoma: frequent genetic alterations in the normal appearing skins of patients with breast cancer.

    Science.gov (United States)

    Moinfar, Farid; Beham, Alfred; Friedrich, Gerhard; Deutsch, Alexander; Hrzenjak, Andelko; Luschin, Gero; Tavassoli, Fattaneh A

    2008-05-01

    Genetic abnormalities in microenvironmental tissues with subsequent alterations of reciprocal interactions between epithelial and mesenchymal cells play a key role in the breast carcinogenesis. Although a few reports have demonstrated abnormal fibroblastic functions in normal-appearing fibroblasts taken from the skins of breast cancer patients, the genetic basis of this phenomenon and its implication for carcinogenesis are unexplored. We analyzed 12 mastectomy specimens showing invasive ductal carcinomas. In each case, morphologically normal epidermis and dermis, carcinoma, normal stroma close to carcinoma, and stroma at a distant from carcinoma were microdissected. Metastatic-free lymphatic tissues from lymph nodes served as a control. Using PCR, DNA extracts were examined with 11 microsatellite markers known for a high frequency of allelic imbalances in breast cancer. Losses of heterozygosity and/or microsatellite instability were detected in 83% of the skin samples occurring either concurrently with or independently from the cancerous tissues. In 80% of these cases at least one microsatellite marker displayed loss of heterozygosity or microsatellite instability in the skin, which was absent in carcinoma. A total of 41% of samples showed alterations of certain loci observed exclusively in the carcinoma but not in the skin compartments. Our study suggests that breast cancer is not just a localized genetic disorder, but rather part of a larger field of genetic alterations/instabilities affecting multiple cell populations in the organ with various cellular elements, ultimately contributing to the manifestation of the more 'localized' carcinoma. These data indicate that more global assessment of tumor micro- and macro-environment is crucial for our understanding of breast carcinogenesis.

  13. The genetic alteration of MTS1/CDKN2 gene in esophageal cancer

    International Nuclear Information System (INIS)

    Zo, Jae Ill; Paik, Hee Jong; Park, Jong Ho; Kim, Mi Hee

    1996-12-01

    MTS1/CDKN2 gene plays a key role in cell cycle regulation, and there have been many studies about the significance of this gene in tumorigenesis. To investigate the frequency of MTS1/CDKN2 gene alteration in Korean esophageal cancer, we studied 36 esophageal cancer tissues with paired PCR analysis to detect homozygous deletion and PCR-SSCP methods to find minute mutations, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. And in cases without RB gene a alterations, direct sequence analysis was also done. There was no homozygous deletions. Mobility shift by PCR-SSCP was observed in four cases at exon 2, which showed 1 bp deletion in codon 97 of mutation in codon 100 which changed TAT (Tyr) from GAT (Asp). But there were not MTS1/CDKN2 gene alterations in cases without Rb gene alterations. Analysis of clinical data did not show any differences depending upon MTS1/CDKN2 gene alterations. Therefore the MTS1/CDKN2 gene mutations were infrequent events and do not play a major role in the group of patients examined. More study for contribution of methylation in MTS1/CDKN2 gene for inactivation of p16 should be done before evaluation and application of MTS1/CDKN2 gene in tumorigenesis and as an candidate of gene therapy. (author). 15 refs

  14. The genetic alteration of MTS1/CDKN2 gene in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zo, Jae Ill; Paik, Hee Jong; Park, Jong Ho; Kim, Mi Hee [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-12-01

    MTS1/CDKN2 gene plays a key role in cell cycle regulation, and there have been many studies about the significance of this gene in tumorigenesis. To investigate the frequency of MTS1/CDKN2 gene alteration in Korean esophageal cancer, we studied 36 esophageal cancer tissues with paired PCR analysis to detect homozygous deletion and PCR-SSCP methods to find minute mutations, if any. In the cases with abnormalities, the nucleotide sequence analysis was performed. And in cases without RB gene a alterations, direct sequence analysis was also done. There was no homozygous deletions. Mobility shift by PCR-SSCP was observed in four cases at exon 2, which showed 1 bp deletion in codon 97 of mutation in codon 100 which changed TAT (Tyr) from GAT (Asp). But there were not MTS1/CDKN2 gene alterations in cases without Rb gene alterations. Analysis of clinical data did not show any differences depending upon MTS1/CDKN2 gene alterations. Therefore the MTS1/CDKN2 gene mutations were infrequent events and do not play a major role in the group of patients examined. More study for contribution of methylation in MTS1/CDKN2 gene for inactivation of p16 should be done before evaluation and application of MTS1/CDKN2 gene in tumorigenesis and as an candidate of gene therapy. (author). 15 refs.

  15. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations

    Directory of Open Access Journals (Sweden)

    Ariel B. Ganz

    2017-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75 consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9 for 10–12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

  16. Y chromosome microdeletions and alterations of spermatogenesis, patient approach and genetic counseling.

    Science.gov (United States)

    Rives, Nathalie

    2014-05-01

    Infertility affects 15% of couples at reproductive age and human male infertility appears frequently idiopathic. The main genetic causes of spermatogenesis defect responsible for non-obstructive azoospermia and severe oligozoospermia are constitutional chromosomal abnormalities and microdeletions in the azoospermia factor region of the Y chromosome. The improvement of the Yq microdeletion screening method gave new insights in the mechanism responsible for the genesis of Yq microdeletions and for the consequences of the management of male infertility and genetic counselling in case of assisted reproductive technology. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Temporal organization of feeding in Syrian hamsters with a genetically altered circadian period

    NARCIS (Netherlands)

    Oklejewicz, M; Overkamp, GJF; Stirland, JA; Daan, S

    2001-01-01

    The variation in spontaneous meal patterning was studied in three genotypes (tau +/+, tau +/- and tau -/-) of the Syrian hamster with an altered circadian period. Feeding activity was monitored continuously in 13 individuals from each genotype in constant dim light conditions. All three genotypes

  18. Genetic KCa3.1-deficiency produces locomotor hyperactivity and alterations in cerebral monoamine levels

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Gramsbergen, Jan Bert; Sivasaravanaparan, Mithula

    2012-01-01

    The calmodulin/calcium-activated K(+) channel KCa3.1 is expressed in red and white blood cells, epithelia and endothelia, and possibly central and peripheral neurons. However, our knowledge about its contribution to neurological functions and behavior is incomplete. Here, we investigated whether...... genetic deficiency or pharmacological activation of KCa3.1 change behavior and cerebral monoamine levels in mice....

  19. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Chen, T-C; Hou, H-A; Chou, W-C; Tang, J-L; Kuo, Y-Y; Chen, C-Y; Tseng, M-H; Huang, C-F; Lai, Y-J; Chiang, Y-C; Lee, F-Y; Liu, M-C; Liu, C-W; Liu, C-Y; Yao, M; Huang, S-Y; Ko, B-S; Hsu, S-C; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2014-01-01

    Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression

  20. Altering BDNF expression by genetics and/or environment: impact for emotional and depression-like behaviour in laboratory mice.

    Science.gov (United States)

    Chourbaji, Sabine; Brandwein, Christiane; Gass, Peter

    2011-01-01

    According to the "neurotrophin hypothesis", brain-derived neurotrophic factor (BDNF) is an important candidate gene in depression. Moreover, environmental stress is known to represent a risk factor in the pathophysiology and treatment of this disease. To elucidate, whether changes of BDNF availability signify cause or consequence of depressive-like alterations, it is essential to look for endophenotypes under distinct genetic conditions (e.g. altered BDNF expression). Furthermore it is crucial to examine environment-driven BDNF regulation and its effect on depressive-linked features. Consequently, gene × environment studies investigating prospective genetic mouse models of depression in different environmental contexts become increasingly important. The present review summarizes recent findings in BDNF-mutant mice, which have been controversially discussed as models of depression and anxiety. It furthermore illustrates the potential of environment to serve as naturalistic stressor with the potential to modulate the phenotype in wildtype and mutant mice. Moreover, environment may exert protective effects by regulating BDNF levels as attributed to "environmental enrichment". The effect of this beneficial condition will also be discussed with regard to probable "curative/therapeutic" approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Genetic Alterations within the DENND1A Gene in Patients with Polycystic Ovary Syndrome (PCOS)

    DEFF Research Database (Denmark)

    Eriksen, Mette B; Nielsen, Michael F B; Brusgaard, Klaus

    2013-01-01

    sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C), potentially altering......Polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs) in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene...... and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one patient...

  2. Flight initiation and maintenance deficits in flies with genetically altered biogenic amine levels

    OpenAIRE

    Brembs, Björn; Christiansen, F.; Pflüger, J.; Duch, C.

    2007-01-01

    Insect flight is one of the fastest, most intense and most energy-demanding motor behaviors. It is modulated on multiple levels by the biogenic amine octopamine. Within the CNS, octopamine acts directly on the flight central pattern generator, and it affects motivational states. In the periphery, octopamine sensitizes sensory receptors, alters muscle contraction kinetics, and enhances flight muscle glycolysis. This study addresses the roles for octopamine and its precursor tyramine in flight ...

  3. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    Directory of Open Access Journals (Sweden)

    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  4. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Science.gov (United States)

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  5. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    Science.gov (United States)

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  6. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Tariq Waseem Chohan

    2014-09-01

    Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.

  7. Genetic alterations within the DENND1A gene in patients with polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Mette B Eriksen

    Full Text Available Polycystic ovary syndrome (PCOS, the most common endocrine disease among premenopausal women, is caused by both genes and environment. We and others previously reported association between single nucleotide polymorphisms (SNPs in the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white patients with PCOS to identify possible alterations that may be implicated in the PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998 and 2011 (n = 261. PCOS was diagnosed according to the Rotterdam criteria (n = 165. Sequence analysis was performed in 10 patients with PCOS. Additional patients (n = 251 and healthy female controls (n = 248 were included for SNP genotyping. Patients underwent clinical examination including Ferriman-Gallwey score (FG-score, biochemical analyses and transvaginal ultrasound. Mutation analysis was carried out by bidirectional sequencing. SNP genotyping was tested by allelic discrimination in real-time PCR in the additional patients and controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not known to be associated with any diseases. One missense SNP was detected (rs189947178, A/C, potentially altering the structural conformation of the DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers among patients with PCOS and moderate hirsutism compared to controls. However, due to small sample size and lack of multiple regression analysis supporting an association between rs189947178 and FG-score or PCOS diagnosis, this could be a false positive finding. In conclusion, sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis, but a missense SNP (rs189947178 was identified in one patient and significantly more carriers of rs189947178 were found among patients with PCOS and moderate hirsutism vs. controls. Additional studies with independent cohort are needed

  8. Assessing glycolytic flux alterations resulting from genetic perturbations in E. coli using a biosensor

    DEFF Research Database (Denmark)

    Lehning, Christina Eva; Siedler, Solvej; Ellabaan, Mostafa M Hashim

    2017-01-01

    validated the glycolytic flux dependency of the biosensor in a range of different carbon sources in six different E. coli strains and during mevalonate production. Furthermore, we studied the flux-altering effects of genome-wide single gene knock-outs in E. coli in a multiplex FlowSeq experiment. From...... a library consisting of 2126 knock-out mutants, we identified 3 mutants with high-flux and 95 mutants with low-flux phenotypes that did not have severe growth defects. This approach can improve our understanding of glycolytic flux regulation improving metabolic models and engineering efforts....

  9. 30 CFR 282.22 - Delineation Plan.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Delineation Plan. 282.22 Section 282.22 Mineral... § 282.22 Delineation Plan. All exploration activities shall be conducted in accordance with a Delineation Plan submitted by the lessee and approved by the Director. The Delineation Plan shall describe the...

  10. Delineating SPTAN1 associated phenotypes

    DEFF Research Database (Denmark)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena

    2017-01-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutati...

  11. Alteration of Box-Jenkins methodology by implementing genetic algorithm method

    Science.gov (United States)

    Ismail, Zuhaimy; Maarof, Mohd Zulariffin Md; Fadzli, Mohammad

    2015-02-01

    A time series is a set of values sequentially observed through time. The Box-Jenkins methodology is a systematic method of identifying, fitting, checking and using integrated autoregressive moving average time series model for forecasting. Box-Jenkins method is an appropriate for a medium to a long length (at least 50) time series data observation. When modeling a medium to a long length (at least 50), the difficulty arose in choosing the accurate order of model identification level and to discover the right parameter estimation. This presents the development of Genetic Algorithm heuristic method in solving the identification and estimation models problems in Box-Jenkins. Data on International Tourist arrivals to Malaysia were used to illustrate the effectiveness of this proposed method. The forecast results that generated from this proposed model outperformed single traditional Box-Jenkins model.

  12. Genetic and Epigenetic Alterations of Brassica nigra Introgression Lines from Somatic Hybridization: A Resource for Cauliflower Improvement.

    Science.gov (United States)

    Wang, Gui-Xiang; Lv, Jing; Zhang, Jie; Han, Shuo; Zong, Mei; Guo, Ning; Zeng, Xing-Ying; Zhang, Yue-Yun; Wang, You-Ping; Liu, Fan

    2016-01-01

    Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower "Korso" (Brassica oleracea var. botrytis, 2n = 18, CC genome) and black mustard "G1/1" (Brassica nigra, 2n = 16, BB genome). However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs) were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits) and physiological (black rot/club root resistance) characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from "Korso." Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms) analysis identified the presence of "G1/1" DNA segments (average 7.5%). Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1%) was higher than presence of novel bands (1.4%), and the presence of fragments specific to Brassica carinata (BBCC 2n = 34) were common (average 15.5%). Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4%) was more frequent than hypomethylation (4.8%). Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  13. Genetic and epigenetic alterations of Brassica nigra introgression lines from somatic hybridization: a resource for cauliflower improvement

    Directory of Open Access Journals (Sweden)

    Guixiang Wang

    2016-08-01

    Full Text Available Broad phenotypic variations were obtained previously in derivatives from the asymmetric somatic hybridization of cauliflower ‘Korso’ (Brassica oleracea var. botrytis, 2n = 18, CC genome and black mustard ‘G1/1’ (Brassica nigra, 2n = 16, BB genome. However, the mechanisms underlying these variations were unknown. In this study, 28 putative introgression lines (ILs were pre-selected according to a series of morphological (leaf shape and color, plant height and branching, curd features, and flower traits and physiological (black rot/club root resistance characters. Multi-color fluorescence in situ hybridization revealed that these plants contained 18 chromosomes derived from ‘Korso’. Molecular marker (65 simple sequence repeats and 77 amplified fragment length polymorphisms analysis identified the presence of ‘G1/1’ DNA segments (average 7.5%. Additionally, DNA profiling revealed many genetic and epigenetic differences among the ILs, including sequence alterations, deletions, and variation in patterns of cytosine methylation. The frequency of fragments lost (5.1% was significantly higher than presence of novel bands (1.4%, and the presence of fragments specific to B. carinata (BBCC 2n = 34 were common (average 15.5%. Methylation-sensitive amplified polymorphism analysis indicated that methylation changes were common and that hypermethylation (12.4% was more frequent than hypomethylation (4.8%. Our results suggested that asymmetric somatic hybridization and alien DNA introgression induced genetic and epigenetic alterations. Thus, these ILs represent an important, novel germplasm resource for cauliflower improvement that can be mined for diverse traits of interest to breeders and researchers.

  14. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

    Science.gov (United States)

    Nath, Aritro; Chan, Christina

    2016-01-04

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

  15. Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics.

    Science.gov (United States)

    Marchev, Andrey; Yordanova, Zhenya; Alipieva, Kalina; Zahmanov, Georgi; Rusinova-Videva, Snezhana; Kapchina-Toteva, Veneta; Simova, Svetlana; Popova, Milena; Georgiev, Milen I

    2016-09-01

    To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside.

  16. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

    International Nuclear Information System (INIS)

    Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

    2015-01-01

    Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O_2_−· and H_2O_2 being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ("1H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer

  17. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

    Energy Technology Data Exchange (ETDEWEB)

    Parlanti, Eleonora [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Sanchez, Massimo [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Fattibene, Paola [Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Falchi, Mario [National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, Eugenia, E-mail: dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy)

    2015-12-15

    Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O{sub 2−}· and H{sub 2}O{sub 2} being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ({sup 1}H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a

  18. Epilepsy in patients with GRIN2A alterations

    DEFF Research Database (Denmark)

    von Stülpnagel, Celina; Ensslen, M; Møller, R S

    2017-01-01

    indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic......OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were...... classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7...

  19. The genetic basis for altered blood vessel function in disease: large artery stiffening

    Directory of Open Access Journals (Sweden)

    Alex Agrotis

    2005-12-01

    Full Text Available Alex AgrotisThe Cell Biology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, AustraliaAbstract: The progressive stiffening of the large arteries in humans that occurs during aging constitutes a potential risk factor for increased cardiovascular morbidity and mortality, and is accompanied by an elevation in systolic blood pressure and pulse pressure. While the underlying basis for these changes remains to be fully elucidated, factors that are able to influence the structure and composition of the extracellular matrix and the way it interacts with arterial smooth muscle cells could profoundly affect the properties of the large arteries. Thus, while age and sex represent important factors contributing to large artery stiffening, the variation in growth-stimulating factors and those that modulate extracellular production and homeostasis are also being increasingly recognized to play a key role in the process. Therefore, elucidating the contribution that genetic variation makes to large artery stiffening could ultimately provide the basis for clinical strategies designed to regulate the process for therapeutic benefit.Keywords: arterial stiffness, genes, polymorphism, extracellular matrix proteins

  20. Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

    Directory of Open Access Journals (Sweden)

    Khanichi N. Charles

    2017-10-01

    Full Text Available Summary: Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice. : Deterioration of metabolic health is a hallmark of aging and generally thought to be detrimental to longevity. Charles et al. utilize FABP-deficient mice as a model to demonstrate that the preservation of metabolic health in this model persists throughout life, even under metabolic stress, but does not increase longevity. Keywords: fatty acid binding protein, aging, calorie restriction, metabolic health, inflammation, metaflammation, diabetes, obesity, de novo lipogenesis

  1. Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.

    Science.gov (United States)

    Van Roy, N; Van Limbergen, H; Vandesompele, J; Van Gele, M; Poppe, B; Salwen, H; Laureys, G; Manoel, N; De Paepe, A; Speleman, F

    2001-10-01

    Cancer cell lines are essential gene discovery tools and have often served as models in genetic and functional studies of particular tumor types. One of the future challenges is comparison and interpretation of gene expression data with the available knowledge on the genomic abnormalities in these cell lines. In this context, accurate description of these genomic abnormalities is required. Here, we show that a combination of M-FISH with banding analysis, standard FISH, and CGH allowed a detailed description of the genetic alterations in 16 neuroblastoma cell lines. In total, 14 cryptic chromosome rearrangements were detected, including a balanced t(2;4)(p24.3;q34.3) translocation in cell line NBL-S, with the 2p24 breakpoint located at about 40 kb from MYCN. The chromosomal origin of 22 marker chromosomes and 41 cytogenetically undefined translocated segments was determined. Chromosome arm 2 short arm translocations were observed in six cell lines (38%) with and five (31%) without MYCN amplification, leading to partial chromosome arm 2p gain in all but one cell line and loss of material in the various partner chromosomes, including 1p and 11q. These 2p gains were often masked in the GGH profiles due to MYCN amplification. The commonly overrepresented region was chromosome segment 2pter-2p22, which contains the MYCN gene, and five out of eleven 2p breakpoints clustered to the interface of chromosome bands 2p16 and 2p21. In neuroblastoma cell line SJNB-12, with double minutes (dmins) but no MYCN amplification, the dmins were shown to be derived from 16q22-q23 sequences. The ATBF1 gene, an AT-binding transcription factor involved in normal neurogenesis and located at 16q22.2, was shown to be present in the amplicon. This is the first report describing the possible implication of ATBF1 in neuroblastoma cells. We conclude that a combined approach of M-FISH, cytogenetics, and CGH allowed a more complete and accurate description of the genetic alterations occurring in the

  2. PIK3CA Mutation in Colorectal Cancer: Relationship with Genetic and Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    2008-06-01

    Full Text Available Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN. Microsatellite instability (MSI and CpG island methylator phenotype (CIMP are important molecular classifiers in colorectal cancer. However, the relationship between PIK3CA mutation, MSI and CIMP remains uncertain. Using Pyrosequencing technology, we detected PIK3CA mutations in 91 (15% of 590 population-based colorectal cancers. To determine CIMP status, we quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A (p16, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight. PIK3CA mutation was significantly associated with mucinous tumors [P = .0002; odds ratio (OR = 2.44], KRAS mutation (P < .0001; OR = 2.68, CIMP-high (P = .03; OR = 2.08, phospho–ribosomal protein S6 expression (P = .002; OR = 2.19, and FASN expression (P = .02; OR = 1.85 and inversely with p53 expression (P = .01; OR = 0.54 and β-catenin (CTNNB1 alteration (P = .004; OR = 0.43. In addition, PIK3CA G-to-A mutations were associated with MGMT loss (P = .001; OR = 3.24 but not with MGMT promoter methylation. In conclusion, PIK3CA mutation is significantly associated with other key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G>A mutation. In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level.

  3. Ontogeny of mouse vestibulo-ocular reflex following genetic or environmental alteration of gravity sensing.

    Directory of Open Access Journals (Sweden)

    Mathieu Beraneck

    Full Text Available The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied, gravity cannot be sensed and therefore maculo-ocular reflexes (MOR were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG and compared to non-centrifuged (control C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.

  4. Variation in MHC class II B genes in marbled murrelets: implications for delineating conservation units

    Science.gov (United States)

    C. Vásquez-Carrillo; V. Friesen; L. Hall; M.Z. Peery

    2013-01-01

    Conserving genetic variation is critical for maintaining the evolutionary potential and viability of a species. Genetic studies seeking to delineate conservation units, however, typically focus on characterizing neutral genetic variation and may not identify populations harboring local adaptations. Here, variation at two major histocompatibility complex (MHC) class II...

  5. Semi-automatic classification of skeletal morphology in genetically altered mice using flat-panel volume computed tomography.

    Directory of Open Access Journals (Sweden)

    Christian Dullin

    2007-07-01

    Full Text Available Rapid progress in exploring the human and mouse genome has resulted in the generation of a multitude of mouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT for high-resolution 3-D imaging and developed an algorithm with a computational intelligence system. First, we tested the accuracy and reliability of this approach by imaging discoidin domain receptor 2- (DDR2- deficient mice, which display distinct skull abnormalities as shown by comparative landmark-based analysis. High-contrast fpVCT data of the skull with 200 microm isotropic resolution and 8-s scan time allowed segmentation and computation of significant shape features as well as visualization of morphological differences. The application of a trained artificial neuronal network to these datasets permitted a semi-automatic and highly accurate phenotype classification of DDR2-deficient compared to C57BL/6 wild-type mice. Even heterozygous DDR2 mice with only subtle phenotypic alterations were correctly determined by fpVCT imaging and identified as a new class. In addition, we successfully applied the algorithm to classify knockout mice lacking the DDR1 gene with no apparent skull deformities. Thus, this new method seems to be a potential tool to identify novel mouse phenotypes with skull changes from transgenic and knockout mice on the basis of random mutagenesis as well as from genetic models. However for this purpose, new neuronal networks have to be created and trained. In summary, the combination of fpVCT images with artificial neuronal networks provides a reliable, novel method for rapid, cost-effective, and noninvasive primary screening tool to detect skeletal phenotypes in mice.

  6. Evaluation of genetic alteration induced by radon gas using the micronucleus test (Tradescantia sp. clone KU-20)

    International Nuclear Information System (INIS)

    Bruschi, Armando L.; Azevedo, Heliana de; Macacini, Jose F.; Roque, Claudio V.

    2011-01-01

    The first observations over the existence of radon gas (Rn), initially known as 'thorium emanation', were carried out between the end of 19 th and beginning of 20 th centuries. A result of uranium-238 (U 238 ) radioactive decay, radon is a tasteless, odorless and colorless gas under room temperature, with a 3.825-day half life and particle α emission in its decay, and as final product of its disintegration, the stable lead-206 isotope (Pb 206 ). Being it is the gas with the highest density known, closed and poor ventilated environments are favorable to its accumulation, with its inhalation being the highest health risk. The use of vegetal bioindicators has shown to be excellent on the monitoring of air quality and on mutagenic potential of various pollutants contained in the atmosphere. Within this context, the objective of this study was to evaluate the micronucleus test application potential utilizing the Tradescantia sp. clone KU-20, in order to evaluate genetic alterations induced by radon gas. Stems of Tradescantia sp. clone KU-20, previously immerse in Hoagland solution, were introduced in a radon detection equipment's calibration chamber (Alphaguard), containing radium salt. Afterwards, the accommodated stems were exposed to radon gas (the average radon concentration was 7.639 KBq/m3) for 24 hours. The results demonstrated an increase on micronucleus formation (39.23 + 2.143 MCN/100 tetrads) in stems exposed in relation to the negative control (18.00 + 1.396 MCN/100 tetrads). The difference between the values indicated a significant increase on micronucleus frequency in the inflorescences subjected to radon gas. The presented results demonstrated the micronucleus test application potential using Tradescantia clone KU-20 to evaluate genetic effects induced by radon gas. (author)

  7. Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jackline P. Ayres-Silva

    2018-02-01

    Full Text Available The genetic events associated with transformation of myeloproliferative neoplasms (MPNs to secondary acute myeloid leukemia (sAML, particularly in the subgroup of essential thrombocythemia (ET patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH and whole exome sequencing (WES to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47, and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu. All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation. Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.

  8. Genetically altering the expression of neutral trehalase gene affects conidiospore thermotolerance of the entomopathogenic fungus Metarhizium acridum

    Directory of Open Access Journals (Sweden)

    Peng Guoxiong

    2011-02-01

    Full Text Available Abstract Background The entomopathogenic fungus Metarhizium acridum has been used as an important biocontrol agent instead of insecticides for controlling crop pests throughout the world. However, its virulence varies with environmental factors, especially temperature. Neutral trehalase (Ntl hydrolyzes trehalose, which plays a role in environmental stress response in many organisms, including M. acridum. Demonstration of a relationship between Ntl and thermotolerance or virulence may offer a new strategy for enhancing conidiospore thermotolerance of entomopathogenic fungi through genetic engineering. Results We selected four Ntl over-expression and four Ntl RNA interference (RNAi transformations in which Ntl expression is different. Compared to the wild-type, Ntl mRNA expression was reduced to 35-66% in the RNAi mutants and increased by 2.5-3.5-fold in the over-expression mutants. The RNAi conidiospores exhibited less trehalase activity, accumulated more trehalose, and were much more tolerant of heat stress than the wild-type. The opposite effects were found in conidiospores of over-expression mutants compared to RNAi mutants. Furthermore, virulence was not altered in the two types of mutants compared to the wild type. Conclusions Ntl controlled trehalose accumulation in M. acridum by degrading trehalose, and thus affected conidiospore thermotolerance. These results offer a new strategy for enhancing conidiospore thermotolerance of entomopathogenic fungi without affecting virulence.

  9. Advancement of Phenotype Transformation of Cancer-associated Fibroblasts: 
from Genetic Alterations to Epigenetic Modification

    Directory of Open Access Journals (Sweden)

    Dali CHEN

    2015-02-01

    Full Text Available In the field of human cancer research, even though the vast majority attentions were paid to tumor cells as “the seeds”, the roles of tumor microenvironments as “the soil” are gradually explored in recent years. As a dominant compartment of tumor microenvironments, cancer-associated fibroblasts (CAFs were discovered to correlated with tumorigenesis, tumor progression and prognosis. And the exploration of the mechanisms of CAF phenotype transformation would conducive to the further understand of the CAFs function in human cancers. As we known that CAFs have four main origins, including epithelial cells, endothelial cells, mesenchymal stem cells (MSCs and local mesenchymal cells. However, researchers found that all these origins finally conduct similiar phenotypes from intrinsic to extrinsic ones. Thus, what and how a mechanism can conduct the phenotype transformation of CAFs with different origins? Two viewpoints are proposed to try to answer the quetsion, involving genetic alterations and epigenetic modifications. This review will systematically summarize the advancement of mechanisms of CAF phenotype transformations in the aspect of genentic and epigenetic modifications.

  10. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    Directory of Open Access Journals (Sweden)

    Wanchun Yang

    2014-01-01

    Full Text Available Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1 activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1 as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

  11. Genetic Romanticism

    DEFF Research Database (Denmark)

    Tupasela, Aaro

    2016-01-01

    inheritance as a way to unify populations within politically and geographically bounded areas. Thus, new genetics have contributed to the development of genetic romanticisms, whereby populations (human, plant, and animal) can be delineated and mobilized through scientific and medical practices to represent...

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

    Science.gov (United States)

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

    2016-02-01

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

  13. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

    Science.gov (United States)

    Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D'Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

    2015-12-01

    Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O₂₋• and H₂O₂ being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Aspen Delineation - Inyo National Forest [ds366

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of known aspen stands where aspen assessments were collected in the Inyo National Forest, Inyo County, California. The Inyo...

  15. Defining population structure and genetic signatures of decline in the giant garter snake (Thamnophis gigas): implications for conserving threatened species within highly altered landscapes

    Science.gov (United States)

    Wood, Dustin A.; Halstead, Brian J.; Casazza, Michael L.; Hansen, Eric C.; Wylie, Glenn D.; Vandergast, Amy

    2015-01-01

    Anthropogenic habitat fragmentation can disrupt the ability of species to disperse across landscapes, which can alter the levels and distribution of genetic diversity within populations and negatively impact long-term viability. The giant gartersnake (Thamnophis gigas) is a state and federally threatened species that historically occurred in the wetland habitats of California’s Great Central Valley. Despite the loss of 93 % of historic wetlands throughout the Central Valley, giant gartersnakes continue to persist in relatively small, isolated patches of highly modified agricultural wetlands. Gathering information regarding genetic diversity and effective population size represents an essential component for conservation management programs aimed at this species. Previous mitochondrial sequence studies have revealed historical patterns of differentiation, yet little is known about contemporary population structure and diversity. On the basis of 15 microsatellite loci, we estimate population structure and compare indices of genetic diversity among populations spanning seven drainage basins within the Central Valley. We sought to understand how habitat loss may have affected genetic differentiation, genetic diversity and effective population size, and what these patterns suggest in terms of management and restoration actions. We recovered five genetic clusters that were consistent with regional drainage basins, although three northern basins within the Sacramento Valley formed a single genetic cluster. Our results show that northern drainage basin populations have higher connectivity than among central and southern basins populations, and that greater differentiation exists among the more geographically isolated populations in the central and southern portion of the species’ range. Genetic diversity measures among basins were significantly different, and were generally lower in southern basin populations. Levels of inbreeding and evidence of population

  16. SLIC superpixels for object delineation UAV data

    NARCIS (Netherlands)

    Crommelinck, Sophie Charlotte; Bennett, R.M.; Gerke, Markus; Koeva, M.N.; Yang, M.Y.; Vosselman, G.; Stachniss, C.; Förstner, W.; Schneider, J.

    2017-01-01

    Unmanned aerial vehicles (UAV) are increasingly investigated with regard to their potential to create and update (cadastral) maps. UAVs provide a flexible and low-cost platform for high-resolution data, from which object outlines can be accurately delineated. This delineation could be automated with

  17. Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain.

    Science.gov (United States)

    Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

    2012-08-01

    Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.

  18. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    Science.gov (United States)

    Valera, Alexandra; López-Guillermo, Armando; Cardesa-Salzmann, Teresa; Climent, Fina; González-Barca, Eva; Mercadal, Santiago; Espinosa, Iñigo; Novelli, Silvana; Briones, Javier; Mate, José L; Salamero, Olga; Sancho, Juan M; Arenillas, Leonor; Serrano, Sergi; Erill, Nadina; Martínez, Daniel; Castillo, Paola; Rovira, Jordina; Martínez, Antonio; Campo, Elias; Colomo, Luis

    2013-10-01

    MYC alterations influence the survival of patients with diffuse large B-cell lymphoma. Most studies have focused on MYC translocations but there is little information regarding the impact of numerical alterations and protein expression. We analyzed the genetic alterations and protein expression of MYC, BCL2, BCL6, and MALT1 in 219 cases of diffuse large B-cell lymphoma. MYC rearrangement occurred as the sole abnormality (MYC single-hit) in 3% of cases, MYC and concurrent BCL2 and/or BCL6 rearrangements (MYC double/triple-hit) in 4%, MYC amplifications in 2% and MYC gains in 19%. MYC single-hit, MYC double/triple-hit and MYC amplifications, but not MYC gains or other gene rearrangements, were associated with unfavorable progression-free survival and overall survival. MYC protein expression, evaluated using computerized image analysis, captured the unfavorable prognosis of MYC translocations/amplifications and identified an additional subset of patients without gene alterations but with similar poor prognosis. Patients with tumors expressing both MYC/BCL2 had the worst prognosis, whereas those with double-negative tumors had the best outcome. High MYC expression was associated with shorter overall survival irrespectively of the International Prognostic Index and BCL2 expression. In conclusion, MYC protein expression identifies a subset of diffuse large B-cell lymphoma with very poor prognosis independently of gene alterations and other prognostic parameters.

  19. Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.

    Science.gov (United States)

    Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Main, Katharina M; Juul, Anders

    2016-04-01

    Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? FSHB and FSHR genetic variants exert, alone or their combination, distinct effects on reproductive hormone levels as well as ovarian follicle maturation in healthy peripubertal girls. FSHB and FSHR genetic variants impact reproductive hormone levels as well as associated pathologies in women. While FSHR c. 2039A>G is known to alter gonadotrophin levels in women, FSHR c.-29G>A has not yet been shown to exert effect and there are conflicting results concerning FSHB c.-211G>T. This population-based study included 633 girls recruited as part of two cohorts, the COPENHAGEN Puberty Study (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). Clinical examinations, including pubertal breast stage (Tanner's classification B1-B5) were performed. Circulating levels of FSH, luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH) and inhibin-B were assessed by immunoassays. In a subset of the girls (n = 91), ovarian volume and the number/size of antral follicles were assessed by TAUS. Genotypes were determined by competitive PCR. FSHR c.2039A>G minor alleles were positively associated with serum FSH (β = 0.08, P = 0.004), LH (β = 0.06, P = 0.012) and estradiol (β = 0.06, P = 0.017) (adjusted for Tanner stages). In a combined model, FSHR c.-29G>A and FSHR c.2039A>G alleles were positively associated with FSH levels in early-pubertal girls (B2 + B3, n = 327, r = 0.1, P = 0.02) and in young adolescents (B4 + B5, n = 149, r = 0.2, P = 0.01). Serum AMH and inhibin B levels were not significantly influenced by the single nucleotide polymorphisms (SNPs). Single SNPs were not associated with follicles

  20. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa).

    Science.gov (United States)

    Ziska, Lewis H; Gealy, David R; Tomecek, Martha B; Jackson, Aaron K; Black, Howard L

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2) between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2) from an early 20(th) century concentration (300 µmol mol(-1)) to current (400 µmol mol(-1)) and projected, mid-21(st) century (600 µmol mol(-1)) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1). The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2) also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2) could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  1. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa.

    Directory of Open Access Journals (Sweden)

    Lewis H Ziska

    Full Text Available Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO(2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO(2 from an early 20(th century concentration (300 µmol mol(-1 to current (400 µmol mol(-1 and projected, mid-21(st century (600 µmol mol(-1 values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol(-1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO(2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO(2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems.

  2. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    LENUS (Irish Health Repository)

    Nyhan, Michelle J

    2012-01-31

    BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  3. Interactive Cadastral Boundary Delineation from Uav Data

    Science.gov (United States)

    Crommelinck, S.; Höfle, B.; Koeva, M. N.; Yang, M. Y.; Vosselman, G.

    2018-05-01

    Unmanned aerial vehicles (UAV) are evolving as an alternative tool to acquire land tenure data. UAVs can capture geospatial data at high quality and resolution in a cost-effective, transparent and flexible manner, from which visible land parcel boundaries, i.e., cadastral boundaries are delineable. This delineation is to no extent automated, even though physical objects automatically retrievable through image analysis methods mark a large portion of cadastral boundaries. This study proposes (i) a methodology that automatically extracts and processes candidate cadastral boundary features from UAV data, and (ii) a procedure for a subsequent interactive delineation. Part (i) consists of two state-of-the-art computer vision methods, namely gPb contour detection and SLIC superpixels, as well as a classification part assigning costs to each outline according to local boundary knowledge. Part (ii) allows a user-guided delineation by calculating least-cost paths along previously extracted and weighted lines. The approach is tested on visible road outlines in two UAV datasets from Germany. Results show that all roads can be delineated comprehensively. Compared to manual delineation, the number of clicks per 100 m is reduced by up to 86 %, while obtaining a similar localization quality. The approach shows promising results to reduce the effort of manual delineation that is currently employed for indirect (cadastral) surveying.

  4. Rapid Genetic and Epigenetic Alterations under Intergeneric Genomic Shock in Newly Synthesized Chrysanthemum morifolium × Leucanthemum paludosum Hybrids (Asteraceae)

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5–50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses. PMID:24407856

  5. Rapid genetic and epigenetic alterations under intergeneric genomic shock in newly synthesized Chrysanthemum morifolium x Leucanthemum paludosum hybrids (Asteraceae).

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5-50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses.

  6. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression

    Directory of Open Access Journals (Sweden)

    Neha S. Raghavan

    2018-01-01

    Full Text Available Major depressive disorder (MDD is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY more immobile (WMI females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI. In adulthood, prepubertally ovariectomized (PrePubOVX animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal

  7. Anthropogenic fragmentation may not alter pre-existing patterns of genetic diversity and differentiation in perennial shrubs.

    Science.gov (United States)

    Llorens, Tanya M; Ayre, David J; Whelan, Robert J

    2018-04-01

    Many plant species have pollination and seed dispersal systems and evolutionary histories that have produced strong genetic structuring. These genetic patterns may be consistent with expectations following recent anthropogenic fragmentation, making it difficult to detect fragmentation effects if no prefragmentation genetic data are available. We used microsatellite markers to investigate whether severe habitat fragmentation may have affected the structure and diversity of populations of the endangered Australian bird-pollinated shrub Grevillea caleyi R.Br., by comparing current patterns of genetic structure and diversity with those of the closely related G. longifolia R.Br. that has a similar life history but has not experienced anthropogenic fragmentation. Grevillea caleyi and G. longifolia showed similar and substantial population subdivision at all spatial levels (global F' ST  = 0.615 and 0.454; S p  = 0.039 and 0.066), marked isolation by distance and large heterozygous deficiencies. These characteristics suggest long-term effects of inbreeding in self-compatible species that have poor seed dispersal, limited connectivity via pollen flow and undergo population bottlenecks because of periodic fires. Highly structured allele size distributions, most notably in G. caleyi, imply historical processes of drift and mutation were important in isolated subpopulations. Genetic diversity did not vary with population size but was lower in more isolated populations for both species. Through this comparison, we reject the hypothesis that anthropogenic fragmentation has impacted substantially on the genetic composition or structure of G. caleyi populations. Our results suggest that highly self-compatible species with limited dispersal may be relatively resilient to the genetic changes predicted to follow habitat fragmentation. © 2018 John Wiley & Sons Ltd.

  8. The Protective Effect of Minocycline in a Paraquat-Induced Parkinson's Disease Model in Drosophila is Modified in Altered Genetic Backgrounds

    Directory of Open Access Journals (Sweden)

    Arati A. Inamdar

    2012-01-01

    Full Text Available Epidemiological studies link the herbicide paraquat to increased incidence of Parkinson's disease (PD. We previously reported that Drosophila exposed to paraquat recapitulate PD symptoms, including region-specific degeneration of dopaminergic neurons. Minocycline, a tetracycline derivative, exerts ameliorative effects in neurodegenerative disease models, including Drosophila. We investigated whether our environmental toxin-based PD model could contribute to an understanding of cellular and genetic mechanisms of minocycline action and whether we could assess potential interference with these drug effects in altered genetic backgrounds. Cofeeding of minocycline with paraquat prolonged survival, rescued mobility defects, blocked generation of reactive oxygen species, and extended dopaminergic neuron survival, as has been reported previously for a genetic model of PD in Drosophila. We then extended this study to identify potential interactions of minocycline with genes regulating dopamine homeostasis that might modify protection against paraquat and found that deficits in GTP cyclohydrolase adversely affect minocycline rescue. We further performed genetic studies to identify signaling pathways that are necessary for minocycline protection against paraquat toxicity and found that mutations in the Drosophila genes that encode c-Jun N-terminal kinase (JNK and Akt/Protein kinase B block minocycline rescue.

  9. Aspen Delineation - Sierra State Parks [ds380

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of aspen stands associated with stand assessment data (SIERRA_SP_PTS) collected in aspen stands on lands administered by the...

  10. Aspen Delineation - Lassen National Forest [ds372

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of aspen stands associated with stand assessment data (LASSEN_NF_EAGLELAKE_PTS) collected in aspen stands in the in the Eagle...

  11. Delineating organs at risk in radiation therapy

    CERN Document Server

    Ausili Cèfaro, Giampiero; Perez, Carlos A

    2014-01-01

    This book offers an invaluable guide to the delineation of organs at risk of toxicity in patients undergoing radiotherapy. It details the radiological anatomy of organs at risk as seen on typical radiotherapy planning CT scans.

  12. Aspen Delineation - Sequoia National Forest [ds378

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of aspen stands associated with stand assessment data (SEQUOIA_NF_PTS) collected in aspen stands in the Cannell Meadows Ranger...

  13. FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain.

    Directory of Open Access Journals (Sweden)

    Thais S Rizzi

    Full Text Available Multiple lines of evidence suggest that fatty acids (FA play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF and FA desaturase (FADS genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193 and mice (93 and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03. Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition.

  14. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, Ingelise Bjerring; Worm, Jesper; Ralfkiaer, Elisabeth

    2007-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, we...

  15. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  16. Alteration of sexual reproduction and genetic diversity in the kelp species Laminaria digitata at the southern limit of its range.

    Directory of Open Access Journals (Sweden)

    Luz Valeria Oppliger

    Full Text Available Adaptation to marginal habitats at species range-limits has often been associated with parthenogenetic reproduction in terrestrial animals and plants. Laboratory observations have shown that brown algae exhibit a high propensity for parthenogenesis by various mechanisms. The kelp Laminaria digitata is an important component of the ecosystem in Northern European rocky intertidal habitats. We studied four L. digitata populations for the effects of marginality on genetic diversity and sexual reproduction. Two populations were marginal: One (Locquirec, in Northern Brittany was well within the geographic range, but was genetically isolated from other populations by large stretches of sandy beaches. Another population was at the range limits of the species (Quiberon, in Southern Brittany and was exposed to much higher seasonal temperature changes. Microsatellite analyses confirmed that these populations showed decreased genetic and allelic diversity, consistent with marginality and genetic isolation. Sporophytes from both marginal populations showed greatly diminished spore-production compared to central populations, but only the southern-limit population (Quiberon showed a high propensity for producing unreduced (2N spores. Unreduced 2N spores formed phenotypically normal gametophytes with nuclear area consistent with ≥2N DNA contents, and microsatellite studies suggested these were produced at least in part by automixis. However, despite this being the dominant path of spore production in Quiberon sporophyte individuals, the genetic evidence indicated the population was maintained mostly by sexual reproduction. Thus, although spore production and development showed the expected tendency of geographical parthenogenesis in marginal populations, this appeared to be a consequence of maladaptation, rather than an adaptation to, life in a marginal habitat.

  17. Alterations in the α2 δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies.

    Science.gov (United States)

    Santolini, Ines; Celli, Roberta; Cannella, Milena; Imbriglio, Tiziana; Guiducci, Michela; Parisi, Pasquale; Schubert, Julian; Iacomino, Michele; Zara, Federico; Lerche, Holger; Moyanova, Slavianka; Ngomba, Richard Teke; van Luijtelaar, Gilles; Battaglia, Giuseppe; Bruno, Valeria; Striano, Pasquale; Nicoletti, Ferdinando

    2017-11-01

    Thrombospondins, which are known to interact with the α 2 δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). We measured the transcripts of thrombospondin-1 and α 2 δ subunit, and protein levels of α 2 δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  18. Touch imprint cytology with massively parallel sequencing (TIC-seq): a simple and rapid method to snapshot genetic alterations in tumors.

    Science.gov (United States)

    Amemiya, Kenji; Hirotsu, Yosuke; Goto, Taichiro; Nakagomi, Hiroshi; Mochizuki, Hitoshi; Oyama, Toshio; Omata, Masao

    2016-12-01

    Identifying genetic alterations in tumors is critical for molecular targeting of therapy. In the clinical setting, formalin-fixed paraffin-embedded (FFPE) tissue is usually employed for genetic analysis. However, DNA extracted from FFPE tissue is often not suitable for analysis because of its low levels and poor quality. Additionally, FFPE sample preparation is time-consuming. To provide early treatment for cancer patients, a more rapid and robust method is required for precision medicine. We present a simple method for genetic analysis, called touch imprint cytology combined with massively paralleled sequencing (touch imprint cytology [TIC]-seq), to detect somatic mutations in tumors. We prepared FFPE tissues and TIC specimens from tumors in nine lung cancer patients and one patient with breast cancer. We found that the quality and quantity of TIC DNA was higher than that of FFPE DNA, which requires microdissection to enrich DNA from target tissues. Targeted sequencing using a next-generation sequencer obtained sufficient sequence data using TIC DNA. Most (92%) somatic mutations in lung primary tumors were found to be consistent between TIC and FFPE DNA. We also applied TIC DNA to primary and metastatic tumor tissues to analyze tumor heterogeneity in a breast cancer patient, and showed that common and distinct mutations among primary and metastatic sites could be classified into two distinct histological subtypes. TIC-seq is an alternative and feasible method to analyze genomic alterations in tumors by simply touching the cut surface of specimens to slides. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Forest Delineation Based on Airborne LIDAR Data

    Directory of Open Access Journals (Sweden)

    Norbert Pfeifer

    2012-03-01

    Full Text Available The delineation of forested areas is a critical task, because the resulting maps are a fundamental input for a broad field of applications and users. Different national and international forest definitions are available for manual or automatic delineation, but unfortunately most definitions lack precise geometrical descriptions for the different criteria. A mandatory criterion in forest definitions is the criterion of crown coverage (CC, which defines the proportion of the forest floor covered by the vertical projection of the tree crowns. For loosely stocked areas, this criterion is especially critical, because the size and shape of the reference area for calculating CC is not clearly defined in most definitions. Thus current forest delineations differ and tend to be non-comparable because of different settings for checking the criterion of CC in the delineation process. This paper evaluates a new approach for the automatic delineation of forested areas, based on airborne laser scanning (ALS data with a clearly defined method for calculating CC. The new approach, the ‘tree triples’ method, is based on defining CC as a relation between the sum of the crown areas of three neighboring trees and the area of their convex hull. The approach is applied and analyzed for two study areas in Tyrol, Austria. The selected areas show a loosely stocked forest at the upper timberline and a fragmented forest on the hillside. The fully automatic method presented for delineating forested areas from ALS data shows promising results with an overall accuracy of 96%, and provides a beneficial tool for operational applications.

  20. Characterization of a cultured human T-cell line with genetically altered ribonucleotide reductase activity. Model for immunodeficiency.

    Science.gov (United States)

    Waddell, D; Ullman, B

    1983-04-10

    From human CCRF-CEM T-cells growing in continuous culture, we have selected, isolated, and characterized a clonal cell line, APHID-D2, with altered ribonucleotide reductase activity. In comparative growth rate experiments, the APHID-D2 cell line is less sensitive than the parental cell line to growth inhibition by deoxyadenosine in the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. The APHID-D2 cell line has elevated levels of all four dNTPs. The resistance of the APHID-D2 cell line to growth inhibition by deoxyadenosine and the abnormal dNTP levels can be explained by the fact that the APHID-D2 ribonucleotide reductase, unlike the parental ribonucleotide reductase, is not normally sensitive to inhibition by dATP. These results suggest that the allosteric site of ribonucleotide reductase which binds both dATP and ATP is altered in the APHID-D2 line. The isolation of a mutant clone of human T-cells which contains a ribonucleotide reductase that has lost its normal sensitivity to dATP and which is resistant to deoxyadenosine-mediated growth inhibition suggests that a primary pathogenic target of accumulated dATP in lymphocytes from patients with adenosine deaminase deficiency may be the cellular ribonucleotide reductase.

  1. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Directory of Open Access Journals (Sweden)

    Nengyi Zhang

    2010-04-01

    Full Text Available Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system.We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication.Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  2. Temporal and seasonal changes of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine and quinine in Guinea-Bissau between 2003 and 2012

    DEFF Research Database (Denmark)

    Jovel, Irina Tatiana; Kofoed, Poul-Erik; Rombo, Lars

    2015-01-01

    BACKGROUND: Guinea-Bissau, West-Africa introduced artemether-lumefantrine in 2008 but quinine has also been commonly prescribed for treatment of uncomplicated Plasmodium falciparum malaria. An efficacious high-dose chloroquine treatment regimen was used previously. Temporal and seasonal changes...... of genetic polymorphisms associated with altered drug susceptibility to chloroquine, lumefantrine and quinine are described. METHODS: Pfcrt K76T, pfmdr1 gene copy numbers, N86Y, Y184F and 1034-1246 sequences were determined using PCR-based methods. Blood samples came from virtually all (n=1806) children aged.......001). CONCLUSIONS: Following the discontinuation of an effective chloroquine regimen highly artemether-lumefantrine susceptible P. falciparum (with pfcrt 76T) accumulated possibly due to suboptimal use of quinine and despite a fitness cost linked to 76T....

  3. Targeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium).

    Science.gov (United States)

    Lim, Sun Min; Kim, Hye Ryun; Cho, Eun Kyung; Min, Young Joo; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil; Cho, Byoung Chul; Lee, Ji-Hyun; Jeong, Hye Cheol; Kim, Eun Kyung; Kim, Joo-Hang

    2016-06-14

    Non-small-cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations may exhibit primary resistance to EGFR tyrosine kinase inhibitor (TKI). We aimed to examine genomic alterations associated with de novo resistance to gefitinib in a prospective study of NSCLC patients. One-hundred and fifty two patients with activating EGFR mutations were included in this study and 136 patients' tumor sample were available for targeted sequencing of genomic alterations in 22 genes using the Colon and Lung Cancer panel (Ampliseq, Life Technologies). All 132 patients with EGFR mutation were treated with gefitinib for their treatment of advanced NSCLC. Twenty patients showed primary resistance to EGFR TKI, and were classified as non-responders. A total of 543 somatic single-nucleotide variants (498 missense, 13 nonsense) and 32 frameshift insertions/deletions, with a median of 3 mutations per sample. TP53 was most commonly mutated (47%) and mutations in SMAD4 was also common (19%), as well as DDR2 (16%), PIK3CA (15%), STK11 (14%), and BRAF (7%). Genomic mutations in the PI3K/Akt/mTOR pathway were commonly found in non-responders (45%) compared to responders (27%), and they had significantly shorter progression-free survival and overall survival compared to patients without mutations (2.1 vs. 12.8 months, P=0.04, 15.7 vs. not reached, PAkt/mTOR pathway were commonly identified in non-responders and may confer resistance to EGFR TKI. Screening lung adenocarcinoma patients with clinical cancer gene test may aid in selecting out those who show primary resistance to EGFR TKI (NCT01697163).

  4. Genetic deletion of the P2Y2 receptor offers significant resistance to development of lithium-induced polyuria accompanied by alterations in PGE2 signaling.

    Science.gov (United States)

    Zhang, Yue; Pop, Ioana L; Carlson, Noel G; Kishore, Bellamkonda K

    2012-01-01

    Lithium (Li)-induced polyuria is due to resistance of the medullary collecting duct (mCD) to the action of arginine vasopressin (AVP), apparently mediated by increased production of PGE(2). We previously reported that the P2Y(2) receptor (P2Y(2)-R) antagonizes the action of AVP on the mCD and may play a role in Li-induced polyuria by enhancing the production of PGE(2) in mCD. Hence, we hypothesized that genetic deletion of P2Y(2)-R should ameliorate Li-induced polyuria. Wild-type (WT) or P2Y(2)-R knockout (KO) mice were fed normal or Li-added diets for 14 days and euthanized. Li-induced polyuria, and decreases in urine osmolality and AQP2 protein abundance in the renal medulla, were significantly less compared with WT mice despite the lack of differences in Li intake or terminal serum or inner medullary tissue Li levels. Li-induced increased urinary excretion of PGE(2) was not affected in KO mice. However, prostanoid EP(3) receptor (EP3-R) protein abundance in the renal medulla of KO mice was markedly lower vs. WT mice, irrespective of the dietary regimen. The protein abundances of other EP-Rs were not altered across the groups irrespective of the dietary regimen. Ex vivo stimulation of mCD with PGE(2) generated significantly more cAMP in Li-fed KO mice (130%) vs. Li-fed WT mice (100%). Taken together, these data suggest 1) genetic deletion of P2Y(2)-R offers significant resistance to the development of Li-induced polyuria; and 2) this resistance is apparently due to altered PGE(2) signaling mediated by a marked decrease in EP3-R protein abundance in the medulla, thus attenuating the EP3-mediated decrease in cAMP levels in mCD.

  5. Delineating Concept Meanings: The Case of Terrorism.

    Science.gov (United States)

    Kleg, Milton; Mahlios, Marc

    1990-01-01

    Presents a teacher-initiated model for reaching class consensus on the meaning of confusing or interchangeable concepts in social studies classrooms. Illustrates the model by delineating terrorism. Shows procedural steps that involve students in self and small group interviews where definitions are clarified until consensus is reached. Suggests…

  6. Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells

    International Nuclear Information System (INIS)

    Denner, Joachim; Specke, Volker; Thiesen, Ulla; Karlas, Alexander; Kurth, Reinhard

    2003-01-01

    Human-tropic porcine endogenous retroviruses (PERV) such as PERV-A and PERV-B can infect human cells and are therefore a potential risk to recipients of xenotransplants. A similar risk is posed by recombinant viruses containing the receptor-binding site of PERV-A and large parts of the genome of the ecotropic PERV-C including its long terminal repeat (LTR). We describe here the unique organization of the PERV-C LTR and its changes during serial passage of recombinant virus in human cells. An increase in virus titer correlated with an increase in LTR length, caused by multiplication of 37-bp repeats containing nuclear factor Y binding sites. Luciferase dual reporter assays revealed a correlation between the number of repeats and the extent of expression. No alterations have been observed in the receptor-binding site, indicating that the increased titer is due to the changes in the LTR. These data indicate that recombinant PERVs generated during infection of human cells can adapt and subsequently replicate with greater efficiency

  7. Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels.

    Science.gov (United States)

    Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B; Parikh, Alexander; Revetta, Frank; Washington, M Kay; Vnencak-Jones, Cindy; Shi, Chanjuan

    2014-05-01

    Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (PSMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma.

  8. Clinical characterization of a novel calcium sensing receptor genetic alteration in a Greek patient with autosomal dominant hypocalcemia type 1.

    Science.gov (United States)

    Papadopoulou, Anna; Gole, Evangelia; Melachroinou, Katerina; Trangas, Theoni; Bountouvi, Evaggelia; Papadimitriou, Anastasios

    2017-04-01

    Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor (CaSR) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH. The functional impact of the novel mutation identified was assessed in cultured HEK 293T cells, transfected with either the wild type (WT) or mutant CaSR, by evaluating intracellular calcium ([Ca2+]i) influx after stimulation with extracellular calcium (Ca2+). Several BMD measurements were performed during the patient's follow-up until late puberty. A novel CaSR mutation (p.L123S) was identified, which, as demonstrated by functional analysis, renders CaSR more sensitive to extracellular changes of Ca2+ compared with the WT, although the difference is not statistically significant. BMD measurements, from early childhood to late puberty, revealed high normal to elevated BMD. We present the first Greek patient, to our knowledge, with sporadic ADH due to a novel gain-of-function mutation of the CaSR gene.

  9. Evaluation of the genetic alterations in direct and indirect exposures of hexavalent chromium [Cr(VI)] in leather tanning industry workers North Arcot District, South India.

    Science.gov (United States)

    Balachandar, Vellingiri; Arun, Meyyazhagan; Mohana Devi, Subramaniam; Velmurugan, Palanivel; Manikantan, Pappusamy; Karthick Kumar, Alagamuthu; Sasikala, Keshavarao; Venkatesan, Chinnakulandai

    2010-10-01

    The focal aim of the present study was to identify the genetic alterations occurring in the tannery workers and surrounding inhabitants chronically exposed to hexavalent chromium [Cr(VI)]. A total of 108 samples which includes 72 exposed subjects [36 directly exposed (DE) subjects and 36 indirectly exposed (IE) subjects] and 36 controls were recruited for this study. The exposed subjects and controls were selected based on the Cr level present in air and their urine. Directly exposed subjects were categorized based on their work duration in the tannery industries, whereas the indirectly exposed subjects were categorized based on their year of residence in the place adjacent to tannery industries for more than 3 decades. Controls were normal and healthy. Age was matched for the exposed subjects and controls. The exposed subjects as well as the controls were categorized based on their age (group I, 41 years). Cell cultures were established from blood samples (5 ml from each subject) collected from the subjects (exposed subjects and controls) after obtaining informed consent. G-banding (Giemsa staining) of the cultures, micronucleus (MN) assay and comet assay were used to identify the genetic alterations of individuals exposed to Cr(VI) in comparison with the controls. A higher degree of total CA [12 ± 8.49 (21-25 years)] and MN [18.69 ± 7.39 (11-15 years)] was found in DE subjects compared to other groups. In IE subjects, elevated levels of CA [5.67 ± 1.15 (51-60 years)] and MN [25 ± 9.89 (71-80 years)] were observed. As expected, controls exhibited minimal number of alterations. The overall CA frequency due to Cr exposure was significantly different from that of the controls for both chromatid and chromosome type aberrations (P < 0.05 by ANOVA). The MN/1,000 binucleated cells were significantly increased (P < 0.05) in the peripheral lymphocytes of DE and IE subjects in comparison with controls. The mean tail length of comet assay for DE, IE and controls were

  10. Genetic alteration with variable intron/exon organization amongst five PI-homoeologous genes in Platanus acerifolia.

    Science.gov (United States)

    Zhang, Jiaqi; Guo, Cong; Liu, Guofeng; Li, Zhineng; Li, Xiaomei; Bao, Manzhu

    2011-03-01

    Flower development has been extensively characterized in the model species Arabidopsis thaliana and Antirrhinum majus. However, there have been few studies in woody species. Here, we report the isolation and characterization of five PISTILLATA (PI) homoeologous genes (PaPI1-to-5) from the London Plane tree (Platanus acerifolia Willd). PaPI1 and PaPI2 show a similar genomic structure to other known PI homoeologs, but PaPI3/4/5 lack intron sequences. In addition, PaPI5 lacks the third, fourth and fifth exons which encode the K-domain. These altered gene copies may have originated as 'processed' retrogenes. PaPI2 appears micro-regulated by alternative splicing, displaying three splice forms (PaPI2a, PaPI2b and PaPI2c). RT-PCR analysis showed different expression profiles and transcript abundance for the five PaPI genes. PaPI transcripts encoding full-length polypeptides were expressed predominantly in male/female inflorescences and PaPI2a was the most abundant transcript (59%) indicating that PaPI2 may be the major functional PI-homoeolog in London Plane. Phenotypic characterization in a heterologous expression system demonstrated that the full-length PaPI product functions as a B class gene. By contrast the PaPI5 form, which lacks the K-domain, had no apparent effect on flower development. In vitro studies also demonstrated that the K-domain is required to form PaPI/PaAP3 heterodimers. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Delineation, characterization, and classification of topographic eminences

    Science.gov (United States)

    Sinha, Gaurav

    Topographic eminences are defined as upwardly rising, convex shaped topographic landforms that are noticeably distinct in their immediate surroundings. As opposed to everyday objects, the properties of a topographic eminence are dependent not only on how it is conceptualized, but is also intrinsically related to its spatial extent and its relative location in the landscape. In this thesis, a system for automated detection, delineation and characterization of topographic eminences based on an analysis of digital elevation models is proposed. Research has shown that conceptualization of eminences (and other landforms) is linked to the cultural and linguistic backgrounds of people. However, the perception of stimuli from our physical environment is not subject to cultural or linguistic bias. Hence, perceptually salient morphological and spatial properties of the natural landscape can form the basis for generically applicable detection and delineation of topographic eminences. Six principles of cognitive eminence modeling are introduced to develop the philosophical foundation of this research regarding eminence delineation and characterization. The first step in delineating eminences is to automatically detect their presence within digital elevation models. This is achieved by the use of quantitative geomorphometric parameters (e.g., elevation, slope and curvature) and qualitative geomorphometric features (e.g., peaks, passes, pits, ridgelines, and valley lines). The process of eminence delineation follows that of eminence detection. It is posited that eminences may be perceived either as monolithic terrain objects, or as composites of morphological parts (e.g., top, bottom, slope). Individual eminences may also simultaneously be conceived as comprising larger, higher order eminence complexes (e.g., mountain ranges). Multiple algorithms are presented for the delineation of simple and complex eminences, and the morphological parts of eminences. The proposed eminence

  12. Recent advances in probabilistic species pool delineations

    Directory of Open Access Journals (Sweden)

    Dirk Nikolaus Karger

    2016-07-01

    Full Text Available A species pool is the set of species that could potentially colonize and establish within a community. It has been a commonly used concept in biogeography since the early days of MacArthur and Wilson’s work on Island Biogeography. Despite their simple and appealing definition, an operational application of species pools is bundled with a multitude of problems, which have often resulted in arbitrary decisions and workarounds when defining species pools. Two recently published papers address the operational problems of species pool delineations, and show ways of delineating them in a probabilistic fashion. In both papers, species pools were delineated using a process-based, mechanistical approach, which opens the door for a multitude of new applications in biogeography. Such applications include detecting the hidden signature of biotic interactions, disentangling the geographical structure of community assembly processes, and incorporating a temporal extent into species pools. Although similar in their conclusions, both ‘probabilistic approaches’ differ in their implementation and definitions. Here I give a brief overview of the differences and similarities of both approaches, and identify the challenges and advantages in their application.

  13. Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

    Science.gov (United States)

    Conti, Salvatore; Gallo, Enzo; Sioletic, Stefano; Facciolo, Francesco; Palmieri, Giovannella; Lauriola, Libero; Evoli, Amelia; Martucci, Robert; Di Benedetto, Anna; Novelli, Flavia; Giannarelli, Diana; Deriu, Gloria; Granone, Pierluigi; Ottaviano, Margaret; Muti, Paola; Pescarmona, Edoardo; Marino, Mirella

    2016-03-01

    The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.

  14. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

    Science.gov (United States)

    Whitcomb, David C.; LaRusch, Jessica; Krasinskas, Alyssa M.; Klei, Lambertus; Smith, Jill P.; Brand, Randall E.; Neoptolemos, John P.; Lerch, Markus M.; Tector, Matt; Sandhu, Bimaljit S.; Guda, Nalini M.; Orlichenko, Lidiya; Alkaade, Samer; Amann, Stephen T.; Anderson, Michelle A.; Baillie, John; Banks, Peter A.; Conwell, Darwin; Coté, Gregory A.; Cotton, Peter B.; DiSario, James; Farrer, Lindsay A.; Forsmark, Chris E.; Johnstone, Marianne; Gardner, Timothy B.; Gelrud, Andres; Greenhalf, William; Haines, Jonathan L.; Hartman, Douglas J.; Hawes, Robert A.; Lawrence, Christopher; Lewis, Michele; Mayerle, Julia; Mayeux, Richard; Melhem, Nadine M.; Money, Mary E.; Muniraj, Thiruvengadam; Papachristou, Georgios I.; Pericak-Vance, Margaret A.; Romagnuolo, Joseph; Schellenberg, Gerard D.; Sherman, Stuart; Simon, Peter; Singh, Vijay K.; Slivka, Adam; Stolz, Donna; Sutton, Robert; Weiss, Frank Ulrich; Wilcox, C. Mel; Zarnescu, Narcis Octavian; Wisniewski, Stephen R.; O'Connell, Michael R.; Kienholz, Michelle L.; Roeder, Kathryn; Barmada, M. Michael; Yadav, Dhiraj; Devlin, Bernie; Albert, Marilyn S.; Albin, Roger L.; Apostolova, Liana G.; Arnold, Steven E.; Baldwin, Clinton T.; Barber, Robert; Barnes, Lisa L.; Beach, Thomas G.; Beecham, Gary W.; Beekly, Duane; Bennett, David A.; Bigio, Eileen H.; Bird, Thomas D.; Blacker, Deborah; Boxer, Adam; Burke, James R.; Buxbaum, Joseph D.; Cairns, Nigel J.; Cantwell, Laura B.; Cao, Chuanhai; Carney, Regina M.; Carroll, Steven L.; Chui, Helena C.; Clark, David G.; Cribbs, David H.; Crocco, Elizabeth A.; Cruchaga, Carlos; DeCarli, Charles; Demirci, F. Yesim; Dick, Malcolm; Dickson, Dennis W.; Duara, Ranjan; Ertekin-Taner, Nilufer; Faber, Kelley M.; Fallon, Kenneth B.; Farlow, Martin R.; Ferris, Steven; Foroud, Tatiana M.; Frosch, Matthew P.; Galasko, Douglas R.; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H.; Ghetti, Bernardino; Gilbert, John R.; Gilman, Sid; Glass, Jonathan D.; Goate, Alison M.; Graff-Radford, Neill R.; Green, Robert C.; Growdon, John H.; Hakonarson, Hakon; Hamilton-Nelson, Kara L.; Hamilton, Ronald L.; Harrell, Lindy E.; Head, Elizabeth; Honig, Lawrence S.; Hulette, Christine M.; Hyman, Bradley T.; Jicha, Gregory A.; Jin, Lee-Way; Jun, Gyungah; Kamboh, M. Ilyas; Karydas, Anna; Kaye, Jeffrey A.; Kim, Ronald; Koo, Edward H.; Kowall, Neil W.; Kramer, Joel H.; Kramer, Patricia; Kukull, Walter A.; LaFerla, Frank M.; Lah, James J.; Leverenz, James B.; Levey, Allan I.; Li, Ge; Lin, Chiao-Feng; Lieberman, Andrew P.; Lopez, Oscar L.; Lunetta, Kathryn L.; Lyketsos, Constantine G.; Mack, Wendy J.; Marson, Daniel C.; Martin, Eden R.; Martiniuk, Frank; Mash, Deborah C.; Masliah, Eliezer; McKee, Ann C.; Mesulam, Marsel; Miller, Bruce L.; Miller, Carol A.; Miller, Joshua W.; Montine, Thomas J.; Morris, John C.; Murrell, Jill R.; Naj, Adam C.; Olichney, John M.; Parisi, Joseph E.; Peskind, Elaine; Petersen, Ronald C.; Pierce, Aimee; Poon, Wayne W.; Potter, Huntington; Quinn, Joseph F.; Raj, Ashok; Raskind, Murray; Reiman, Eric M.; Reisberg, Barry; Reitz, Christiane; Ringman, John M.; Roberson, Erik D.; Rosen, Howard J.; Rosenberg, Roger N.; Sano, Mary; Saykin, Andrew J.; Schneider, Julie A.; Schneider, Lon S.; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Tsuang, Debby W.; Valladares, Otto; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vardarajan, Badri N.; Vinters, Harry V.; Vonsattel, Jean Paul; Wang, Li-San; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Williamson, Jennifer; Woltjer, Randall L.; Wright, Clinton B.; Younkin, Steven G.; Yu, Chang-En; Yu, Lei

    2012-01-01

    Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07. PMID:23143602

  15. Comparação dos algoritmos delineação rápida em cadeia e seriação, para a construção de mapas genéticos Comparison of algorithms rapid chain delineation and seriation, for the construction of genetic linkage maps

    Directory of Open Access Journals (Sweden)

    Marcelo Mollinari

    2008-04-01

    Full Text Available O objetivo deste trabalho foi avaliar a eficiência, na construção de mapas genéticos, dos algoritmos seriação e delineação rápida em cadeia, além dos critérios para avaliação de ordens: produto mínimo das frações de recombinação adjacentes, soma mínima das frações de recombinação adjacentes e soma máxima dos LOD Scores adjacentes, quando usados com o algoritmo de verificação de erros " ripple" . Foi simulado um mapa com 24 marcadores, posicionados aleatoriamente a distâncias variadas, com média 10 cM. Por meio do método Monte Carlo, foram obtidas 1.000 populações de retrocruzamento e 1.000 populações F2, com 200 indivíduos cada, e diferentes combinações de marcadores dominantes e co-dominantes (100% co-dominantes, 100% dominantes e mistura com 50% co-dominantes e 50% dominantes. Foi, também, simulada a perda de 25, 50 e 75% dos dados. Observou-se que os dois algoritmos avaliados tiveram desempenho semelhante e foram sensíveis à presença de dados perdidos e à presença de marcadores dominantes; esta última dificultou a obtenção de estimativas com boa acurácia, tanto da ordem quanto da distância. Além disso, observou-se que o algoritmo " ripple" geralmente aumenta o número de ordens corretas e pode ser combinado com os critérios soma mínima das frações de recombinação adjacentes e produto mínimo das frações de recombinação adjacentes.The objective of this work was to evaluate the efficiency for the construction of genetic linkage maps of the algorithms seriation and rapid chain delineation, as well as the criteria: product of adjacent recombination fractions, sum of adjacent recombination fractions, and sum of adjacent LOD Scores, used with the ripple algorithm. A genetic linkage map was simulated containing 24 markers with random distances between them, with an average of 10 cM. Using the Monte Carlo method, 1,000 backcross populations and 1,000 F2 populations were simulated. The

  16. Toriello-Carey syndrome : Delineation and review

    NARCIS (Netherlands)

    Toriello, HV; Carey, JC; Addor, MC; Allen, W; Burke, L; Chun, N; Dobyns, W; Elias, E; Gallagher, R; Hordijk, R; Hoyme, G; Irons, M; Jewett, T; LeMerrer, M; Lubinsky, M; Martin, R; McDonald-McGinn, D; Neumann, L; Newman, W; Pauli, R; Seaver, L; Tsai, A; Wargowsky, D; Williams, M; Zackai, E

    2003-01-01

    Toriello and Carey [1988: Am J Med Genet 31:17-23] first described a syndrome with component manifestations of corpus callosum agenesis, unusual facial appearance, Robin sequence, and other anomalies. This was termed the Toriello-Carey syndrome by Lacombe et al. [1992: Am J Med Genet 42:374-376].

  17. A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.

    Science.gov (United States)

    Geng, Yanyan; Ferreira, Juan J; Dzikunu, Victor; Butler, Alice; Lybaert, Pascale; Yuan, Peng; Magleby, Karl L; Salkoff, Lawrence; Santi, Celia M

    2017-05-26

    To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K + ) channels and resultant K + efflux. Sperm-specific SLO3 K + channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K + conductance is both Ca 2+ - and pH i -sensitive. It has been debated whether Ca 2+ -sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca 2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca 2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca 2+ , the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca 2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. The study of target delineation and target movement of whole breast assisted by active breathing control in intensity modulated radiotherapy after breast conservative surgery

    International Nuclear Information System (INIS)

    Li Jianbing; Yu Jinming; Ma Zhifang; Lu Jie; Sun Tao; Guo Shoufang; Wang Jingguo

    2009-01-01

    Objective: To explore the influence of different delineators and different delineating time on target determination of the whole breast and to explore intrafraction and interfraction target displacements of the breast on moderate deep inspiration breathing hold (mDIBH) assisted by active breathing control (ABC) alter breast conservative surgery. Methods: Twenty patients received primary CT-simulation assisted by ABC to get five sets of CT image on the three breathing condition which included one set from free breath (FB), two sets from mDIBH and two sets from deep expiration breathing control (DEBH). After radiotherapy with ten to fifteen fractions, the repeat CT-simulation was carried out to get the same five sets of CT image as the primary CT- simulation. The whole breast target were delineated at different time by the same delineator and delineated respectively by five delineators on the first set of CT images got with mDIBH from the primary CT-simulation, and to compare the influence of delineator and delineating time on the whole breast target. The total silver clips in the cavity were marked respectively on the two sets of CT images got with mDIBH from the primary CT-simulation, and to compare the intrafraction displacement of geometric body structured by the total of silver clips. The two ribs near the isocentric plane of the breast target were delineated respectively on two sets of the mDIBH CT image from the primary CT-simulation and on one set of the mDIBH CT image from the repeat CT-simulation, and comparing the movement of the point of interest (POI) of the ribs delineated to get the value of intrafraction and interfraction thoracic expansion. Results: There was not statistically significant between the four volumes of whole breast targets delineated by the same delineator at different time, but with statistics significant between the volumes of whole breast target delineated by the different delineators ( F=19.681, P=0.000). There was not statistically

  19. Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency

    International Nuclear Information System (INIS)

    Meier, U.T.; Meyer, U.A.

    1987-01-01

    The metabolism of the anticonvulsant mephenytoin is subject to a genetic polymorphism. In 2-5% of Caucasians and 18-23% of Japanese subjects a specific cytochrome P-450 isozyme, P-450 meph, is functionally deficient or missing. The authors have accumulated evidence that autoimmune antibodies observed in sera of patients with tienilic acid induced hepatitis (anti-liver kidney microsome 2 or anti-LKM2 antibodies) specifically recognize the cytochrome P-450 involved in the mephrenytoin hydroxylation polymorphism. This is demonstrated by immunoinhibition and immunoprecipitation of microsomal (S)-mephenytoin 4-hydroxylation activity and by the recognition by anti-LKM2 antibodies of a single [ 125 I]-protein band on immunoblots of human liver microsomes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis or isoelectric focusing. The cytochrome P-450 recognized by anti-LKM2 antibodies was immunopurified from microsomes derived from livers of extensive (EM) or poor metabolizers (PM) of (S)-mephenytoin. Comparison of the EM-type cytochrome P-450 to that isolated from PM livers revealed no difference in regard to immuno-cross-reactivity, molecular weight, isoelectric point, relative content in microsomes, two-dimensional tryptic peptide maps, one-dimensional peptide maps with three proteases, amino acid composition, and amino-terminal protein sequence. Finally, the same protein was precipitated from microsomes prepared from the liver biopsy of a subject phenotyped in vivo as a poor metabolizer of mephenytoin. These data strongly suggest that the mephenytoin hydroxylation deficiency is caused by a minor structural change leading to a functionally altered cytochrome P-450 isozyme

  20. Aspen Delineation - Klamath National Forest, EUI [ds368

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of known aspen stands where aspen assessments were collected in the Klamath National Forest, Siskiyou County, California. The...

  1. Genes e epilepsia I: epilepsia e alterações genéticas Genes and epilepsy I: epilepsy and genetic alterations

    Directory of Open Access Journals (Sweden)

    Daniel L. G. Gitaí

    2008-06-01

    hypersynchronous electrical activity, preferentially in cortical areas, caused by panoply of structural and neurochemical dysfunctions. Recent advances in the field have focused on the molecular mechanisms involved in the epileptogenic process. OBJECTIVES: In the present review, we describe the main genetic alterations associated to the process of epileptogenesis and discuss the new findings that are shedding light on the molecular substrates of monogenic idiopathic epilepsies (MIE and on genetically complex epilepsies (GCE. RESULTS AND CONCLUSION: Linkage and association studies have shown that mutations in ion channel genes are the main causes of MIE and of predisposition for GCE. Moreover, mutations in genes involved in neuronal migration, glycogen metabolism and respiratory chain are associated to other syndromes involving seizures. Therefore, different gene classes contribute to the epileptic trait. The identification of epilepsy-related gene families can help us understand the molecular mechanisms of neuronal hyperexcitability and recognize markers of early diagnosis as well as new treatments for these epilepsies.

  2. Genetic polymorphisms in 19q13.3 genes associated with alteration of repair capacity to BPDE-DNA adducts in primary cultured lymphocytes.

    Science.gov (United States)

    Xiao, Mingyang; Xiao, Sha; Straaten, Tahar van der; Xue, Ping; Zhang, Guopei; Zheng, Xiao; Zhang, Qianye; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Zhu, Guolian; Lu, Xiaobo

    2016-12-01

    Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Radiation protection philosophy alters

    International Nuclear Information System (INIS)

    Firmin, G.

    1977-01-01

    Two significant events that have taken place this year in the field of radiation protection are reported. New SI units have been proposed (and effectively adopted), and the ICRP has revised its recommendations. Changes of emphasis in the latest recommendations (ICRP Publication 26) imply an altered radiation protection philosophy, in particular the relation of dose limits to estimates of average risk, an altered view of the critical organ approach and a new attitude to genetic dose to the population. (author)

  4. Improved business driveway delineation in urban work zones.

    Science.gov (United States)

    2015-04-01

    This report documents the efforts and results of a two-year research project aimed at improving driveway : delineation in work zones. The first year of the project included a closed-course study to identify the most : promising driveway delineation a...

  5. 12 CFR 345.41 - Assessment area delineation.

    Science.gov (United States)

    2010-01-01

    ... the bank's delineation of its assessment area(s) as a separate performance criterion, but the FDIC..., such as those consumer loans on which the bank elects to have its performance assessed). (d... area(s) delineated by a bank in its evaluation of the bank's CRA performance unless the FDIC determines...

  6. 12 CFR 228.41 - Assessment area delineation.

    Science.gov (United States)

    2010-01-01

    ... does not evaluate the bank's delineation of its assessment area(s) as a separate performance criterion..., such as those consumer loans on which the bank elects to have its performance assessed). (d... area(s) delineated by a bank in its evaluation of the bank's CRA performance unless the Board...

  7. Genetics Home Reference: isolated ectopia lentis

    Science.gov (United States)

    ... a common feature of genetic syndromes such as Marfan syndrome and Weill-Marchesani syndrome . Enlarge Frequency The prevalence ... 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus ...

  8. Gas seepage from Tokamachi mud volcanoes, onshore Niigata Basin (Japan): Origin, post-genetic alterations and CH{sub 4}-CO{sub 2} fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Etiope, G., E-mail: etiope@ingv.it [Istituto Nazionale di Geofisica e Vulcanologia, via V. Murata 605, 00143 Roma (Italy); Nakada, R. [Dept. of Earth and Planetary Systems Science, Graduate School of Science, Hiroshima University (Japan); Tanaka, K. [Graduate School of Science and Engineering, Yamaguchi University (Japan); Yoshida, N. [Dept. of Environmental Chemistry and Engineering, Tokyo Institute of Technology (Japan)

    2011-03-15

    Research highlights: {yields} Tokamachi gas shows signals of subsurface hydrocarbon biodegradation. {yields} Hydrocarbon molecular fractionation depends on gas flux. {yields} Substantial gas emission from mud volcanoes is from invisible diffuse seepage. {yields} Global mud volcano methane emission is likely higher than 10 Mt a{sup -1}. - Abstract: Methane and CO{sub 2} emissions from the two most active mud volcanoes in central Japan, Murono and Kamou (Tokamachi City, Niigata Basin), were measured in from both craters or vents (macro-seepage) and invisible exhalation from the soil (mini- and microseepage). Molecular and isotopic compositions of the released gases were also determined. Gas is thermogenic ({delta}{sup 13}C{sub CH4} from -32.9 per mille to -36.2 per mille), likely associated with oil, and enrichments of {sup 13}C in CO{sub 2} ({delta}{sup 13}C{sub CO2} up to +28.3 per mille) and propane ({delta}{sup 13}C{sub C3H8} up to -8.6 per mille) suggest subsurface petroleum biodegradation. Gas source and post-genetic alteration processes did not change from 2004 to 2010. Methane flux ranged within the orders of magnitude of 10{sup 1}-10{sup 4} g m{sup -2} d{sup -1} in macro-seeps, and up to 446 g m{sup -2} d{sup -1} from diffuse seepage. Positive CH{sub 4} fluxes from dry soil were widespread throughout the investigated areas. Total CH{sub 4} emission from Murono and Kamou were estimated to be at least 20 and 3.7 ton a{sup -1}, respectively, of which more than half was from invisible seepage surrounding the mud volcano vents. At the macro-seeps, CO{sub 2} fluxes were directly proportional to CH{sub 4} fluxes, and the volumetric ratios between CH{sub 4} flux and CO{sub 2} flux were similar to the compositional CH{sub 4}/CO{sub 2} volume ratio. Macro-seep flux data, in addition to those of other 13 mud volcanoes, supported the hypothesis that molecular fractionation (increase of the 'Bernard ratio' C{sub 1}/(C{sub 2} + C{sub 3})) is inversely

  9. Slic Superpixels for Object Delineation from Uav Data

    Science.gov (United States)

    Crommelinck, S.; Bennett, R.; Gerke, M.; Koeva, M. N.; Yang, M. Y.; Vosselman, G.

    2017-08-01

    Unmanned aerial vehicles (UAV) are increasingly investigated with regard to their potential to create and update (cadastral) maps. UAVs provide a flexible and low-cost platform for high-resolution data, from which object outlines can be accurately delineated. This delineation could be automated with image analysis methods to improve existing mapping procedures that are cost, time and labor intensive and of little reproducibility. This study investigates a superpixel approach, namely simple linear iterative clustering (SLIC), in terms of its applicability to UAV data. The approach is investigated in terms of its applicability to high-resolution UAV orthoimages and in terms of its ability to delineate object outlines of roads and roofs. Results show that the approach is applicable to UAV orthoimages of 0.05 m GSD and extents of 100 million and 400 million pixels. Further, the approach delineates the objects with the high accuracy provided by the UAV orthoimages at completeness rates of up to 64 %. The approach is not suitable as a standalone approach for object delineation. However, it shows high potential for a combination with further methods that delineate objects at higher correctness rates in exchange of a lower localization quality. This study provides a basis for future work that will focus on the incorporation of multiple methods for an interactive, comprehensive and accurate object delineation from UAV data. This aims to support numerous application fields such as topographic and cadastral mapping.

  10. Metal artefact reduction for accurate tumour delineation in radiotherapy

    DEFF Research Database (Denmark)

    Kovacs, David Gergely; Rechner, Laura A.; Appelt, Ane L.

    2018-01-01

    Background and purpose: Two techniques for metal artefact reduction for computed tomography were studied in order to identify their impact on tumour delineation in radiotherapy. Materials and methods: Using specially designed phantoms containing metal implants (dental, spine and hip) as well...... delineation significantly (pmetal implant....... as patient images, we investigated the impact of two methods for metal artefact reduction on (A) the size and severity of metal artefacts and the accuracy of Hounsfield Unit (HU) representation, (B) the visual impact of metal artefacts on image quality and (C) delineation accuracy. A metal artefact reduction...

  11. Microbial species delineation using whole genome sequences.

    Science.gov (United States)

    Varghese, Neha J; Mukherjee, Supratim; Ivanova, Natalia; Konstantinidis, Konstantinos T; Mavrommatis, Kostas; Kyrpides, Nikos C; Pati, Amrita

    2015-08-18

    Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Delineating SPTAN1 associated phenotypes: from isolated epilepsy to encephalopathy with progressive brain atrophy.

    Science.gov (United States)

    Syrbe, Steffen; Harms, Frederike L; Parrini, Elena; Montomoli, Martino; Mütze, Ulrike; Helbig, Katherine L; Polster, Tilman; Albrecht, Beate; Bernbeck, Ulrich; van Binsbergen, Ellen; Biskup, Saskia; Burglen, Lydie; Denecke, Jonas; Heron, Bénédicte; Heyne, Henrike O; Hoffmann, Georg F; Hornemann, Frauke; Matsushige, Takeshi; Matsuura, Ryuki; Kato, Mitsuhiro; Korenke, G Christoph; Kuechler, Alma; Lämmer, Constanze; Merkenschlager, Andreas; Mignot, Cyril; Ruf, Susanne; Nakashima, Mitsuko; Saitsu, Hirotomo; Stamberger, Hannah; Pisano, Tiziana; Tohyama, Jun; Weckhuysen, Sarah; Werckx, Wendy; Wickert, Julia; Mari, Francesco; Verbeek, Nienke E; Møller, Rikke S; Koeleman, Bobby; Matsumoto, Naomichi; Dobyns, William B; Battaglia, Domenica; Lemke, Johannes R; Kutsche, Kerstin; Guerrini, Renzo

    2017-09-01

    De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non-erythrocyte αII spectrin, have been associated with severe West syndrome with hypomyelination and pontocerebellar atrophy. We aimed at comprehensively delineating the phenotypic spectrum associated with SPTAN1 mutations. Using different molecular genetic techniques, we identified 20 patients with a pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical, genetic and imaging data. SPTAN1 de novo alterations included seven unique missense variants and nine in-frame deletions/duplications of which 12 were novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred in five patients. Our patient cohort exhibited a broad spectrum of neurodevelopmental phenotypes, comprising six patients with mild to moderate intellectual disability, with or without epilepsy and behavioural disorders, and 14 patients with infantile epileptic encephalopathy, of which 13 had severe neurodevelopmental impairment and four died in early childhood. Imaging studies suggested that the severity of neurological impairment and epilepsy correlates with that of structural abnormalities as well as the mutation type and location. Out of seven patients harbouring mutations outside the α/β spectrin heterodimerization domain, four had normal brain imaging and three exhibited moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients with mutations located within the spectrin heterodimer contact site exhibited severe and progressive brain, brainstem and cerebellar atrophy, with hypomyelination in most. We used fibroblasts from five patients to study spectrin aggregate formation by Triton-X extraction and immunocytochemistry followed by fluorescence microscopy. αII/βII aggregates and αII spectrin in the insoluble protein fraction were observed in fibroblasts derived from patients with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and p.(Arg2308_Met2309dup

  13. Evaluation of genetically altered medflies for use in sterile insect technique programmes. Proceedings of the final research co-ordination meeting

    International Nuclear Information System (INIS)

    1997-01-01

    Although the medfly is a key pest in many areas of the world, there are important fruit growing areas where other fruit flies are key pests. It was concluded that it would be of value for any future CRP on genetic sexing to include these species. For the development of genetic sexing systems in these species much can be gained from the experiences with the medfly. However, at present, a similar procedure will have to be followed which will entail the construction of genetic maps, the development of cytological techniques and the induction of male linked translocation. In future, the availability of molecular methods could enable sexing systems to be transferred between species. The proceedings contain 11 papers, which range from an initial molecular analysis of the genome of the fly to a field experiment to assess the impact of an all-male release

  14. Remote sensing application for delineating coastal vegetation - A case study

    Digital Repository Service at National Institute of Oceanography (India)

    Kunte, P.D.; Wagle, B.G.

    Remote sensing data has been used for mapping coastal vegetation along the Goa Coast, India. The study envisages the use of digital image processing techniques for delineating geomorphic features and associated vegetation, including mangrove, along...

  15. Aspen Delineation - Plumas National Forest, FRRD [ds376

    Data.gov (United States)

    California Natural Resource Agency — The database represents delineations of aspen stands associated with stand assessment data (PLUMAS_NF_FEATHERRIVER_PTS) collected in aspen stands in the Plumas...

  16. Delineating social network data anonymization via random edge perturbation

    KAUST Repository

    Xue, Mingqiang; Karras, Panagiotis; Raï ssi, Chedy; Kalnis, Panos; Pung, Hungkeng

    2012-01-01

    study of the probability of success of any}structural attack as a function of the perturbation probability. Our analysis provides a powerful tool for delineating the identification risk of perturbed social network data; our extensive experiments

  17. Perioperative Clinical Nurse Specialist Role Delineation: A Systematic Review

    National Research Council Canada - National Science Library

    Cole, Lisa M; Walker, Theodore J; Nader, Kelly C; Glover, Dennis E; Newkirk, Laura E

    2006-01-01

    A clearly defined role of the Perioperative Clinical Nurse Specialist (PONS) is not identified. The purpose of this study was to provide recommendations for a delineated role of the PONS that will provide role clarity and practice guidance...

  18. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    DEFF Research Database (Denmark)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J

    2015-01-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset....

  19. Interobserver delineation variation in lung tumour stereotacticbody radiotherapy

    DEFF Research Database (Denmark)

    Persson, G. F.; Nygaard, D. E.; Hollensen, Christian

    2012-01-01

    the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design. Methods 22 consecutive patients with 26 tumours were included. Positron emission tomography/CT scans were acquired for planning of SBRT. Three oncologists and three......-sectional analysis of delineation variation for peripheral lung tumours referred for SBRT, establishing the evidence that interobserver variation is very small for these tumours....

  20. Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in wag/rij rats with genetic absence epilepsy

    NARCIS (Netherlands)

    Sarkisova, K.Y.; Midzyanovskaya, I.S.; Kulikov, M.A.; Luijtelaar, E.L.J.M. van; Luijtelaar, E.L.J.M. van; Kuznetsova, G.D.; Coenen, A.M.L.; Chepurnov, S.A.

    2004-01-01

    A Wistar derived inbred line, the WAG/Rij rats, genetically absence epilepsy prone, and their normal counterparts, outbred Wistar rats, were compared in respect to differences in behavior, in acute and chronic antidepressant imipramine treatment and in the immediate early gene c-fos expression in

  1. Transit Traffic Analysis Zone Delineating Method Based on Thiessen Polygon

    Directory of Open Access Journals (Sweden)

    Shuwei Wang

    2014-04-01

    Full Text Available A green transportation system composed of transit, busses and bicycles could be a significant in alleviating traffic congestion. However, the inaccuracy of current transit ridership forecasting methods is imposing a negative impact on the development of urban transit systems. Traffic Analysis Zone (TAZ delineating is a fundamental and essential step in ridership forecasting, existing delineating method in four-step models have some problems in reflecting the travel characteristics of urban transit. This paper aims to come up with a Transit Traffic Analysis Zone delineation method as supplement of traditional TAZs in transit service analysis. The deficiencies of current TAZ delineating methods were analyzed, and the requirements of Transit Traffic Analysis Zone (TTAZ were summarized. Considering these requirements, Thiessen Polygon was introduced into TTAZ delineating. In order to validate its feasibility, Beijing was then taken as an example to delineate TTAZs, followed by a spatial analysis of office buildings within a TTAZ and transit station departure passengers. Analysis result shows that the TTAZs based on Thiessen polygon could reflect the transit travel characteristic and is of in-depth research value.

  2. Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling.

    Science.gov (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Leto, Filippo; Cassarà, Filippo; Cannata, Monica; Maggio, Aurelio; Giambona, Antonino

    2015-04-01

    Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three β hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. This work allowed us to describe the co-inheritance of three rare β hemoglobin variants with other alterations in globin genes: the β hemoglobin variant Hb Yaounde [β134(H12)Val>Ala], found for the first time in combination with ααα(anti3.7) arrangement, and the β hemoglobin variants Hb Görwihl [β5(A2)Pro>Ala] and Hb City of Hope [β69(E13)Gly>Ser], found both in association with β(0) -thalassemia. The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca Managò

    2016-08-01

    Full Text Available Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia.

  4. Genetic Modification of Lignin in Hybrid Poplar (Populus alba × Populus tremula) Does Not Substantially Alter Plant Defense or Arthropod Communities.

    Science.gov (United States)

    Buhl, Christine; Meilan, Richard; Lindroth, Richard L

    2017-05-01

    Lignin impedes access to cellulose during biofuel production and pulping but trees can be genetically modified to improve processing efficiency. Modification of lignin may have nontarget effects on mechanical and chemical resistance and subsequent arthropod community responses with respect to pest susceptibility and arthropod biodiversity. We quantified foliar mechanical and chemical resistance traits in lignin-modified and wild-type (WT) poplar (Populus alba × Populus tremula) grown in a plantation and censused arthropods present on these trees to determine total abundance, as well as species richness, diversity and community composition. Our results indicate that mechanical resistance was not affected by lignin modification and only one genetic construct resulted in a (modest) change in chemical resistance. Arthropod abundance and community composition were consistent across modified and WT trees, but transgenics produced using one construct exhibited higher species richness and diversity relative to the WT. Our findings indicate that modification of lignin in poplar does not negatively affect herbivore resistance traits or arthropod community response, and may even result in a source of increased genetic diversity in trees and arthropod communities. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  5. Genetic deletion of P-glycoprotein alters stress responsivity and increases depression-like behavior, social withdrawal and microglial activation in the hippocampus of female mice.

    Science.gov (United States)

    Brzozowska, Natalia I; Smith, Kristie L; Zhou, Cilla; Waters, Peter M; Cavalcante, Ligia Menezes; Abelev, Sarah V; Kuligowski, Michael; Clarke, David J; Todd, Stephanie M; Arnold, Jonathon C

    2017-10-01

    P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors. Female P-gp knockout mice displayed an unusual, frantic anxiety response to intraperitoneal injection stress in the light-dark test. They also tended to display reduced conditioned fear responses compared to wild-type (WT) mice in a paradigm where a single electric foot-shock stressor was paired to a context. Foot-shock stress reduced social interaction and decreased microglia cell density in the amygdala which was not varied by P-gp genotype. Independently of stressor exposure, female P-gp deficient mice displayed increased depression-like behavior, idiosyncratic darting behavior, age-related social withdrawal and hyperactivity, facilitated sensorimotor gating and altered startle reactivity. In addition, P-gp deletion increased microglia cell density in the CA3 region of the hippocampus, and the microglial cells exhibited a reactive, hypo-ramified morphology. Further, female P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the hippocampus. In conclusion, this research shows that germline P-gp deletion affected various behaviors of relevance to psychiatric conditions, and that altered microglial cell activity and enhanced GR expression in the hippocampus may play a role in mediating these behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. | Office of Cancer Genomics

    Science.gov (United States)

    A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers.

  7. In vitro short-term exposure to air pollution PM{sub 2.5-0.3} induced cell cycle alterations and genetic instability in a human lung cell coculture model

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Imane [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Lebanese Atomic Energy Commission – CNRS, Beirut (Lebanon); Verdin, Anthony [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Escande, Fabienne [Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire, Lille (France); Saint-Georges, Françoise [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Cazier, Fabrice [Université de Lille, Lille (France); Centre Commun de Mesures, Université du Littoral-Côte d’Opale, Dunkerque (France); Mulliez, Philippe [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); Courcot, Dominique; Shirali, Pirouz [Université de Lille, Lille (France); EA4492-UCEIV, Université du Littoral-Côte d’Opale, Dunkerque (France); Gosset, Pierre [Université de Lille, Lille (France); Groupement Hospitalier de l’Institut Catholique de Lille, Lille (France); and others

    2016-05-15

    Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM{sub 2.5-0.3}-exposed coculture model. PM{sub 2.5-0.3} exposure of human AM from the coculture model induced marked cell cycle alterations after 24 h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM{sub 2.5-0.3} was reported in the L132 cells. Exposure of human AM from the coculture model to PM{sub 2.5-0.3} resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM{sub 2.5-0.3} induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability. - Highlights: • Better knowledge on health adverse effects of air pollution PM{sub 2.5}. • Human alveolar macrophage and normal human epithelial lung cell coculture. • Molecular abnormalities from TP53-RB gene signaling pathway. • Loss of heterozygosity and microsatellite instability. • Pathologic changes in morphology and number of cells in relation to airway remodeling.

  8. Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

    Science.gov (United States)

    Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

    2012-05-01

    Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

  9. Altered Tuber Yield in Genetically Modified High-Amylose and Oil Potato Lines Is Associated With Changed Whole-Plant Nitrogen Economy

    Directory of Open Access Journals (Sweden)

    Fereshteh Pourazari

    2018-03-01

    Full Text Available Breeding for improved crop quality traits can affect non-target traits related to growth and resource use, and these effects may vary in different cultivation conditions (e. g., greenhouse vs. field. The objectives of this study are to investigate the growth and whole-plant nitrogen (N economy of two genetically modified (GM potato lines compared to their non-GM parental varieties and when grown in different cultivation conditions. A high-amylose GM potato line and its parent were grown under field and greenhouse conditions for one growing season in Sweden; and a GM oil potato line and its parent were grown in greenhouse conditions only. Tuber yield, above ground biomass, N uptake efficiency and other plant N economy traits were assessed. In both cultivation conditions, the GM lines produced between 1.5 and two times more tubers as compared with their parents. In the greenhouse, fresh tuber yield and N uptake efficiency were unaffected by the genetic modifications, but the GM-lines produced less tuber biomass per plant-internal N compared to their parents. In the field, the fresh tuber yield was 40% greater in the high-amylose line as compared with its parent; the greater fresh tuber yield in the high-amylose GM line was accomplished by higher water allocation to the harvested tubers, and associated with increased N recovery from soil (+20%, N uptake efficiency (+53%, tuber N content (+20%, and N accumulation (+120% compared with the non-GM parent. The cultivation conditions influenced the yield and N economy. For example, the final fresh above-ground plant biomass and N pool were considerably higher in the greenhouse conditions, whilst the tuber yield was higher in the field conditions. In conclusion, the genetic modification inducing high accumulation of amylose in potato tubers affected several non-target traits related to plant N economy, and increased the plant N uptake and accumulation efficiency of the field-grown plants. Due to strongly

  10. Altered Tuber Yield in Genetically Modified High-Amylose and Oil Potato Lines Is Associated With Changed Whole-Plant Nitrogen Economy.

    Science.gov (United States)

    Pourazari, Fereshteh; Andersson, Mariette; Weih, Martin

    2018-01-01

    Breeding for improved crop quality traits can affect non-target traits related to growth and resource use, and these effects may vary in different cultivation conditions (e. g., greenhouse vs. field). The objectives of this study are to investigate the growth and whole-plant nitrogen (N) economy of two genetically modified (GM) potato lines compared to their non-GM parental varieties and when grown in different cultivation conditions. A high-amylose GM potato line and its parent were grown under field and greenhouse conditions for one growing season in Sweden; and a GM oil potato line and its parent were grown in greenhouse conditions only. Tuber yield, above ground biomass, N uptake efficiency and other plant N economy traits were assessed. In both cultivation conditions, the GM lines produced between 1.5 and two times more tubers as compared with their parents. In the greenhouse, fresh tuber yield and N uptake efficiency were unaffected by the genetic modifications, but the GM-lines produced less tuber biomass per plant-internal N compared to their parents. In the field, the fresh tuber yield was 40% greater in the high-amylose line as compared with its parent; the greater fresh tuber yield in the high-amylose GM line was accomplished by higher water allocation to the harvested tubers, and associated with increased N recovery from soil (+20%), N uptake efficiency (+53%), tuber N content (+20%), and N accumulation (+120%) compared with the non-GM parent. The cultivation conditions influenced the yield and N economy. For example, the final fresh above-ground plant biomass and N pool were considerably higher in the greenhouse conditions, whilst the tuber yield was higher in the field conditions. In conclusion, the genetic modification inducing high accumulation of amylose in potato tubers affected several non-target traits related to plant N economy, and increased the plant N uptake and accumulation efficiency of the field-grown plants. Due to strongly increased

  11. Two genetic determinants acquired late in Mus evolution regulate the inclusion of exon 5, which alters mouse APOBEC3 translation efficiency.

    Directory of Open Access Journals (Sweden)

    Jun Li

    2012-01-01

    Full Text Available Mouse apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like editing complex 3 (mA3, an intracellular antiviral factor, has 2 allelic variations that are linked with different susceptibilities to beta- and gammaretrovirus infections among various mouse strains. In virus-resistant C57BL/6 (B6 mice, mA3 transcripts are more abundant than those in susceptible BALB/c mice both in the spleen and bone marrow. These strains of mice also express mA3 transcripts with different splicing patterns: B6 mice preferentially express exon 5-deficient (Δ5 mA3 mRNA, while BALB/c mice produce exon 5-containing full-length mA3 mRNA as the major transcript. Although the protein product of the Δ5 mRNA exerts stronger antiretroviral activities than the full-length protein, how exon 5 affects mA3 antiviral activity, as well as the genetic mechanisms regulating exon 5 inclusion into the mA3 transcripts, remains largely uncharacterized. Here we show that mA3 exon 5 is indeed a functional element that influences protein synthesis at a post-transcriptional level. We further employed in vitro splicing assays using genomic DNA clones to identify two critical polymorphisms affecting the inclusion of exon 5 into mA3 transcripts: the number of TCCT repeats upstream of exon 5 and the single nucleotide polymorphism within exon 5 located 12 bases upstream of the exon 5/intron 5 boundary. Distribution of the above polymorphisms among different Mus species indicates that the inclusion of exon 5 into mA3 mRNA is a relatively recent event in the evolution of mice. The widespread geographic distribution of this exon 5-including genetic variant suggests that in some Mus populations the cost of maintaining an effective but mutagenic enzyme may outweigh its antiviral function.

  12. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

    2004-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  13. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Lu, Mei

    2006-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  14. Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration.

    Science.gov (United States)

    Powis, Zöe; Hart, Alexa; Cherny, Sara; Petrik, Igor; Palmaer, Erika; Tang, Sha; Jones, Carolyn

    2017-06-02

    Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient. Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava. DES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.

  15. Automated delineation of stroke lesions using brain CT images

    Directory of Open Access Journals (Sweden)

    Céline R. Gillebert

    2014-01-01

    Full Text Available Computed tomographic (CT images are widely used for the identification of abnormal brain tissue following infarct and hemorrhage in stroke. Manual lesion delineation is currently the standard approach, but is both time-consuming and operator-dependent. To address these issues, we present a method that can automatically delineate infarct and hemorrhage in stroke CT images. The key elements of this method are the accurate normalization of CT images from stroke patients into template space and the subsequent voxelwise comparison with a group of control CT images for defining areas with hypo- or hyper-intense signals. Our validation, using simulated and actual lesions, shows that our approach is effective in reconstructing lesions resulting from both infarct and hemorrhage and yields lesion maps spatially consistent with those produced manually by expert operators. A limitation is that, relative to manual delineation, there is reduced sensitivity of the automated method in regions close to the ventricles and the brain contours. However, the automated method presents a number of benefits in terms of offering significant time savings and the elimination of the inter-operator differences inherent to manual tracing approaches. These factors are relevant for the creation of large-scale lesion databases for neuropsychological research. The automated delineation of stroke lesions from CT scans may also enable longitudinal studies to quantify changes in damaged tissue in an objective and reproducible manner.

  16. Delineation of seismic source zones based on seismicity parameters ...

    Indian Academy of Sciences (India)

    In the present study, an attempt has been made to delineate seismic source zones in the study area (south India) based on the seismicity parameters. Seismicity parameters and the maximum probable earthquake for these source zones were evaluated and were used in the hazard evaluation. The probabilistic evaluation of ...

  17. Delineating psychomotor slowing from reduced processing speed in schizophrenia

    NARCIS (Netherlands)

    Morrens, M.; Hulstijn, W.; Matton, C.; Madani, Y.; Bouwel, L. van; Peuskens, J.; Sabbe, B.G.C.

    2008-01-01

    Introduction. Psychomotor slowing is an intrinsic feature of schizophrenia that is poorly delineated from generally reduced processing speed. Although the Symbol Digit Substitution Test (SDST) is widely used to assess psychomotor speed, the task also taps several higher-order cognitive processes.

  18. subsurface sequence delineation and saline water mapping of lagos

    African Journals Online (AJOL)

    A subsurface sequence delineation and saline water mapping of Lagos State was carried out. Ten (10) deep boreholes with average depth of 300 m were drilled within the sedimentary basin. The boreholes were lithologically and geophysically logged. The driller's lithological logs aided by gamma and resistivity logs, ...

  19. A novel algorithm for delineating wetland depressions and ...

    Science.gov (United States)

    In traditional watershed delineation and topographic modeling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM) to enforce flow continuity of water across the topographic surface to the watershed outlets. In reality, however, many depressions in the DEM are actual wetland landscape features that are seldom fully filled with water. For instance, wetland depressions in the Prairie Pothole Region (PPR) are seasonally to permanently flooded wetlands characterized by nested hierarchical structures with dynamic filling- spilling-merging surface-water hydrological processes. The objectives of this study were to delineate hierarchical wetland catchments and model their hydrologic connectivity using high-resolution LiDAR data and aerial imagery. We proposed a novel algorithm delineate the hierarchical wetland catchments and characterize their geometric and topological properties. Potential hydrologic connectivity between wetlands and streams were simulated using the least-cost path algorithm. The resulting flow network delineated putative temporary or seasonal flow paths connecting wetland depressions to each other or to the river network at scales finer than available through the National Hydrography Dataset. The results demonstrated that our proposed framework is promising for improving overland flow modeling and hydrologic connectivity analysis. Presentation at AWRA Spring Specialty Conference in Sn

  20. Riparian ecotone: A functional definition and delineation for resource assessment

    Science.gov (United States)

    E. S Verry; C. A Dolloff; M. E. Manning

    2004-01-01

    We propose a geomorphic basis for defining riparian areas using the term: riparian ecotone, discuss how past definitions fall short, and illustrate how a linked sequence of definition, delineation, and riparian sampling are used to accurately assess riparian resources on the ground. Our riparian ecotone is based on the width of the valley (its floodprone area width)...

  1. Effects of data resolution and stream delineation threshold area on ...

    African Journals Online (AJOL)

    The results also indicate that peak flow and slope of the hydrograph rising limb obtained from the SRTM DEM at different threshold areas (ranging from 0.25% to 3%) are greater than that for the TOPO DEM. Investigating the effects of stream network delineation threshold area on the simulated peak flow shows that the ...

  2. Nicolaides-Baraitser Syndrome : Delineation of the Phenotype

    NARCIS (Netherlands)

    Sousa, Sergio B.; Abdul-Rahman, Omar A.; Bottani, Armand; Cormier-Daire, Valerie; Fryer, Alan; Gillessen-Kaesbach, Gabriele; Horn, Denise; Josifova, Dragana; Kuechler, Alma; Lees, Melissa; MacDermot, Kay; Magee, Alex; Morice-Picard, Fanny; Rosser, Elizabeth; Sarkar, Ajoy; Shannon, Nora; Stolte-Dijkstra, Irene; Verloes, Alain; Wakeling, Emma; Wilson, Louise; Hennekam, Raoul C. M.

    Nicolaides-Baraitser syndrome (NBS) is an infrequently described condition, thus far reported in five cases. In order to delineate the phenotype and its natural history in more detail, we gathered data on 18 hitherto unreported patients through a multi-center collaborative study, and follow-up data

  3. Nicolaides-Baraitser Syndrome: Delineation of the Phenotype

    NARCIS (Netherlands)

    Sousa, Sérgio B.; Abdul-Rahman, Omar A.; Bottani, Armand; Cormier-Daire, Valérie; Fryer, Alan; Gillessen-Kaesbach, Gabriele; Horn, Denise; Josifova, Dragana; Kuechler, Alma; Lees, Melissa; Macdermot, Kay; Magee, Alex; Morice-Picard, Fanny; Rosser, Elizabeth; Sarkar, Ajoy; Shannon, Nora; Stolte-Dijkstra, Irene; Verloes, Alain; Wakeling, Emma; Wilson, Louise; Hennekam, Raoul C. M.

    2009-01-01

    Nicolaides-Baraitser syndrome (NBS) is an infrequently described condition, thus far reported in five cases. In order to delineate the phenotype and its natural history in more detail, we gathered data on 18 hitherto unreported patients through a multi-center collaborative study, and follow-up data

  4. The Regionalization of Africa: Delineating Africa's Subregions Using Airline Data

    Science.gov (United States)

    Good, Pieter R.; Derudder, Ben; Witlox, Frank J.

    2011-01-01

    Current regionalizations of Africa have limitations in that they are attribute-based and regions are delineated according to national boundaries. Taking the world city network approach as starting point, it is possible to use relational data (i.e., information about the relationships between cities) rather than attribute data, and moreover, it…

  5. Evaluation of Peritumoral Edema in the Delineation of Radiotherapy Clinical Target Volumes for Glioblastoma

    International Nuclear Information System (INIS)

    Chang, Eric L.; Akyurek, Serap; Avalos, Tedde C; Rebueno, Neal C; Spicer, Chris C; Garcia, John C; Famiglietti, Robin; Allen, Pamela K.; Chao, K.S. Clifford; Mahajan, Anita; Woo, Shiao Y.; Maor, Moshe H.

    2007-01-01

    Purpose: To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM). Methods and Materials: Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms. Results: A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r 2 0.0007; p = 0.3). For patients with edema >75 cm 3 , the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence). Conclusion: Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm 3 , using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema

  6. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

    Science.gov (United States)

    Bečanović, Kristina; Nørremølle, Anne; Neal, Scott J; Kay, Chris; Collins, Jennifer A; Arenillas, David; Lilja, Tobias; Gaudenzi, Giulia; Manoharan, Shiana; Doty, Crystal N; Beck, Jessalyn; Lahiri, Nayana; Portales-Casamar, Elodie; Warby, Simon C; Connolly, Colúm; De Souza, Rebecca A G; Tabrizi, Sarah J; Hermanson, Ola; Langbehn, Douglas R; Hayden, Michael R; Wasserman, Wyeth W; Leavitt, Blair R

    2015-06-01

    Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity. A non-coding SNP, rs13102260:G > A, in this binding site impaired NF-κB binding and reduced HTT transcriptional activity and HTT protein expression. The presence of the rs13102260 minor (A) variant on the HD disease allele was associated with delayed age of onset in familial cases, whereas the presence of the rs13102260 (A) variant on the wild-type HTT allele was associated with earlier age of onset in HD patients in an extreme case-based cohort. Our findings suggest a previously unknown mechanism linking allele-specific effects of rs13102260 on HTT expression to HD age of onset and have implications for HTT silencing treatments that are currently in development.

  7. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

  8. Genetic variants associated with altered plasma levels of C-reactive protein are not associated with late-life cognitive ability in four Scottish samples.

    Science.gov (United States)

    Marioni, Riccardo E; Deary, Ian J; Murray, Gordon D; Lowe, Gordon D O; Rafnsson, Snorri B; Strachan, Mark W J; Luciano, Michelle; Houlihan, Lorna M; Gow, Alan J; Harris, Sarah E; Stewart, Marlene C; Rumley, Ann; Fowkes, F Gerry R; Price, Jackie F

    2010-01-01

    It is unknown whether the relationship between raised inflammatory biomarker levels and late-life cognitive ability is causal. We explored this issue by testing the association between genetic regulators of plasma C-reactive protein (CRP) and cognition. Data were analysed from four cohorts based in central Scotland (Total N = 4,782). Associations were tested between variants in the CRP gene and both plasma CRP levels and a battery of neuropsychological tests, including a vocabulary-based estimate of peak prior cognitive ability and a general (summary) cognitive factor score, or 'g'. CRP levels were associated with a number of variants in the CRP gene (SNPs), including rs1205, rs1130864, rs1800947, and rs1417938 (P range 4.2e-06 to 0.041). Higher CRP levels were also associated with vocabulary-adjusted cognitive ability, used here to estimate lifetime cognitive change (P range 1.7e-04 to 0.038). After correction for multiple testing and adjustment for age and sex, no statistically significant associations were found between the SNPs and cognition. CRP is unlikely to be a causal determinant of late-life cognitive ability.

  9. Suppressor T-cell factor(s) display an altered pattern of Igh (immunoglobulin heavy chain locus) genetic restriction when developed in an Igh-congeneic host

    International Nuclear Information System (INIS)

    HayGlass, K.T.; Naides, S.J.; Benacerraf, B.; Sy, M.S.

    1985-01-01

    Suppressor T cell factor(s) (TsF 1 ) inhibit the in vivo priming of azobenzenearsonate-specific cytotoxic T-cell responses. The activity of TsF 1 is restricted by genes linked to Igh-1 allotypic markers. TsF 1 obtained from B6.Igh-1/sup n/ mice was unable to suppress the immune response in B6.Igh-1/sup b/ mice and vice versa. However, TsF 1 prepared from B6.Igh-1/sup n/ T cells parked in an Igh-congeneic B6.Igh-1/sup b/ environment displays an additional restriction specificity of the host. Thus, TsF 1 prepared from these Igh-chimeric mice suppressed immune responses in both B6.Igh-1/sup n/ (donor) and B6.Igh-1/sup b/ (recipient) mice but not in mice of the unrelated strain BALB/c.Igh-1/sup a/. The results indicate that the establishment of the suppressor T-cell repertoire is dependent not only upon the genetic background of the individual T cell but also upon the influence of Igh-linked determinants present when T-cell clones are selected during the response

  10. Impact of chromosome alterations, genetic mutations and clonal hematopoiesis of indeterminate potential (CHIP) on the classification and risk stratification of MDS.

    Science.gov (United States)

    Ganguly, Bani Bandana; Banerjee, Debasis; Agarwal, Mohan B

    2018-03-01

    The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome. However, recent concepts of clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) have urged a re-definition of mutational events in non-clonal cytopenia and non-MDS healthy elderly but with a higher risk of overt leukemia. Considering gene mutations, chromosomal alterations, CHIP, ICUS and their significance in classification and risk-scoring certainly presents a comprehensive picture of disease-phenotype towards better understanding of MDS-pathogenesis, its evolution to AML and its response to therapeutic agents. The present review summarizes chromosomal and gene mutations, co-existence of mutational complexity, and WHO-2016 classification and risk-stratifications of MDS to facilitate a better understanding of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The order of exercise during concurrent training for rehabilitation does not alter acute genetic expression, mitochondrial enzyme activity or improvements in muscle function.

    Directory of Open Access Journals (Sweden)

    Lauren G MacNeil

    Full Text Available Concurrent exercise combines different modes of exercise (e.g., aerobic and resistance into one training protocol, providing stimuli meant to increase muscle strength, aerobic capacity and mass. As disuse is associated with decrements in strength, aerobic capacity and muscle size concurrent training is an attractive modality for rehabilitation. However, interference between the signaling pathways may result in preferential improvements for one of the exercise modes. We recruited 18 young adults (10 ♂, 8 ♀ to determine if order of exercise mode during concurrent training would differentially affect gene expression, protein content and measures of strength and aerobic capacity after 2 weeks of knee-brace induced disuse. Concurrent exercise sessions were performed 3x/week for 6 weeks at gradually increasing intensities either with endurance exercise preceding (END>RES or following (RES>END resistance exercise. Biopsies were collected from the vastus lateralis before, 3 h after the first exercise bout and 48 h after the end of training. Concurrent exercise altered the expression of genes involved in mitochondrial biogenesis (PGC-1α, PRC, PPARγ, hypertrophy (PGC-1α4, REDD2, Rheb and atrophy (MuRF-1, Runx1, increased electron transport chain complex protein content, citrate synthase and mitochondrial cytochrome c oxidase enzyme activity, muscle mass, maximum isometric strength and VO 2peak. However, the order in which exercise was completed (END>RES or RES>END only affected the protein content of mitochondrial complex II subunit. In conclusion, concurrent exercise training is an effective modality for the rehabilitation of the loss of skeletal muscle mass, maximum strength, and peak aerobic capacity resulting from disuse, regardless of the order in which the modes of exercise are performed.

  12. Neuropeptide S alters anxiety, but not depression-like behaviour in Flinders Sensitive Line rats: a genetic animal model of depression.

    Science.gov (United States)

    Wegener, Gregers; Finger, Beate C; Elfving, Betina; Keller, Kirsten; Liebenberg, Nico; Fischer, Christina W; Singewald, Nicolas; Slattery, David A; Neumann, Inga D; Mathé, Aleksander A

    2012-04-01

    Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behaviour in rodents. However, little knowledge is available regarding the NPS system in depression-related behaviours, and whether NPS also exerts anxiolytic effects in an animal model of psychopathology. Therefore, the aim of this work was to characterize the effects of NPS on depression- and anxiety-related parameters, using male and female rats in a well-validated animal model of depression: the Flinders Sensitive Line (FSL), their controls, the Flinders Resistant Line (FRL), and Sprague-Dawley (SD) rats. We found that FSL showed greater immobility in the forced swim test (FST) than FRL, confirming their phenotype. However, NPS did not affect depression-related behaviour in any rat line. No significant differences in baseline anxiety levels between the FSL and FRL strains were observed, but FSL and FRL rats displayed less anxiety-like behaviour compared to SD rats. NPS decreased anxiety-like behaviour on the elevated plus-maze in all strains. The expression of the NPSR in the amygdala, periventricular hypothalamic nucleus, and hippocampus was equal in all male strains, although a trend towards reduced expression within the amygdala was observed in FSL rats compared to SD rats. In conclusion, NPS had a marked anxiolytic effect in FSL, FRL and SD rats, but did not modify the depression-related behaviour in any strain, in spite of the significant differences in innate level between the strains. These findings suggest that NPS specifically modifies anxiety behaviour but cannot overcome/reverse a genetically mediated depression phenotype.

  13. Chimeric Feline Coronaviruses That Encode Type II Spike Protein on Type I Genetic Background Display Accelerated Viral Growth and Altered Receptor Usage▿

    Science.gov (United States)

    Tekes, Gergely; Hofmann-Lehmann, Regina; Bank-Wolf, Barbara; Maier, Reinhard; Thiel, Heinz-Jürgen; Thiel, Volker

    2010-01-01

    Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein. PMID:19906918

  14. Target volume delineation in external beam partial breast irradiation: Less inter-observer variation with preoperative- compared to postoperative delineation

    International Nuclear Information System (INIS)

    Leij, Femke van der; Elkhuizen, Paula H.M.; Janssen, Tomas M.; Poortmans, Philip; Sangen, Maurice van der; Scholten, Astrid N.; Vliet-Vroegindeweij, Corine van; Boersma, Liesbeth J.

    2014-01-01

    The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of twenty-four breast cancer patients

  15. Target volume delineation in external beam partial breast irradiation: less inter-observer variation with preoperative- compared to postoperative delineation

    NARCIS (Netherlands)

    Leij, F. van der; Elkhuizen, P.H.M.; Janssen, T.M.; Poortmans, P.M.P.; Sangen, M. van der; Scholten, A.N.; Vliet-Vroegindeweij, C. van; Boersma, L.J.

    2014-01-01

    The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of

  16. Delineating Neural Structures of Developmental Human Brains with Diffusion Tensor Imaging

    Directory of Open Access Journals (Sweden)

    Hao Huang

    2010-01-01

    Full Text Available The human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is a simple tubular structure. Revealing detailed anatomy at different stages of brain development not only aids in understanding this highly ordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. However, anatomical studies of human brain development during the fetal period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor imaging (DTI measures water diffusion to delineate the underlying neural structures. The high contrasts derived from DTI can be used to establish the brain atlas. With DTI tractography, coherent neural structures, such as white matter tracts, can be three-dimensionally reconstructed. The primary eigenvector of the diffusion tensor can be further explored to characterize microstructures in the cerebral wall of the developmental brains. In this mini-review, the application of DTI in order to reveal the structures of developmental fetal brains has been reviewed in the above-mentioned aspects. The fetal brain DTI provides a unique insight for delineating the neural structures in both macroscopic and microscopic levels. The resultant DTI database will provide structural guidance for the developmental study of human fetal brains in basic neuroscience, and reference standards for diagnostic radiology of premature newborns.

  17. Specificity of lipoxygenase pathways supports species delineation in the marine diatom genus Pseudo-nitzschia.

    Directory of Open Access Journals (Sweden)

    Nadia Lamari

    Full Text Available Oxylipins are low-molecular weight secondary metabolites derived from the incorporation of oxygen into the carbon chains of polyunsaturated fatty acids (PUFAs. Oxylipins are produced in many prokaryotic and eukaryotic lineages where they are involved in a broad spectrum of actions spanning from stress and defense responses, regulation of growth and development, signaling, and innate immunity. We explored the diversity in oxylipin patterns in the marine planktonic diatom Pseudo-nitzschia. This genus includes several species only distinguishable with the aid of molecular markers. Oxylipin profiles of cultured strains were obtained by reverse phase column on a liquid chromatograph equipped with UV photodiode detector and q-ToF mass spectrometer. Lipoxygenase compounds were mapped on phylogenies of the genus Pseudo-nitzschia inferred from the nuclear encoded hyper-variable region of the LSU rDNA and the plastid encoded rbcL. Results showed that the genus Pseudo-nitzschia exhibits a rich and varied lipoxygenase metabolism of eicosapentaenoic acid (EPA, with a high level of specificity for oxylipin markers that generally corroborated the genotypic delineation, even among genetically closely related cryptic species. These results suggest that oxylipin profiles constitute additional identification tools for Pseudo-nitzschia species providing a functional support to species delineation obtained with molecular markers and morphological traits. The exploration of the diversity, patterns and plasticity of oxylipin production across diatom species and genera will also provide insights on the ecological functions of these secondary metabolites and on the selective pressures driving their diversification.

  18. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors

    DEFF Research Database (Denmark)

    von Deimling, A; Fimmers, R; Schmidt, M C

    2000-01-01

    Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors....

  19. Epigenetic Alterations in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Johannes eGräff

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  20. Epigenetic Alterations in Alzheimer's Disease.

    Science.gov (United States)

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD.

  1. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  2. Delineation of gravel-bed clusters via factorial kriging

    Science.gov (United States)

    Wu, Fu-Chun; Wang, Chi-Kuei; Huang, Guo-Hao

    2018-05-01

    Gravel-bed clusters are the most prevalent microforms that affect local flows and sediment transport. A growing consensus is that the practice of cluster delineation should be based primarily on bed topography rather than grain sizes. Here we present a novel approach for cluster delineation using patch-scale high-resolution digital elevation models (DEMs). We use a geostatistical interpolation method, i.e., factorial kriging, to decompose the short- and long-range (grain- and microform-scale) DEMs. The required parameters are determined directly from the scales of the nested variograms. The short-range DEM exhibits a flat bed topography, yet individual grains are sharply outlined, making the short-range DEM a useful aid for grain segmentation. The long-range DEM exhibits a smoother topography than the original full DEM, yet groupings of particles emerge as small-scale bedforms, making the contour percentile levels of the long-range DEM a useful tool for cluster identification. Individual clusters are delineated using the segmented grains and identified clusters via a range of contour percentile levels. Our results reveal that the density and total area of delineated clusters decrease with increasing contour percentile level, while the mean grain size of clusters and average size of anchor clast (i.e., the largest particle in a cluster) increase with the contour percentile level. These results support the interpretation that larger particles group as clusters and protrude higher above the bed than other smaller grains. A striking feature of the delineated clusters is that anchor clasts are invariably greater than the D90 of the grain sizes even though a threshold anchor size was not adopted herein. The average areal fractal dimensions (Hausdorff-Besicovich dimensions of the projected areas) of individual clusters, however, demonstrate that clusters delineated with different contour percentile levels exhibit similar planform morphologies. Comparisons with a

  3. Genetic Mutations in Cancer

    Science.gov (United States)

    Many different types of genetic mutations are found in cancer cells. This infographic outlines certain types of alterations that are present in cancer, such as missense, nonsense, frameshift, and chromosome rearrangements.

  4. Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus.

    Science.gov (United States)

    Choi, Gloria B; Dong, Hong-Wei; Murphy, Andrew J; Valenzuela, David M; Yancopoulos, George D; Swanson, Larry W; Anderson, David J

    2005-05-19

    In mammals, innate reproductive and defensive behaviors are mediated by anatomically segregated connections between the amygdala and hypothalamus. This anatomic segregation poses the problem of how the brain integrates activity in these circuits when faced with conflicting stimuli eliciting such mutually exclusive behaviors. Using genetically encoded and conventional axonal tracers, we have found that the transcription factor Lhx6 delineates the reproductive branch of this pathway. Other Lhx proteins mark neurons in amygdalar nuclei implicated in defense. We have traced parallel projections from the posterior medial amygdala, activated by reproductive or defensive olfactory stimuli, respectively, to a point of convergence in the ventromedial hypothalamus. The opposite neurotransmitter phenotypes of these convergent projections suggest a "gate control" mechanism for the inhibition of reproductive behaviors by threatening stimuli. Our data therefore identify a potential neural substrate for integrating the influences of conflicting behavioral cues and a transcription factor family that may contribute to the development of this substrate.

  5. Tumor and target delineation: current research and future challenges

    International Nuclear Information System (INIS)

    Austin-Seymour, Mary; Chen, George T.Y.; Rosenman, Julian; Michalski, Jeff; Lindsley, Karen; Goitein, Michael

    1995-01-01

    In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target. The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties

  6. Crowdsourcing for error detection in cortical surface delineations.

    Science.gov (United States)

    Ganz, Melanie; Kondermann, Daniel; Andrulis, Jonas; Knudsen, Gitte Moos; Maier-Hein, Lena

    2017-01-01

    With the recent trend toward big data analysis, neuroimaging datasets have grown substantially in the past years. While larger datasets potentially offer important insights for medical research, one major bottleneck is the requirement for resources of medical experts needed to validate automatic processing results. To address this issue, the goal of this paper was to assess whether anonymous nonexperts from an online community can perform quality control of MR-based cortical surface delineations derived by an automatic algorithm. So-called knowledge workers from an online crowdsourcing platform were asked to annotate errors in automatic cortical surface delineations on 100 central, coronal slices of MR images. On average, annotations for 100 images were obtained in less than an hour. When using expert annotations as reference, the crowd on average achieves a sensitivity of 82 % and a precision of 42 %. Merging multiple annotations per image significantly improves the sensitivity of the crowd (up to 95 %), but leads to a decrease in precision (as low as 22 %). Our experiments show that the detection of errors in automatic cortical surface delineations generated by anonymous untrained workers is feasible. Future work will focus on increasing the sensitivity of our method further, such that the error detection tasks can be handled exclusively by the crowd and expert resources can be focused on error correction.

  7. Image-Based Delineation and Classification of Built Heritage Masonry

    Directory of Open Access Journals (Sweden)

    Noelia Oses

    2014-02-01

    Full Text Available Fundación Zain is developing new built heritage assessment protocols. The goal is to objectivize and standardize the analysis and decision process that leads to determining the degree of protection of built heritage in the Basque Country. The ultimate step in this objectivization and standardization effort will be the development of an information and communication technology (ICT tool for the assessment of built heritage. This paper presents the ground work carried out to make this tool possible: the automatic, image-based delineation of stone masonry. This is a necessary first step in the development of the tool, as the built heritage that will be assessed consists of stone masonry construction, and many of the features analyzed can be characterized according to the geometry and arrangement of the stones. Much of the assessment is carried out through visual inspection. Thus, this process will be automated by applying image processing on digital images of the elements under inspection. The principal contribution of this paper is the automatic delineation the framework proposed. The other contribution is the performance evaluation of this delineation as the input to a classifier for a geometrically characterized feature of a built heritage object. The element chosen to perform this evaluation is the stone arrangement of masonry walls. The validity of the proposed framework is assessed on real images of masonry walls.

  8. Tools to analyse and display variations in anatomical delineation

    International Nuclear Information System (INIS)

    Ebert, Martin A.; McDermott, L.N.; Haworth, A; Van der Wath, E.; Hooton, B.

    2012-01-01

    Variations in anatomical delineation, principally due to a combination of inter-observer contributions and image-specificity, remain one of the most significant impediments to geometrically-accurate radiotherapy. Quantification of spatial variability of the delineated contours comprising a structure can be made with a variety of metrics, and the availability of software tools to apply such metrics to data collected during inter-observer or repeat-imaging studies would allow their validation. A suite of such tools have been developed which use an Extensible Markup Language format for the exchange of delineated 3D structures with radiotherapy planning or review systems. These tools provide basic operations for manipulating and operating on individual structures and related structure sets, and for deriving statistics on spatial variations of contours that can be mapped onto the surface of a reference structure. Use of these tools on a sample dataset is demonstrated together with import and display of results in the SWAN treatment plan review system.

  9. Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

    Science.gov (United States)

    2018-01-01

    Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770

  10. Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

    Directory of Open Access Journals (Sweden)

    Roshan Dadachanji

    2018-01-01

    Full Text Available Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

  11. PET functional volume delineation: a robustness and repeatability study

    International Nuclear Information System (INIS)

    Hatt, Mathieu; Cheze-le Rest, Catherine; Albarghach, Nidal; Pradier, Olivier; Visvikis, Dimitris

    2011-01-01

    Current state-of-the-art algorithms for functional uptake volume segmentation in PET imaging consist of threshold-based approaches, whose parameters often require specific optimization for a given scanner and associated reconstruction algorithms. Different advanced image segmentation approaches previously proposed and extensively validated, such as among others fuzzy C-means (FCM) clustering, or fuzzy locally adaptive bayesian (FLAB) algorithm have the potential to improve the robustness of functional uptake volume measurements. The objective of this study was to investigate robustness and repeatability with respect to various scanner models, reconstruction algorithms and acquisition conditions. Robustness was evaluated using a series of IEC phantom acquisitions carried out on different PET/CT scanners (Philips Gemini and Gemini Time-of-Flight, Siemens Biograph and GE Discovery LS) with their associated reconstruction algorithms (RAMLA, TF MLEM, OSEM). A range of acquisition parameters (contrast, duration) and reconstruction parameters (voxel size) were considered for each scanner model, and the repeatability of each method was evaluated on simulated and clinical tumours and compared to manual delineation. For all the scanner models, acquisition parameters and reconstruction algorithms considered, the FLAB algorithm demonstrated higher robustness in delineation of the spheres with low mean errors (10%) and variability (5%), with respect to threshold-based methodologies and FCM. The repeatability provided by all segmentation algorithms considered was very high with a negligible variability of <5% in comparison to that associated with manual delineation (5-35%). The use of advanced image segmentation algorithms may not only allow high accuracy as previously demonstrated, but also provide a robust and repeatable tool to aid physicians as an initial guess in determining functional volumes in PET. (orig.)

  12. Smectite alteration

    International Nuclear Information System (INIS)

    Anderson, D.M.

    1984-11-01

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  13. Internal and external validation of an ESTRO delineation guideline

    DEFF Research Database (Denmark)

    Eldesoky, Ahmed R.; Yates, Esben Svitzer; Nyeng, Tine B

    2016-01-01

    Background and purpose To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. Materials and methods Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized...... and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. Conclusions ABAS is a clinically useful tool for segmenting structures in breast cancer loco...

  14. LMFBR accident delineation study: approach and preliminary results

    International Nuclear Information System (INIS)

    Williams, D.C.; Sholtis, J.A.; Rios, M.; Worledge, D.H.; Conrad, P.W.; Varela, D.W.; Pickard, P.S.

    1979-01-01

    Event trees have been constructed for all phases of LMFBR accidents. The trees proved useful for identifying meaningful initiating accident categories and containment responses. In these areas, quantification appears feasible, given an adequate data base. Event trees were also used to represent in-core phenomenological questions governing accident progression and energetics, but here quantification appears impracticable because pervasive phenomenological uncertainties exist. Infrequent accident initiation is the dominant factor in assuring low risk. Nevertheless, containment promises an additional measure of risk reduction provided severe energetics are highly unlikely. The delineation served to systematize LMFBR safety issues and should aid in evaluating LMFBR R and D priorities

  15. Validation of holistic nursing competencies: role-delineation study, 2012.

    Science.gov (United States)

    Erickson, Helen Lorraine; Erickson, Margaret Elizabeth; Campbell, Joan A; Brekke, Mary E; Sandor, M Kay

    2013-12-01

    The American Holistic Nurses Credentialing Corporation (AHNCC), certifying body for nurses practicing within the precepts of holistic nursing, uses a systematic process to guide program development. A previous publication described their early work that distinguished basic and advanced holistic nursing and development of related examinations. A more recent publication described the work of AHNCC from 2004 to 2012, including a role-delineation study (RDS) that was undertaken to identify and validate competencies currently used by holistic nurses. A final report describes the RDS design, methods, and raw data information. This article discusses AHNCC's goals for undertaking the 2012 Holistic Nursing RDS and the implications for the certification programs.

  16. Delineating the Impact of Weightlessness on Human Physiology Using Computational Models

    Science.gov (United States)

    Kassemi, Mohammad

    2015-01-01

    Microgravity environment has profound effects on several important human physiological systems. The impact of weightlessness is usually indirect as mediated by changes in the biological fluid flow and transport and alterations in the deformation and stress fields of the compliant tissues. In this context, Fluid-Structural and Fluid-Solid Interaction models provide a valuable tool in delineating the physical origins of the physiological changes so that systematic countermeasures can be devised to reduce their adverse effects. In this presentation, impact of gravity on three human physiological systems will be considered. The first case involves prediction of cardiac shape change and altered stress distributions in weightlessness. The second, presents a fluid-structural-interaction (FSI) analysis and assessment of the vestibular system and explores the reasons behind the unexpected microgravity caloric stimulation test results performed aboard the Skylab. The last case investigates renal stone development in microgravity and the possible impact of re-entry into partial gravity on the development and transport of nucleating, growing, and agglomerating renal calculi in the nephron. Finally, the need for model validation and verification and application of the FSI models to assess the effects of Artificial Gravity (AG) are also briefly discussed.

  17. Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

    Science.gov (United States)

    Ciumas, Carolina; Lindström, Per; Aoun, Bernard; Savic, Ivanka

    2008-01-15

    Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

  18. Automatic tumour volume delineation in respiratory-gated PET images

    International Nuclear Information System (INIS)

    Gubbi, Jayavardhana; Palaniswami, Marimuthu; Kanakatte, Aparna; Mani, Nallasamy; Kron, Tomas; Binns, David; Srinivasan, Bala

    2011-01-01

    Positron emission tomography (PET) is a state-of-the-art functional imaging technique used in the accurate detection of cancer. The main problem with the tumours present in the lungs is that they are non-stationary during each respiratory cycle. Tumours in the lungs can get displaced up to 2.5 cm during respiration. Accurate detection of the tumour enables avoiding the addition of extra margin around the tumour that is usually used during radiotherapy treatment planning. This paper presents a novel method to detect and track tumour in respiratory-gated PET images. The approach followed to achieve this task is to automatically delineate the tumour from the first frame using support vector machines. The resulting volume and position information from the first frame is used in tracking its motion in the subsequent frames with the help of level set (LS) deformable model. An excellent accuracy of 97% is obtained using wavelets and support vector machines. The volume calculated as a result of the machine learning (ML) stage is used as a constraint for deformable models and the tumour is tracked in the remaining seven phases of the respiratory cycle. As a result, the complete information about tumour movement during each respiratory cycle is available in relatively short time. The combination of the LS and ML approach accurately delineated the tumour volume from all frames, thereby providing a scope of using PET images towards planning an accurate and effective radiotherapy treatment for lung cancer.

  19. Delineating Biophysical Environments of the Sunda Banda Seascape, Indonesia

    Directory of Open Access Journals (Sweden)

    Mingshu Wang

    2015-01-01

    Full Text Available The Sunda Banda Seascape (SBS, located in the center of the Coral Triangle, is a global center of marine biodiversity and a conservation priority. We proposed the first biophysical environmental delineation of the SBS using globally available satellite remote sensing and model-assimilated data to categorize this area into unique and meaningful biophysical classes. Specifically, the SBS was partitioned into eight biophysical classes characterized by similar sea surface temperature, chlorophyll a concentration, currents, and salinity patterns. Areas within each class were expected to have similar habitat types and ecosystem functions. Our work supplemented prevailing global marine management schemes by focusing in on a regional scale with finer spatial resolution. It also provided a baseline for academic research, ecological assessments and will facilitate marine spatial planning and conservation activities in the area. In addition, the framework and methods of delineating biophysical environments we presented can be expanded throughout the whole Coral Triangle to support research and conservation activities in this important region.

  20. Target delineation in radiosurgery for cerebral arteriovenous malformations

    International Nuclear Information System (INIS)

    Guo, W.Y.; Nordell, B.; Karlsson, B.; Soederman, M.; Lindqvist, M.; Ericson, K.; Franck, A.; Lax, I.; Lindquist, C.

    1993-01-01

    A study of 6 selected arteriovenous malformation (AVM) patients was performed to investigate the feasibility of delineating an AVM on MR images and to compare the AVM volume outlined on different images. Conventional stereotaxic angiograms, stereotaxic MR images and MR angiograms using several different pulse sequences were obtained prior to radiosurgery. Treatment plans were made from the conventional stereotaxic angiograms. These plans were then transferred to a separate dose planning computer which displayed the MR images with the superimposed isodose lines. The radiated volumes of AVM and brain tissue were measured from these MR images. Last, an assessment was made of the radiation volume needed for an appropriate treatment of the AVM if the treatment plan was made from the MR images rather than from the conventional stereotaxic angiogram. It was possible to delineate medium and large size AVM nidi on stereotaxic MR images based on an integration of information obtained from various pulse sequences. The estimated volumes of the AVM nidi were found to be larger on the conventional stereotaxic angiograms than on the stereotaxic MR images. Consequently, a dose plan based on a conventional stereotaxic angiogram would result in a higher integral dose to the brain with the same target dose. By using reliable MR information it is expected that the volume of brain exposed to radiation could be decreased and the adverse effects of stereotactic radiosurgery for AVM thereby minimized. (orig.)

  1. Optical system for object detection and delineation in space

    Science.gov (United States)

    Handelman, Amir; Shwartz, Shoam; Donitza, Liad; Chaplanov, Loran

    2018-01-01

    Object recognition and delineation is an important task in many environments, such as in crime scenes and operating rooms. Marking evidence or surgical tools and attracting the attention of the surrounding staff to the marked objects can affect people's lives. We present an optical system comprising a camera, computer, and small laser projector that can detect and delineate objects in the environment. To prove the optical system's concept, we show that it can operate in a hypothetical crime scene in which a pistol is present and automatically recognize and segment it by various computer-vision algorithms. Based on such segmentation, the laser projector illuminates the actual boundaries of the pistol and thus allows the persons in the scene to comfortably locate and measure the pistol without holding any intermediator device, such as an augmented reality handheld device, glasses, or screens. Using additional optical devices, such as diffraction grating and a cylinder lens, the pistol size can be estimated. The exact location of the pistol in space remains static, even after its removal. Our optical system can be fixed or dynamically moved, making it suitable for various applications that require marking of objects in space.

  2. Recommendations for the delineation of organs at risk in ENT radiotherapy; Recommandations de delineation des organes a risque en radiotherapie ORL

    Energy Technology Data Exchange (ETDEWEB)

    Ali, D.; Halimi, P.; Berges, O.; Deberne, M.; Botti, M.; Giraud, P. [Hopital europeen Georges-Pompidou, Paris (France); Servagi-Vernat, S. [CHUjean-Minjoz, Besancon (France)

    2011-10-15

    Based on a literature survey, the authors propose recommendations for the delineation of the pharyngeal constrictor muscles, inner ear, larynx, buccal cavity, and temporomandibular joint. These recommendations of delineation of organs at risk are related to the functional anatomy of the considered structures, and correspond to volumes used in published surveys on dose-volume toxicity. They are simple and reproducible. Short communication

  3. Development, cross-species/genera transferability of novel EST-SSR markers and their utility in revealing population structure and genetic diversity in sugarcane

    KAUST Repository

    Singh, Ram K.; Jena, Satya N.; Khan, Mohammad Suhail; Yadav, Sonia; Banarjee, Nandita; Raghuvanshi, Saurabh; Bhardwaj, Vasudha; Dattamajumder, Sanjay K.; Kapur, Raman; Solomon, Sushil; Swapna, M.; Srivastava, Sangeeta; Tyagi, Akhilesh K.

    2013-01-01

    for population structure using model-based approach, seven genetically distinct groups or admixtures thereof were observed in sugarcane. Results of principal coordinate analysis or UPGMA to evaluate genetic relationships delineated also the 124 accessions

  4. Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic Clades in the Lion (Panthera leo)

    NARCIS (Netherlands)

    Bertola, L.D.; Jongbloed, H.; van der Gaag, K.J.; de Knijff, P.; Yamaguchi, N.; Hooghiemstra, H.; Bauer, H.; Henschel, P.; White, P.A.; Driscoll, C.A.; Tende, T.; Ottosson, U.; Saidu, Y.; Vrieling, K.; de Iongh, H.H.

    2016-01-01

    Comparative phylogeography of African savannah mammals shows a congruent pattern in which populations in West/Central Africa are distinct from populations in East/Southern Africa. However, for the lion, all African populations are currently classified as a single subspecies (Panthera leo leo), while

  5. Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

    NARCIS (Netherlands)

    Huard, Richard C; Fabre, Michel; Haas, Petra de; Lazzarini, Luiz Claudio Oliveira; Soolingen, Dick van; Cousins, Debby; Ho, John L

    2006-01-01

    In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol.

  6. A probabilistic approach to delineating functional brain regions

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Svarer, Claus; Frokjaer, Vibe G

    2009-01-01

    The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphe nuclei, a collection of nuclei situated in the brain stem known...... to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphe nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10...... healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared...

  7. Delineation of geological facies from poorly differentiated data

    Energy Technology Data Exchange (ETDEWEB)

    Wohlberg, Brendt [Los Alamos National Laboratory; Tartakovsky, Daniel [UCSC

    2008-01-01

    The ability to delineate geologic facies and to estima.te their properties from sparse data is essential for modeling physical and biochemical processes occurring in the 'ubsurface. If such data are poorly differentiated, this challcnrring task is complicated further by the absence of a clear distinction between different hydrofacies even at locations where data. are available. vVe consider three alt mative approaches for analysis of poorly differentiated data: a k-means clU!:iterinrr algorithm, an expectation-maximization algorithm, and a minimum-variance algorithm. Two distinct synthetically generated geological settings are used to r:tnalyze the ability of these algorithmti to as ign accurately the membership of such data in a given geologic facies. On average, the minimum-variance algorithm provides a more robust p rformance than its two counterparts and when combined with a nearest-neighbor algorithm, it also yields the most accurate reconstruction of the boundaries between the facies.

  8. ORIGAMI: DELINEATING HALOS USING PHASE-SPACE FOLDS

    Energy Technology Data Exchange (ETDEWEB)

    Falck, Bridget L.; Neyrinck, Mark C.; Szalay, Alexander S. [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States)

    2012-08-01

    We present the ORIGAMI method of identifying structures, particularly halos, in cosmological N-body simulations. Structure formation can be thought of as the folding of an initially flat three-dimensional manifold in six-dimensional phase space. ORIGAMI finds the outer folds that delineate these structures. Halo particles are identified as those that have undergone shell-crossing along three orthogonal axes, providing a dynamical definition of halo regions that is independent of density. ORIGAMI also identifies other morphological structures: particles that have undergone shell-crossing along 2, 1, or 0 orthogonal axes correspond to filaments, walls, and voids, respectively. We compare this method to a standard friends-of-friends halo-finding algorithm and find that ORIGAMI halos are somewhat larger, more diffuse, and less spherical, though the global properties of ORIGAMI halos are in good agreement with other modern halo-finding algorithms.

  9. ORIGAMI: DELINEATING HALOS USING PHASE-SPACE FOLDS

    International Nuclear Information System (INIS)

    Falck, Bridget L.; Neyrinck, Mark C.; Szalay, Alexander S.

    2012-01-01

    We present the ORIGAMI method of identifying structures, particularly halos, in cosmological N-body simulations. Structure formation can be thought of as the folding of an initially flat three-dimensional manifold in six-dimensional phase space. ORIGAMI finds the outer folds that delineate these structures. Halo particles are identified as those that have undergone shell-crossing along three orthogonal axes, providing a dynamical definition of halo regions that is independent of density. ORIGAMI also identifies other morphological structures: particles that have undergone shell-crossing along 2, 1, or 0 orthogonal axes correspond to filaments, walls, and voids, respectively. We compare this method to a standard friends-of-friends halo-finding algorithm and find that ORIGAMI halos are somewhat larger, more diffuse, and less spherical, though the global properties of ORIGAMI halos are in good agreement with other modern halo-finding algorithms.

  10. Delineation of groundwater potential zone: An AHP/ANP approach

    Indian Academy of Sciences (India)

    Groundwater; multi-criteria decision making; analytical network process. J. Earth Syst. ... than AHP for decision making. ... the themes and provide utility weights for the alter- natives ... theory that has been applied to classifying ETM+ image.

  11. Electrocardiogram ST-Segment Morphology Delineation Method Using Orthogonal Transformations.

    Directory of Open Access Journals (Sweden)

    Miha Amon

    Full Text Available Differentiation between ischaemic and non-ischaemic transient ST segment events of long term ambulatory electrocardiograms is a persisting weakness in present ischaemia detection systems. Traditional ST segment level measuring is not a sufficiently precise technique due to the single point of measurement and severe noise which is often present. We developed a robust noise resistant orthogonal-transformation based delineation method, which allows tracing the shape of transient ST segment morphology changes from the entire ST segment in terms of diagnostic and morphologic feature-vector time series, and also allows further analysis. For these purposes, we developed a new Legendre Polynomials based Transformation (LPT of ST segment. Its basis functions have similar shapes to typical transient changes of ST segment morphology categories during myocardial ischaemia (level, slope and scooping, thus providing direct insight into the types of time domain morphology changes through the LPT feature-vector space. We also generated new Karhunen and Lo ève Transformation (KLT ST segment basis functions using a robust covariance matrix constructed from the ST segment pattern vectors derived from the Long Term ST Database (LTST DB. As for the delineation of significant transient ischaemic and non-ischaemic ST segment episodes, we present a study on the representation of transient ST segment morphology categories, and an evaluation study on the classification power of the KLT- and LPT-based feature vectors to classify between ischaemic and non-ischaemic ST segment episodes of the LTST DB. Classification accuracy using the KLT and LPT feature vectors was 90% and 82%, respectively, when using the k-Nearest Neighbors (k = 3 classifier and 10-fold cross-validation. New sets of feature-vector time series for both transformations were derived for the records of the LTST DB which is freely available on the PhysioNet website and were contributed to the LTST DB. The

  12. The Significance of Land Cover Delineation on Soil Erosion Assessment.

    Science.gov (United States)

    Efthimiou, Nikolaos; Psomiadis, Emmanouil

    2018-04-25

    The study aims to evaluate the significance of land cover delineation on soil erosion assessment. To that end, RUSLE (Revised Universal Soil Loss Equation) was implemented at the Upper Acheloos River catchment, Western Central Greece, annually and multi-annually for the period 1965-92. The model estimates soil erosion as the linear product of six factors (R, K, LS, C, and P) considering the catchment's climatic, pedological, topographic, land cover, and anthropogenic characteristics, respectively. The C factor was estimated using six alternative land use delineations of different resolution, namely the CORINE Land Cover (CLC) project (2000, 2012 versions) (1:100,000), a land use map conducted by the Greek National Agricultural Research Foundation (NAGREF) (1:20,000), a land use map conducted by the Greek Payment and Control Agency for Guidance and Guarantee Community Aid (PCAGGCA) (1:5,000), and the Landsat 8 16-day Normalized Difference Vegetation Index (NDVI) dataset (30 m/pixel) (two approximations) based on remote sensing data (satellite image acquired on 07/09/2016) (1:40,000). Since all other factors remain unchanged per each RUSLE application, the differences among the yielded results are attributed to the C factor (thus the land cover pattern) variations. Validation was made considering the convergence between simulated (modeled) and observed sediment yield. The latter was estimated based on field measurements conducted by the Greek PPC (Public Power Corporation). The model performed best at both time scales using the Landsat 8 (Eq. 13) dataset, characterized by a detailed resolution and a satisfactory categorization, allowing the identification of the most susceptible to erosion areas.

  13. [Epigenetic alterations in acute lymphoblastic leukemia].

    Science.gov (United States)

    Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  14. Quality assurance tool for organ at risk delineation in radiation therapy using a parametric statistical approach.

    Science.gov (United States)

    Hui, Cheukkai B; Nourzadeh, Hamidreza; Watkins, William T; Trifiletti, Daniel M; Alonso, Clayton E; Dutta, Sunil W; Siebers, Jeffrey V

    2018-02-26

    To develop a quality assurance (QA) tool that identifies inaccurate organ at risk (OAR) delineations. The QA tool computed volumetric features from prior OAR delineation data from 73 thoracic patients to construct a reference database. All volumetric features of the OAR delineation are computed in three-dimensional space. Volumetric features of a new OAR are compared with respect to those in the reference database to discern delineation outliers. A multicriteria outlier detection system warns users of specific delineation outliers based on combinations of deviant features. Fifteen independent experimental sets including automatic, propagated, and clinically approved manual delineation sets were used for verification. The verification OARs included manipulations to mimic common errors. Three experts reviewed the experimental sets to identify and classify errors, first without; and then 1 week after with the QA tool. In the cohort of manual delineations with manual manipulations, the QA tool detected 94% of the mimicked errors. Overall, it detected 37% of the minor and 85% of the major errors. The QA tool improved reviewer error detection sensitivity from 61% to 68% for minor errors (P = 0.17), and from 78% to 87% for major errors (P = 0.02). The QA tool assists users to detect potential delineation errors. QA tool integration into clinical procedures may reduce the frequency of inaccurate OAR delineation, and potentially improve safety and quality of radiation treatment planning. © 2018 American Association of Physicists in Medicine.

  15. Semi-automatic delineation using weighted CT-MRI registered images for radiotherapy of nasopharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fitton, I. [European Georges Pompidou Hospital, Department of Radiology, 20 rue Leblanc, 75015, Paris (France); Cornelissen, S. A. P. [Image Sciences Institute, UMC, Department of Radiology, P.O. Box 85500, 3508 GA Utrecht (Netherlands); Duppen, J. C.; Rasch, C. R. N.; Herk, M. van [The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiotherapy, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Steenbakkers, R. J. H. M. [University Medical Center Groningen, Department of Radiation Oncology, Hanzeplein 1, 9713 GZ Groningen (Netherlands); Peeters, S. T. H. [UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgique (Belgium); Hoebers, F. J. P. [Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO clinic), GROW School for Oncology and Development Biology Maastricht, 6229 ET Maastricht (Netherlands); Kaanders, J. H. A. M. [UMC St-Radboud, Department of Radiotherapy, Geert Grooteplein 32, 6525 GA Nijmegen (Netherlands); Nowak, P. J. C. M. [ERASMUS University Medical Center, Department of Radiation Oncology,Groene Hilledijk 301, 3075 EA Rotterdam (Netherlands)

    2011-08-15

    Purpose: To develop a delineation tool that refines physician-drawn contours of the gross tumor volume (GTV) in nasopharynx cancer, using combined pixel value information from x-ray computed tomography (CT) and magnetic resonance imaging (MRI) during delineation. Methods: Operator-guided delineation assisted by a so-called ''snake'' algorithm was applied on weighted CT-MRI registered images. The physician delineates a rough tumor contour that is continuously adjusted by the snake algorithm using the underlying image characteristics. The algorithm was evaluated on five nasopharyngeal cancer patients. Different linear weightings CT and MRI were tested as input for the snake algorithm and compared according to contrast and tumor to noise ratio (TNR). The semi-automatic delineation was compared with manual contouring by seven experienced radiation oncologists. Results: A good compromise for TNR and contrast was obtained by weighing CT twice as strong as MRI. The new algorithm did not notably reduce interobserver variability, it did however, reduce the average delineation time by 6 min per case. Conclusions: The authors developed a user-driven tool for delineation and correction based a snake algorithm and registered weighted CT image and MRI. The algorithm adds morphological information from CT during the delineation on MRI and accelerates the delineation task.

  16. GSD Update: Ushering in a new age of genetics to restore lands and conserve species

    Science.gov (United States)

    Deborah M. Finch

    2013-01-01

    Plant genetic information provides critical knowledge necessary to mitigate the impacts of climate change through ecological restoration. The first step in restoration is recognizing and delineating genetic boundaries at different taxonomic and spatial hierarchies (e.g., species, subspecies and populations). The second step is an assessment of the genetic diversity...

  17. Delineating social network data anonymization via random edge perturbation

    KAUST Repository

    Xue, Mingqiang

    2012-01-01

    Social network data analysis raises concerns about the privacy of related entities or individuals. To address this issue, organizations can publish data after simply replacing the identities of individuals with pseudonyms, leaving the overall structure of the social network unchanged. However, it has been shown that attacks based on structural identification (e.g., a walk-based attack) enable an adversary to re-identify selected individuals in an anonymized network. In this paper we explore the capacity of techniques based on random edge perturbation to thwart such attacks. We theoretically establish that any kind of structural identification attack can effectively be prevented using random edge perturbation and show that, surprisingly, important properties of the whole network, as well as of subgraphs thereof, can be accurately calculated and hence data analysis tasks performed on the perturbed data, given that the legitimate data recipient knows the perturbation probability as well. Yet we also examine ways to enhance the walk-based attack, proposing a variant we call probabilistic attack. Nevertheless, we demonstrate that such probabilistic attacks can also be prevented under sufficient perturbation. Eventually, we conduct a thorough theoretical study of the probability of success of any}structural attack as a function of the perturbation probability. Our analysis provides a powerful tool for delineating the identification risk of perturbed social network data; our extensive experiments with synthetic and real datasets confirm our expectations. © 2012 ACM.

  18. Volcanic calderas delineate biogeographic provinces among Yellowstone thermophiles.

    Science.gov (United States)

    Takacs-Vesbach, Cristina; Mitchell, Kendra; Jackson-Weaver, Olan; Reysenbach, Anna-Louise

    2008-07-01

    It has been suggested that the distribution of microorganisms should be cosmopolitan because of their enormous capacity for dispersal. However, recent studies have revealed that geographically isolated microbial populations do exist. Geographic distance as a barrier to dispersal is most often invoked to explain these distributions. Here we show that unique and diverse sequences of the bacterial genus Sulfurihydrogenibium exist in Yellowstone thermal springs, indicating that these sites are geographically isolated. Although there was no correlation with geographic distance or the associated geochemistry of the springs, there was a strong historical signal. We found that the Yellowstone calderas, remnants of prehistoric volcanic eruptions, delineate biogeographical provinces for the Sulfurihydrogenibium within Yellowstone (chi(2): 9.7, P = 0.002). The pattern of distribution that we have detected suggests that major geological events in the past 2 million years explain more of the variation in sequence diversity in this system than do contemporary factors such as habitat or geographic distance. These findings highlight the importance of historical legacies in determining contemporary microbial distributions and suggest that the same factors that determine the biogeography of macroorganisms are also evident among bacteria.

  19. In-situ hydrocarbon delineation using laser-induced fluorescence

    International Nuclear Information System (INIS)

    Taer, A.D.; Hastings, R.W.; Brown, A.Y.; Frend, R.

    1996-01-01

    An investigation of hydrocarbons in soils was conducted at an active Shell Oil Company petroleum products terminal, located in Carson, California. An investigation approach involving Laser-Induced Fluorescence (LIF) and Cone Penetrometer Testing (CPT) technologies was implemented to provide real-time, in-situ characterization of site stratigraphy, hydrocarbon distribution and importantly, hydrocarbon product differentiation. The area of investigation is located along a property boundary, where a plume of separate phase hydrocarbons has been actively recovered for several years. CPT/LIF technology was selected for the investigation since previous delineation efforts using hydrocarbon fingerprinting methods proved inconclusive. Additionally, the CPT/LIF technology had the potential to provide a cost effective solution to accomplish project objectives. Based on the information obtained during this investigation, it was determined that the plume of separate phase hydrocarbons along the northern property boundary is from a source distinctly different than any identified hydrocarbons known to be from on-site sources. In addition, the plume was determined to not be connected with any other known on-site hydrocarbon plumes. The results of this CPT/LIF investigation were consistent with the known hydrogeologic conditions. This evaluation determined that CPT/LIF technology was very effective in addressing project objectives and resulted in a significant cost savings

  20. Delineation of the normal esophagus at computed tomography

    International Nuclear Information System (INIS)

    Samuelsson, L.; Tylen, U.; Sahlgrenska Sjukhuset, Goeteborg

    1985-01-01

    It has been accepted by many that the esophagus in its entire length is easy to delineate at CT in most patients due to surrounding fat planes. As this is not the experience of the present authors, the CT of the thorax in 100 normal men and women without mediastinal disease and in good nutritional status was reviewed, to record the relationship between the esophagus and neighbouring structures. In the upper third of the esophagus there is almost never a definite border between its wall and that of the trachea, while a separating border or even a fat plane can be seen to the spine in between 25 and 50 per cent of those tested. The vessels, as a rule, have a flat plane towards the esophagus. The middle part of the esophagus has the same intimate relationship to the trachea and left main bronchus, i.e. almost never any separating border. Two thirds of the cases have no border to the upper part of the pericardium (left atrium), while about 70 per cent have a border or fat plane towards the aorta. The middle and lower third of the esophagus has, as a rule, a distinct border or fat plane to the spine. In about 50 per cent of the patients the anterior wall of the lower esophagus is separable from the pericardium. (orig.)

  1. Compact-Morphology-based poly-metallic Nodule Delineation.

    Science.gov (United States)

    Schoening, Timm; Jones, Daniel O B; Greinert, Jens

    2017-10-17

    Poly-metallic nodules are a marine resource considered for deep sea mining. Assessing nodule abundance is of interest for mining companies and to monitor potential environmental impact. Optical seafloor imaging allows quantifying poly-metallic nodule abundance at spatial scales from centimetres to square kilometres. Towed cameras and diving robots acquire high-resolution imagery that allow detecting individual nodules and measure their sizes. Spatial abundance statistics can be computed from these size measurements, providing e.g. seafloor coverage in percent and the nodule size distribution. Detecting nodules requires segmentation of nodule pixels from pixels showing sediment background. Semi-supervised pattern recognition has been proposed to automate this task. Existing nodule segmentation algorithms employ machine learning that trains a classifier to segment the nodules in a high-dimensional feature space. Here, a rapid nodule segmentation algorithm is presented. It omits computation-intense feature-based classification and employs image processing only. It exploits a nodule compactness heuristic to delineate individual nodules. Complex machine learning methods are avoided to keep the algorithm simple and fast. The algorithm has successfully been applied to different image datasets. These data sets were acquired by different cameras, camera platforms and in varying illumination conditions. Their successful analysis shows the broad applicability of the proposed method.

  2. Permafrost delineation for remediation planning : Fort Wainwright, Alaska

    Energy Technology Data Exchange (ETDEWEB)

    Astley, B. [Cold Regions Research and Engineering Laboratory, Anchorage, AK (United States); Snyder, C. [YEC Inc., Valley Cottage, NJ (United States); Delaney, A. [Cold Regions Research and Engineering Laboratory, Fairbanks, AK (United States); Arcone, S.; Lawson, D. [Cold Regions Research and Engineering Laboratory, Hanover, NH (United States)

    2003-07-01

    In the summer of 1999, geophysical and hydrogeological surveys were conducted at the Birch Hill Tank Farm and Truck Fill Stand in Fort Wainwright, Alaska to assess the distribution of benzene, 1,2-dichloroethane, and 1,2-dibromoethane. The Birch Hill site consists of a silt, sand and gravel fluvial deposit that overlies bedrock. Permafrost occurs discontinuously throughout the alluvium and underlying bedrock, resulting in a complex aquifer distribution. The bedrock beneath the Tank Farm is highly fractured and faulted with a weathered horizon that is 30 meters thick. The goal of this study was to map the discontinuous permafrost and aquifers in the alluvial deposits and weathered bedrock zone for the purpose of delineating bedrock depth and structural features that influence ground water flow. Several methods were used to define subsurface conditions, including borehole logs, DC resistivity, and ground-penetrating radar. A 3-D hydrogeologic model was used to develop a ground water flow model used to determine contaminant migration pathways and rates. The permafrost configuration was found to be the most important boundary condition in this model. 7 refs., 1 tab., 5 figs.

  3. Directional phytoscreening: contaminant gradients in trees for plume delineation.

    Science.gov (United States)

    Limmer, Matt A; Shetty, Mikhil K; Markus, Samantha; Kroeker, Ryan; Parker, Beth L; Martinez, Camilo; Burken, Joel G

    2013-08-20

    Tree sampling methods have been used in phytoscreening applications to delineate contaminated soil and groundwater, augmenting traditional investigative methods that are time-consuming, resource-intensive, invasive, and costly. In the past decade, contaminant concentrations in tree tissues have been shown to reflect the extent and intensity of subsurface contamination. This paper investigates a new phytoscreening tool: directional tree coring, a concept originating from field data that indicated azimuthal concentrations in tree trunks reflected the concentration gradients in the groundwater around the tree. To experimentally test this hypothesis, large diameter trees were subjected to subsurface contaminant concentration gradients in a greenhouse study. These trees were then analyzed for azimuthal concentration gradients in aboveground tree tissues, revealing contaminant centroids located on the side of the tree nearest the most contaminated groundwater. Tree coring at three field sites revealed sufficiently steep contaminant gradients in trees reflected nearby groundwater contaminant gradients. In practice, trees possessing steep contaminant gradients are indicators of steep subsurface contaminant gradients, providing compass-like information about the contaminant gradient, pointing investigators toward higher concentration regions of the plume.

  4. Oncology Nurse Navigation: Results of the 2016 Role Delineation Study.

    Science.gov (United States)

    Lubejko, Barbara G; Bellfield, Sonia; Kahn, Elisa; Lee, Carrie; Peterson, Nicole; Rose, Traudi; Murphy, Cynthia Miller; McCorkle, Michele

    2017-02-01

    In 2011, an oncology nurse navigator (ONN) role delineation survey (RDS) was conducted by the Oncology Nursing Society (ONS) when the role was relatively new to oncology. Results did not demonstrate a unique skill set for the ONN; however, since then, the role has expanded. ONS and the Oncology Nursing Certification Corporation partnered in 2016 to complete an RDS of ONNs to redefine the role and determine the need for an ONN certification examination. A structured RDS was conducted using a formal consensus-building process. A survey was developed and released to examine the specific tasks, knowledge, and skills for the ONN as well as to determine which role possesses more responsibility for the tasks. The ONN role is evolving, and more was learned about its key tasks, including differences in the responsibilities of the ONN and the clinical or staff nurse. However, the RDS did not find an adequate difference in the knowledge required by the ONN and the clinical or staff nurse to support the need for a separate ONN certification.

  5. Reverse time migration of prism waves for salt flank delineation

    KAUST Repository

    Dai, Wei; Schuster, Gerard T.

    2013-01-01

    In this paper, we present a new reverse time migration method for imaging salt flanks with prism wave reflections. It consists of four steps: (1) migrating the seismic data with conventional RTM to give the RTM image; (2) using the RTM image as a reflectivity model to simulate source-side reflections with the Born approximation; (3) zero-lag correlation of the source-side reflection wavefields and receiver-side wavefields to produce the prism wave migration image; and (4) repeating steps 2 and 3 for the receiver-side reflections. An advantage of this method is that there is no need to pick the horizontal reflectors prior to migration of the prism waves. It also separately images the vertical structures at a different step to reduce crosstalk interference. The disadvantage of prism wave migration algorithm is that its computational cost is twice that of conventional RTM. The empirical results with a salt model suggest that prism wave migration can be an effective method for salt flank delineation in the absence of diving waves.

  6. Reverse time migration of prism waves for salt flank delineation

    KAUST Repository

    Dai, Wei

    2013-09-22

    In this paper, we present a new reverse time migration method for imaging salt flanks with prism wave reflections. It consists of four steps: (1) migrating the seismic data with conventional RTM to give the RTM image; (2) using the RTM image as a reflectivity model to simulate source-side reflections with the Born approximation; (3) zero-lag correlation of the source-side reflection wavefields and receiver-side wavefields to produce the prism wave migration image; and (4) repeating steps 2 and 3 for the receiver-side reflections. An advantage of this method is that there is no need to pick the horizontal reflectors prior to migration of the prism waves. It also separately images the vertical structures at a different step to reduce crosstalk interference. The disadvantage of prism wave migration algorithm is that its computational cost is twice that of conventional RTM. The empirical results with a salt model suggest that prism wave migration can be an effective method for salt flank delineation in the absence of diving waves.

  7. Recommendations for the delineation of organs at risk in ENT radiotherapy

    International Nuclear Information System (INIS)

    Ali, D.; Halimi, P.; Berges, O.; Deberne, M.; Botti, M.; Giraud, P.; Servagi-Vernat, S.

    2011-01-01

    Based on a literature survey, the authors propose recommendations for the delineation of the pharyngeal constrictor muscles, inner ear, larynx, buccal cavity, and temporomandibular joint. These recommendations of delineation of organs at risk are related to the functional anatomy of the considered structures, and correspond to volumes used in published surveys on dose-volume toxicity. They are simple and reproducible. Short communication

  8. The 14 bp Del/Ins HLA-G Polymorphism Is Related with High Blood Pressure in Acute Coronary Syndrome and Type 2 Diabetes Mellitus

    Science.gov (United States)

    García-González, Ilian Janet; Valle, Yeminia; Rivas, Fernando; Figuera-Villanueva, Luis Eduardo; Muñoz-Valle, José Francisco; Flores-Salinas, Hector Enrique; Gutiérrez-Amavizca, Bianca Ethel; Dávalos-Rodríguez, Nory Omayra; Padilla-Gutiérrez, Jorge Ramón

    2014-01-01

    Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (ORc = 1.65, P = 0.02). The genetic recessive model showed similar findings (ORc = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups. PMID:24689061

  9. Sequential Versus Simultaneous Market Delineation: The Relevant Antitrust Market for Salmon

    DEFF Research Database (Denmark)

    Haldrup, Niels; Peter, Møllgaard

    Delineation of the relevant market forms a pivotal part of most antitrust cases. The standard approach is sequential. First the product market is delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographical dimension will no...... and geographical markets. Using a unique data set for prices of Norwegian and Scottish salmon, we propose a methodology for simultaneous market delineation and we demonstrate that compared to a sequential approach conclusions will be reversed.......Delineation of the relevant market forms a pivotal part of most antitrust cases. The standard approach is sequential. First the product market is delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographical dimension...

  10. A segmentation approach for a delineation of terrestrial ecoregions

    Science.gov (United States)

    Nowosad, J.; Stepinski, T.

    2017-12-01

    Terrestrial ecoregions are the result of regionalization of land into homogeneous units of similar ecological and physiographic features. Terrestrial Ecoregions of the World (TEW) is a commonly used global ecoregionalization based on expert knowledge and in situ observations. Ecological Land Units (ELUs) is a global classification of 250 meters-sized cells into 4000 types on the basis of the categorical values of four environmental variables. ELUs are automatically calculated and reproducible but they are not a regionalization which makes them impractical for GIS-based spatial analysis and for comparison with TEW. We have regionalized terrestrial ecosystems on the basis of patterns of the same variables (land cover, soils, landform, and bioclimate) previously used in ELUs. Considering patterns of categorical variables makes segmentation and thus regionalization possible. Original raster datasets of the four variables are first transformed into regular grids of square-sized blocks of their cells called eco-sites. Eco-sites are elementary land units containing local patterns of physiographic characteristics and thus assumed to contain a single ecosystem. Next, eco-sites are locally aggregated using a procedure analogous to image segmentation. The procedure optimizes pattern homogeneity of all four environmental variables within each segment. The result is a regionalization of the landmass into land units characterized by uniform pattern of land cover, soils, landforms, climate, and, by inference, by uniform ecosystem. Because several disjoined segments may have very similar characteristics, we cluster the segments to obtain a smaller set of segment types which we identify with ecoregions. Our approach is automatic, reproducible, updatable, and customizable. It yields the first automatic delineation of ecoregions on the global scale. In the resulting vector database each ecoregion/segment is described by numerous attributes which make it a valuable GIS resource for

  11. Delineating the cell death mechanisms associated with skin electroporation.

    Science.gov (United States)

    Schultheis, Katherine; Smith, Trevor R F; Kiosses, William B; Kraynyak, Kimberly A; Wong, Amelia; Oh, Janet; Broderick, Kate Elizabeth

    2018-06-28

    The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of pDNA into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses. Here, we have investigated the possible mechanisms associated with this adjuvant effect, primarily focusing on the cell death pathways associated with the skin EP procedure independent of pDNA delivery. Using the minimally invasive CELLECTRA®-3P intradermal electroporation device that penetrates the epidermal and dermal layers of the skin, we have investigated apoptotic and necrotic cell death in relation to the vicinity of the electrode needles and electric field generated. Employing the well-established TUNEL assay, we detected apoptosis beginning as early as one hour after EP and peaking at the 4 hour time point. The majority of the apoptotic events were detected in the epidermal region directly adjacent to the electrode needle. Using a novel propidium iodide in vivo necrotic cell death assay, we detected necrotic events concentrated in the epidermal region adjacent to the electrode. Furthermore, we detected up-regulation of calreticulin expression on skin cells after EP, thus labeling these cells for uptake by dendritic cells and macrophages. These results allow us to delineate the cell death mechanisms occurring in the skin following intradermal EP independently of pDNA delivery. We believe these events contribute to the adjuvant effect observed following electroporation at the skin treatment site.

  12. Delineation of peatland lagg boundaries from airborne LiDAR

    Science.gov (United States)

    Langlois, Melanie N.; Richardson, Murray C.; Price, Jonathan S.

    2017-09-01

    In Canada, peatlands are the most common type of wetland, but boundary delineation in peatland complexes has received little attention in the scientific literature. Typically, peatland boundaries are mapped as crisp, absolute features, and the transitional lagg zone—the ecotone found between a raised bog and the surrounding mineral land—is often overlooked. In this study, we aim (1) to advance existing approaches for detecting and locating laggs and lagg boundaries using airborne LiDAR surveys and (2) to describe the spatial distribution of laggs around raised bog peatlands. Two contrasting spatial analytical approaches for lagg detection were tested using five LiDAR-derived topographic and vegetation indices: topography, vegetation height, topographic wetness index, the standard deviation of the vegetation's height (as a proxy for the complexity of the vegetation's structure), and local indices of elevation variance. Using a dissimilarity approach (edge-detection, split-moving window analysis), no one variable accurately depicted both the lagg-mineral land and bog-lagg boundaries. Some indicators were better at predicting the bog-lagg boundary (i.e., vegetation height) and others at finding the lagg-mineral land boundary (i.e., topography). Dissimilarity analysis reinforces the usefulness of derived variables (e.g., wetness indices) in locating laggs, especially for those with weak topographic and vegetation gradients. When the lagg was confined between the bog and the adjacent upland, it took a linear form, parallel to the peatland's edge and was easier to predict. When the adjacent mineral land was flat or sloping away from the peatland, the lagg was discontinuous and intermittent and more difficult to predict.

  13. Delineation of the calcineurin-interacting region of cyclophilin B.

    Science.gov (United States)

    Carpentier, M; Allain, F; Haendler, B; Slomianny, M C; Spik, G

    2000-12-01

    The immunosuppressant drug cyclosporin A (CsA) inhibits T-cell function by blocking the phosphatase activity of calcineurin. This effect is mediated by formation of a complex between the drug and cyclophilin (CyP), which creates a composite surface able to make high-affinity contacts with calcineurin. In vitro, the CyPB/CsA complex is more effective in inhibiting calcineurin than the CyPA/CsA and CyPC/CsA complexes, pointing to fine structural differences in the calcineurin-binding region. To delineate the calcineurin-binding region of CyPB, we mutated several amino acids, located in two loops corresponding to CyPA regions known to be involved, as follows: R76A, G77H, D155R, and D158R. Compared to wild-type CyPB, the G77H, D155R, and D158R mutants had intact isomerase and CsA-binding activities, indicating that no major conformational changes had taken place. When complexed to CsA, they all displayed only reduced affinity for calcineurin and much decreased inhibition of calcineurin phosphatase activity. These results strongly suggest that the three amino acids G77, D155, and D158 are directly involved in the interaction of CyPB/CsA with calcineurin, in agreement with their exposed position. The G77, D155, and D158 residues are not maintained in CyPA and might therefore account for the higher affinity of the CyPB/CsA complex for calcineurin.

  14. Delineating advanced practice nursing in New Zealand: a national survey.

    Science.gov (United States)

    Carryer, J; Wilkinson, J; Towers, A; Gardner, G

    2018-03-01

    A variety of advanced practice nursing roles and titles have proliferated in response to the changing demands of a population characterized by increasing age and chronic illness. Whilst similarly identified as advanced practice roles, they do not share a common practice profile, educational requirements or legislative direction. The lack of clarity limits comparative research that can inform policy and health service planning. To identify advanced practice roles within nursing titles employed in New Zealand and practice differences between advanced practice and other roles. Replicating recent Australian research, 3255 registered nurses/nurse practitioners in New Zealand completed the amended Advanced Practice Delineation survey tool. The mean domain scores of the predominant advanced practice position were compared with those of other positions. Differences between groups were explored using one-way ANOVA and post hoc between group comparisons. Four nursing position bands were identified: nurse practitioner, clinical nurse specialist, domain-specific and registered nurse. Significant differences between the bands were found on many domain scores. The nurse practitioner and clinical nurse specialist bands had the most similar practice profiles, nurse practitioners being more involved in direct care and professional leadership. Similar to the position of clinical nurse consultant in Australia, those practicing as clinical nurse specialists were deemed to reflect the threshold for advanced practice nursing. The results identified different practice patterns for the identified bands and distinguish the advanced practice nursing roles. By replicating the Australian study of Gardener et al. (2016), this NZ paper extends the international data available to support more evidence-based nursing workforce planning and policy development. © 2017 International Council of Nurses.

  15. Barcoding against a paradox? Combined molecular species delineations reveal multiple cryptic lineages in elusive meiofaunal sea slugs

    Directory of Open Access Journals (Sweden)

    Jörger Katharina M

    2012-12-01

    Full Text Available Abstract Background Many marine meiofaunal species are reported to have wide distributions, which creates a paradox considering their hypothesized low dispersal abilities. Correlated with this paradox is an especially high taxonomic deficit for meiofauna, partly related to a lower taxonomic effort and partly to a high number of putative cryptic species. Molecular-based species delineation and barcoding approaches have been advocated for meiofaunal biodiversity assessments to speed up description processes and uncover cryptic lineages. However, these approaches show sensitivity to sampling coverage (taxonomic and geographic and the success rate has never been explored on mesopsammic Mollusca. Results We collected the meiofaunal sea-slug Pontohedyle (Acochlidia, Heterobranchia from 28 localities worldwide. With a traditional morphological approach, all specimens fall into two morphospecies. However, with a multi-marker genetic approach, we reveal multiple lineages that are reciprocally monophyletic on single and concatenated gene trees in phylogenetic analyses. These lineages are largely concordant with geographical and oceanographic parameters, leading to our primary species hypothesis (PSH. In parallel, we apply four independent methods of molecular based species delineation: General Mixed Yule Coalescent model (GMYC, statistical parsimony, Bayesian Species Delineation (BPP and Automatic Barcode Gap Discovery (ABGD. The secondary species hypothesis (SSH is gained by relying only on uncontradicted results of the different approaches (‘minimum consensus approach’, resulting in the discovery of a radiation of (at least 12 mainly cryptic species, 9 of them new to science, some sympatric and some allopatric with respect to ocean boundaries. However, the meiofaunal paradox still persists in some Pontohedyle species identified here with wide coastal and trans-archipelago distributions. Conclusions Our study confirms extensive, morphologically

  16. Feline genetics: clinical applications and genetic testing.

    Science.gov (United States)

    Lyons, Leslie A

    2010-11-01

    DNA testing for domestic cat diseases and appearance traits is a rapidly growing asset for veterinary medicine. Approximately 33 genes contain 50 mutations that cause feline health problems or alterations in the cat's appearance. A variety of commercial laboratories can now perform cat genetic diagnostics, allowing both the veterinary clinician and the private owner to obtain DNA test results. DNA is easily obtained from a cat via a buccal swab with a standard cotton bud or cytological brush, allowing DNA samples to be easily sent to any laboratory in the world. The DNA test results identify carriers of the traits, predict the incidence of traits from breeding programs, and influence medical prognoses and treatments. An overall goal of identifying these genetic mutations is the correction of the defect via gene therapies and designer drug therapies. Thus, genetic testing is an effective preventative medicine and a potential ultimate cure. However, genetic diagnostic tests may still be novel for many veterinary practitioners and their application in the clinical setting needs to have the same scrutiny as any other diagnostic procedure. This article will review the genetic tests for the domestic cat, potential sources of error for genetic testing, and the pros and cons of DNA results in veterinary medicine. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's internal genome. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Genome-wide scans for delineation of candidate genes regulating seed-protein content in chickpea

    Directory of Open Access Journals (Sweden)

    Hari Deo eUpadhyaya

    2016-03-01

    Full Text Available Identification of potential genes/alleles governing complex seed-protein content (SPC trait is essential in marker-assisted breeding for quality trait improvement of chickpea. Henceforth, the present study utilized an integrated genomics-assisted breeding strategy encompassing trait association analysis, selective genotyping in traditional bi-parental mapping population and differential expression profiling for the first-time to understand the complex genetic architecture of quantitative SPC trait in chickpea. For GWAS (genome-wide association study, high-throughput genotyping information of 16376 genome-based SNPs (single nucleotide polymorphism discovered from a structured population of 336 sequenced desi and kabuli accessions [with 150-200 kb LD (linkage disequilibrium decay] was utilized. This led to identification of seven most effective genomic loci (genes associated [10 to 20% with 41% combined PVE (phenotypic variation explained] with SPC trait in chickpea. Regardless of the diverse desi and kabuli genetic backgrounds, a comparable level of association potential of the identified seven genomic loci with SPC trait was observed. Five SPC-associated genes were validated successfully in parental accessions and homozygous individuals of an intra-specific desi RIL (recombinant inbred line mapping population (ICC 12299 x ICC 4958 by selective genotyping. The seed-specific expression, including differential up-regulation (> 4-fold of six SPC-associated genes particularly in accessions, parents and homozygous individuals of the aforementioned mapping population with high level of contrasting seed-protein content (21-22% was evident. Collectively, the integrated genomic approach delineated diverse naturally occurring novel functional SNP allelic variants in six potential candidate genes regulating SPC trait in chickpea. Of these, a non-synonymous SNP allele-carrying zinc finger transcription factor gene exhibiting strong association with SPC trait

  18. Epigenetic Alterations in Alzheimer’s Disease

    Science.gov (United States)

    Sanchez-Mut, Jose V.; Gräff, Johannes

    2015-01-01

    Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  19. Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands

    International Nuclear Information System (INIS)

    Nijkamp, Jasper; Haas-Kock, Danielle F.M. de; Beukema, Jannet C.; Neelis, Karen J.; Woutersen, Dankert; Ceha, Heleen; Rozema, Tom; Slot, Annerie; Vos-Westerman, Hanneke; Intven, Martijn; Spruit, Patty H.; Linden, Yvette van der; Geijsen, Debby; Verschueren, Karijn; Herk, Marcel B. van; Marijnen, Corrie A.M.

    2012-01-01

    Purpose: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer. Methods and materials: The CTV’s for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed. Results: The average delineated CTV volume decreased from 620 to 460 cc (p < 0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p = 0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively. Conclusions: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.

  20. Adaptive genetic markers discriminate migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid continued gene flow.

    Science.gov (United States)

    O'Malley, Kathleen G; Jacobson, Dave P; Kurth, Ryon; Dill, Allen J; Banks, Michael A

    2013-12-01

    Neutral genetic markers are routinely used to define distinct units within species that warrant discrete management. Human-induced changes to gene flow however may reduce the power of such an approach. We tested the efficiency of adaptive versus neutral genetic markers in differentiating temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid high gene flow owing to artificial propagation and habitat alteration. We compared seven putative migration timing genes to ten microsatellite loci in delineating three migratory groups of Chinook in the Feather River, CA: offspring of fall-run hatchery broodstock that returned as adults to freshwater in fall (fall run), spring-run offspring that returned in spring (spring run), and fall-run offspring that returned in spring (FRS). We found evidence for significant differentiation between the fall and federally listed threatened spring groups based on divergence at three circadian clock genes (OtsClock1b, OmyFbxw11, and Omy1009UW), but not neutral markers. We thus demonstrate the importance of genetic marker choice in resolving complex life history types. These findings directly impact conservation management strategies and add to previous evidence from Pacific and Atlantic salmon indicating that circadian clock genes influence migration timing.

  1. Differential response of rat strains to obesogenic diets underlines the importance of genetic makeup of an individual towards obesity.

    Science.gov (United States)

    Mn, Muralidhar; Smvk, Prasad; Battula, Kiran Kumar; Nv, Giridharan; Kalashikam, Rajender Rao

    2017-08-22

    Obesity, a multifactorial disorder, results from a chronic imbalance of energy intake vs. expenditure. Apart from excessive consumption of high calorie diet, genetic predisposition also seems to be equally important for the development of obesity. However, the role of genetic predisposition in the etiology of obesity has not been clearly delineated. The present study addresses this problem by selecting three rat strains (WNIN, F-344, SD) with different genetic backgrounds and exposing them to high calorie diets. Rat strains were fed HF, HS, and HFS diets and assessed for physical, metabolic, biochemical, inflammatory responses, and mRNA expression. Under these conditions: significant increase in body weight, visceral adiposity, oxidative stress and systemic pro-inflammatory status; the hallmarks of central obesity were noticed only in WNIN. Further, they developed altered glucose and lipid homeostasis by exhibiting insulin resistance, impaired glucose tolerance, dyslipidemia and fatty liver condition. The present study demonstrates that WNIN is more prone to develop obesity and associated co-morbidities under high calorie environment. It thus underlines the cumulative role of genetics (nature) and diet (nurture) towards the development of obesity, which is critical for understanding this epidemic and devising new strategies to control and manage this modern malady.

  2. Radio-anatomy Atlas for delineation SIRIADE web site: features and 1 year results

    International Nuclear Information System (INIS)

    Denisa, F.; Pointreau, Y.

    2010-01-01

    3-D conformal radiotherapy is based on accurate target volumes delineation. Radio-anatomy knowledge's are useful but sometimes difficult to obtain. Moreover, the sources of recommendations for volume definition are disparate. We thus developed a free radio-anatomy web site dedicated to volumes delineation for radiation-oncologists (www.siriade.org). This web site is a search engine allowing to access to delineation characteristics of main tumours illustrated with clinical cases. It does not aim to provide guidelines. Its main purpose is to provide an iconographic training support with frequent up-datings. We present the features of this web site and one year connexion statistics. (authors)

  3. Genetic algorithms

    Science.gov (United States)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  4. Genetic Mapping

    Science.gov (United States)

    ... greatly advanced genetics research. The improved quality of genetic data has reduced the time required to identify a ... cases, a matter of months or even weeks. Genetic mapping data generated by the HGP's laboratories is freely accessible ...

  5. Delineating the Diversity of Spinal Interneurons in Locomotor Circuits.

    Science.gov (United States)

    Gosgnach, Simon; Bikoff, Jay B; Dougherty, Kimberly J; El Manira, Abdeljabbar; Lanuza, Guillermo M; Zhang, Ying

    2017-11-08

    Locomotion is common to all animals and is essential for survival. Neural circuits located in the spinal cord have been shown to be necessary and sufficient for the generation and control of the basic locomotor rhythm by activating muscles on either side of the body in a specific sequence. Activity in these neural circuits determines the speed, gait pattern, and direction of movement, so the specific locomotor pattern generated relies on the diversity of the neurons within spinal locomotor circuits. Here, we review findings demonstrating that developmental genetics can be used to identify populations of neurons that comprise these circuits and focus on recent work indicating that many of these populations can be further subdivided into distinct subtypes, with each likely to play complementary functions during locomotion. Finally, we discuss data describing the manner in which these populations interact with each other to produce efficient, task-dependent locomotion. Copyright © 2017 the authors 0270-6474/17/3710835-07$15.00/0.

  6. Delineating wetland catchments and modeling hydrologic connectivity using lidar data and aerial imagery

    Science.gov (United States)

    In traditional watershed delineation and topographic modeling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM) to enforce flow continuity of water across the topographic surface to the watershed outlets. In re...

  7. A delineating procedure to retrieve relevant publication data in research areas : the case of nanocellulose

    NARCIS (Netherlands)

    Milanez, D.H.; Noyons, E.C.M.; Lopes, de Faria L.I.

    2016-01-01

    Advances concerning publication-level classification system have been demonstrated striking results by dealing properly with emergent, complex and interdisciplinary research areas, such as nanotechnology and nanocellulose. However, less attention has been paid to propose a delineating method to

  8. Geometrical Comparison Measures for Tumor Delineation, what do they mean for the Actual Dosis Plan?

    DEFF Research Database (Denmark)

    Hollensen, Christian; Persson, G.; Højgaard, L.

    2012-01-01

    Purpose/Objective: Gross tumour volume (GTV) delineation is central for radiotherapy planning. It provides the basis of the clinical target volume and finally the planning target volume (PTV) which is used for dose optimization. GTV delineations are prone to intermethod and inter......observer variation. In clinical studies this variation is commonly represented by geometrical volume comparison measures (GVCMs) as volume assessment, centre of mass and overlap. The correlation between these measures and the radiotherapy plan are however unclear. The aim of the present study is to investigate...... the correlation between GVCMs and the radiotherapy plans of patients with peripheral lung tumours. Materials and Methods: Peripheral lung tumours of 10 patients referred for stereotactic body radiotherapy in 2008 were delineated by 3 radiologists and 3 oncologists. From these GTV delineations 6 different...

  9. Genetic privacy.

    Science.gov (United States)

    Sankar, Pamela

    2003-01-01

    During the past 10 years, the number of genetic tests performed more than tripled, and public concern about genetic privacy emerged. The majority of states and the U.S. government have passed regulations protecting genetic information. However, research has shown that concerns about genetic privacy are disproportionate to known instances of information misuse. Beliefs in genetic determinacy explain some of the heightened concern about genetic privacy. Discussion of the debate over genetic testing within families illustrates the most recent response to genetic privacy concerns.

  10. A study of prostate delineation referenced against a gold standard created from the visible human data

    International Nuclear Information System (INIS)

    Gao Zhanrong; Wilkins, David; Eapen, Libni; Morash, Christopher; Wassef, Youssef; Gerig, Lee

    2007-01-01

    Purpose: To measure inter- and intra-observer variation and systematic error in CT based prostate delineation, where individual delineations are referenced against a gold standard produced from photographic anatomical images from the Visible Human Project (VHP). Materials and methods: The CT and anatomical images of the VHP male form the basic data set for this study. The gold standard was established based on 1 mm thick anatomical photographic images. These were registered against the 3 mm thick CT images that were used for target delineation. A total of 120 organ delineations were performed by six radiation oncologists. Results: The physician delineated prostate volume was on average 30% larger than the 'true' prostate volume, but on average included only 84% of the gold standard volume. Our study found a systematic delineation error such that posterior portions of the prostate were always missed while anteriorly some normal tissue was always defined as target. Conclusions: Our data suggest that radiation oncologists are more concerned with the unintentional inclusion of rectal tissue than they are in missing prostate volume. In contrast, they are likely to overextend the anterior boundary of the prostate to encompass normal tissue such as the bladder

  11. A Modular Low-Complexity ECG Delineation Algorithm for Real-Time Embedded Systems.

    Science.gov (United States)

    Bote, Jose Manuel; Recas, Joaquin; Rincon, Francisco; Atienza, David; Hermida, Roman

    2018-03-01

    This work presents a new modular and low-complexity algorithm for the delineation of the different ECG waves (QRS, P and T peaks, onsets, and end). Involving a reduced number of operations per second and having a small memory footprint, this algorithm is intended to perform real-time delineation on resource-constrained embedded systems. The modular design allows the algorithm to automatically adjust the delineation quality in runtime to a wide range of modes and sampling rates, from a ultralow-power mode when no arrhythmia is detected, in which the ECG is sampled at low frequency, to a complete high-accuracy delineation mode, in which the ECG is sampled at high frequency and all the ECG fiducial points are detected, in the case of arrhythmia. The delineation algorithm has been adjusted using the QT database, providing very high sensitivity and positive predictivity, and validated with the MIT database. The errors in the delineation of all the fiducial points are below the tolerances given by the Common Standards for Electrocardiography Committee in the high-accuracy mode, except for the P wave onset, for which the algorithm is above the agreed tolerances by only a fraction of the sample duration. The computational load for the ultralow-power 8-MHz TI MSP430 series microcontroller ranges from 0.2% to 8.5% according to the mode used.

  12. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer

    International Nuclear Information System (INIS)

    Offersen, Birgitte V.; Boersma, Liesbeth J.; Kirkove, Carine; Hol, Sandra; Aznar, Marianne C.; Biete Sola, Albert; Kirova, Youlia M.; Pignol, Jean-Philippe; Remouchamps, Vincent; Verhoeven, Karolien; Weltens, Caroline; Arenas, Meritxell; Gabrys, Dorota; Kopek, Neil; Krause, Mechthild; Lundstedt, Dan; Marinko, Tanja

    2015-01-01

    Background and purpose: Delineation of clinical target volumes (CTVs) is a weak link in radiation therapy (RT), and large inter-observer variation is seen in breast cancer patients. Several guidelines have been proposed, but most result in larger CTVs than based on conventional simulator-based RT. The aim was to develop a delineation guideline obtained by consensus between a broad European group of radiation oncologists. Material and methods: During ESTRO teaching courses on breast cancer, teachers sought consensus on delineation of CTV through dialogue based on cases. One teacher delineated CTV on CT scans of 2 patients, followed by discussion and adaptation of the delineation. The consensus established between teachers was sent to other teams working in the same field, both locally and on a national level, for their input. This was followed by developing a broad consensus based on discussions. Results: Borders of the CTV encompassing a 5 mm margin around the large veins, running through the regional lymph node levels were agreed, and for the breast/thoracic wall other vessels were pointed out to guide delineation, with comments on margins for patients with advanced breast cancer. Conclusion: The ESTRO consensus on CTV for elective RT of breast cancer, endorsed by a broad base of the radiation oncology community, is presented to improve consistency

  13. PLASTIC AND GLASS GREENHOUSES DETECTION AND DELINEATION FROM WORLDVIEW-2 SATELLITE IMAGERY

    Directory of Open Access Journals (Sweden)

    D. Koc-San

    2016-06-01

    Full Text Available Greenhouse detection using remote sensing technologies is an important research area for yield estimation, sustainable development, urban and rural planning and management. An approach was developed in this study for the detection and delineation of greenhouse areas from high resolution satellite imagery. Initially, the candidate greenhouse patches were detected using supervised classification techniques. For this purpose, Maximum Likelihood (ML, Random Forest (RF, and Support Vector Machines (SVM classification techniques were applied and compared. Then, sieve filter and morphological operations were performed for improving the classification results. Finally, the obtained candidate plastic and glass greenhouse areas were delineated using boundary tracing and Douglas Peucker line simplification algorithms. The proposed approach was implemented in the Kumluca district of Antalya, Turkey utilizing pan-sharpened WorldView-2 satellite imageries. Kumluca is the prominent district of Antalya with greenhouse cultivation and includes both plastic and glass greenhouses intensively. When the greenhouse classification results were analysed, it can be stated that the SVM classification provides most accurate results and RF classification follows this. The SVM classification overall accuracy was obtained as 90.28%. When the greenhouse boundary delineation results were considered, the plastic greenhouses were delineated with 92.11% accuracy, while glass greenhouses were delineated with 80.67% accuracy. The obtained results indicate that, generally plastic and glass greenhouses can be detected and delineated successfully from WorldView-2 satellite imagery.

  14. Automated Tree Crown Delineation and Biomass Estimation from Airborne LiDAR data: A Comparison of Statistical and Machine Learning Methods

    Science.gov (United States)

    Gleason, C. J.; Im, J.

    2011-12-01

    Airborne LiDAR remote sensing has been used effectively in assessing forest biomass because of its canopy penetrating effects and its ability to accurately describe the canopy surface. Current research in assessing biomass using airborne LiDAR focuses on either the individual tree as a base unit of study or statistical representations of a small aggregation of trees (i.e., plot level), and both methods usually rely on regression against field data to model the relationship between the LiDAR-derived data (e.g., volume) and biomass. This study estimates biomass for mixed forests and coniferous plantations (Picea Abies) within Heiberg Memorial Forest, Tully, NY, at both the plot and individual tree level. Plots are regularly spaced with a radius of 13m, and field data include diameter at breast height (dbh), tree height, and tree species. Field data collection and LiDAR data acquisition were seasonally coincident and both obtained in August of 2010. Resulting point cloud density was >5pts/m2. LiDAR data were processed to provide a canopy height surface, and a combination of watershed segmentation, active contouring, and genetic algorithm optimization was applied to delineate individual trees from the surface. This updated delineation method was shown to be more accurate than traditional watershed segmentation. Once trees had been delineated, four biomass estimation models were applied and compared: support vector regression (SVR), linear mixed effects regression (LME), random forest (RF), and Cubist regression. Candidate variables to be used in modeling were derived from the LiDAR surface, and include metrics of height, width, and volume per delineated tree footprint. Previously published allometric equations provided field estimates of biomass to inform the regressions and calculate their accuracy via leave-one-out cross validation. This study found that for forests such as found in the study area, aggregation of individual trees to form a plot-based estimate of

  15. Genetic counselling in the beta-thalassaemias

    Directory of Open Access Journals (Sweden)

    Adonis S. Ioannides

    2013-03-01

    Full Text Available The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses the contribution of genetic counsellingat each stage of this process in the context of new diagnostic techniques and therapeutic options and discusses some of the more challenging aspects such as genotype/ phenotype correlation and coinheritance of other genetic conditions or genetic modifiers.

  16. Major genomic mitochondrial lineages delineate early human expansions

    Directory of Open Access Journals (Sweden)

    Flores Carlos

    2001-08-01

    Full Text Available Abstract Background The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA sequences from 42 human lineages, representing major clades with known geographic assignation. Results We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. Conclusions The first detectable expansion occurred around 59,000–69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000–52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

  17. Delineation of facial archetypes by 3d averaging.

    Science.gov (United States)

    Shaweesh, Ashraf I; Thomas, C David L; Bankier, Agnes; Clement, John G

    2004-10-01

    The objective of this study was to investigate the feasibility of creating archetypal 3D faces through computerized 3D facial averaging. A 3D surface scanner Fiore and its software were used to acquire the 3D scans of the faces while 3D Rugle3 and locally-developed software generated the holistic facial averages. 3D facial averages were created from two ethnic groups; European and Japanese and from children with three previous genetic disorders; Williams syndrome, achondroplasia and Sotos syndrome as well as the normal control group. The method included averaging the corresponding depth (z) coordinates of the 3D facial scans. Compared with other face averaging techniques there was not any warping or filling in the spaces by interpolation; however, this facial average lacked colour information. The results showed that as few as 14 faces were sufficient to create an archetypal facial average. In turn this would make it practical to use face averaging as an identification tool in cases where it would be difficult to recruit a larger number of participants. In generating the average, correcting for size differences among faces was shown to adjust the average outlines of the facial features. It is assumed that 3D facial averaging would help in the identification of the ethnic status of persons whose identity may not be known with certainty. In clinical medicine, it would have a great potential for the diagnosis of syndromes with distinctive facial features. The system would also assist in the education of clinicians in the recognition and identification of such syndromes.

  18. Sir RA Fisher and the Evolution of Genetics

    Indian Academy of Sciences (India)

    quantitative genetics, a body of work that provides the conceptual underpinnings ... worked extensively with mutations that had large effects on structural ... altering the genetic composition of populations during adaptive ... exercise in ' writing.

  19. MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

    Science.gov (United States)

    Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

    2014-06-01

    Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

  20. Using the concentration-volume (C-V) fractal model in the delineation of gold mineralized zones within the Tepeoba porphyry Cu-Mo-Au, Balikesir, NW Turkey

    Science.gov (United States)

    Kumral, Mustafa; Abdelnasser, Amr; Karaman, Muhittin; Budakoglu, Murat

    2016-04-01

    The Tepeoba porphyry Cu-Mo-Au mineralization that located at the Biga peninsula (W Turkey) developed around the Eybek pluton concentrated at its southern contact. This mineralization that hosted in the hornfels rocks of Karakaya Complex is associated with three main alteration zones; potassic, phyllic and propylitic alterations along the fault controlled margins of the Eybek pluton and quartz stockwork veining as well as brecciation zones. As well as two mineralized zones were occurred in the mine area; hypogene and oxidation/supergene zone. The hypogene zone has differentiated alteration types; high potassic and low phyllic alteration, while the oxidation/supergene zone has high phyllic and propylitic alterations. This work deals with the delineation of gold mineralized zone within this porphyry deposit using the concentration-volume (C-V) fractal model. Five zones of gold were calculated using its power-law C-V relationship that revealed that the main phase of gold mineralization stated at 5.3083 ppm Au concentration. In addition, the C-V log-log plot shows that the highly and moderately Au mineralization zone developed in western part of deposit correlated with oxidation zone related to propylitic alteration. On the other hand, its weakly mineralization zone has a widespread in the hypogene zone related to potassic alteration. This refers to the enrichment of gold and depletion of copper at the oxidation/supergene zone is due to the oxidation/supergene alteration processes that enrich the deposits by the meteoric water. Keywords: Concentration-volume (C-V) fractal model; gold mineralized zone; Tepeoba porphyry Cu-Mo-Au; Balikesir; NW Turkey.

  1. Ensuring privacy in the study of pathogen genetics

    OpenAIRE

    Mehta, Sanjay R.; Vinterbo, Staal A.; Little, Susan J.

    2014-01-01

    Rapid growth in the genetic sequencing of pathogens in recent years has led to the creation of large sequence databases. This aggregated sequence data can be very useful for tracking and predicting epidemics of infectious diseases. However, the balance between the potential public health benefit and the risk to personal privacy for individuals whose genetic data (personal or pathogen) are included in such work has been difficult to delineate, because neither the true benefit nor the actual ri...

  2. Delineation and analysis of chromosomal regions specifying Yersinia pestis.

    Science.gov (United States)

    Derbise, Anne; Chenal-Francisque, Viviane; Huon, Christèle; Fayolle, Corinne; Demeure, Christian E; Chane-Woon-Ming, Béatrice; Médigue, Claudine; Hinnebusch, B Joseph; Carniel, Elisabeth

    2010-09-01

    Yersinia pestis, the causative agent of plague, has recently diverged from the less virulent enteropathogen Yersinia pseudotuberculosis. Its emergence has been characterized by massive genetic loss and inactivation and limited gene acquisition. The acquired genes include two plasmids, a filamentous phage, and a few chromosomal loci. The aim of this study was to characterize the chromosomal regions acquired by Y. pestis. Following in silico comparative analysis and PCR screening of 98 strains of Y. pseudotuberculosis and Y. pestis, we found that eight chromosomal loci (six regions [R1pe to R6pe] and two coding sequences [CDS1pe and CDS2pe]) specified Y. pestis. Signatures of integration by site specific or homologous recombination were identified for most of them. These acquisitions and the loss of ancestral DNA sequences were concentrated in a chromosomal region opposite to the origin of replication. The specific regions were acquired very early during Y. pestis evolution and were retained during its microevolution, suggesting that they might bring some selective advantages. Only one region (R3pe), predicted to carry a lambdoid prophage, is most likely no longer functional because of mutations. With the exception of R1pe and R2pe, which have the potential to encode a restriction/modification and a sugar transport system, respectively, no functions could be predicted for the other Y. pestis-specific loci. To determine the role of the eight chromosomal loci in the physiology and pathogenicity of the plague bacillus, each of them was individually deleted from the bacterial chromosome. None of the deletants exhibited defects during growth in vitro. Using the Xenopsylla cheopis flea model, all deletants retained the capacity to produce a stable and persistent infection and to block fleas. Similarly, none of the deletants caused any acute flea toxicity. In the mouse model of infection, all deletants were fully virulent upon subcutaneous or aerosol infections. Therefore

  3. Genetic diversity and landscape genetic structure of otter (Lutra lutra) populations in Europe

    DEFF Research Database (Denmark)

    Mucci, Nadia; Arrendal, Johanna; Ansorge, Hermann

    2010-01-01

    Eurasian otter populations strongly declined and partially disappeared due to global and local causes (habitat destruction, water pollution, human persecution) in parts of their continental range. Conservation strategies, based on reintroduction projects or restoration of dispersal corridors...... and landscape genetic analyses however indicate that local populations are genetically differentiated, perhaps as consequence of post-glacial demographic fluctuations and recent isolation. These results delineate a framework that should be used for implementing conservation programs in Europe, particularly...

  4. Delineating Individual Trees from Lidar Data: A Comparison of Vector- and Raster-based Segmentation Approaches

    Directory of Open Access Journals (Sweden)

    Maggi Kelly

    2013-08-01

    Full Text Available Light detection and ranging (lidar data is increasingly being used for ecosystem monitoring across geographic scales. This work concentrates on delineating individual trees in topographically-complex, mixed conifer forest across the California’s Sierra Nevada. We delineated individual trees using vector data and a 3D lidar point cloud segmentation algorithm, and using raster data with an object-based image analysis (OBIA of a canopy height model (CHM. The two approaches are compared to each other and to ground reference data. We used high density (9 pulses/m2, discreet lidar data and WorldView-2 imagery to delineate individual trees, and to classify them by species or species types. We also identified a new method to correct artifacts in a high-resolution CHM. Our main focus was to determine the difference between the two types of approaches and to identify the one that produces more realistic results. We compared the delineations via tree detection, tree heights, and the shape of the generated polygons. The tree height agreement was high between the two approaches and the ground data (r2: 0.93–0.96. Tree detection rates increased for more dominant trees (8–100 percent. The two approaches delineated tree boundaries that differed in shape: the lidar-approach produced fewer, more complex, and larger polygons that more closely resembled real forest structure.

  5. Tumor delineation: The weakest link in the search for accuracy in radiotherapy

    Directory of Open Access Journals (Sweden)

    Njeh C

    2008-01-01

    Full Text Available Radiotherapy is one of the most effective modalities for the treatment of cancer. However, there is a high degree of uncertainty associated with the target volume of most cancer sites. The sources of these uncertainties include, but are not limited to, the motion of the target, patient setup errors, patient movements, and the delineation of the target volume. Recently, many imaging techniques have been introduced to track the motion of tumors. The treatment delivery using these techniques is collectively called image-guided radiation therapy (IGRT. Ultimately, IGRT is only as good as the accuracy with which the target is known. There are reports of interobserver variability in tumor delineation across anatomical sites, but the widest ranges of variations have been reported for the delineation of head and neck tumors as well as esophageal and lung carcinomas. Significant interobserver variability in target delineation can be attributed to many factors including the impact of imaging and the influence of the observer (specialty, training, and personal bias. The visibility of the target can be greatly improved with the use of multimodality imaging by co-registration of CT with a second modality such as magnetic resonance imaging (MRI and/or positron emission tomography. Also, continuous education, training, and cross-collaboration of the radiation oncologist with other specialties can reduce the degree of variability in tumor delineation.

  6. Genetic and environmental interactions

    International Nuclear Information System (INIS)

    Strong, L.C.

    1977-01-01

    Cancer may result from a multistage process occurring over a long period of time. Presumably, initial and progressive stages of carcinogenesis may be modified by both genetic and environmental factors. Theoretically, genetic factors may alter susceptibility to the carcinogenic effects of an environmental agent at the initial exposure due to variation in metabolism of the carcinogen or variation in specific target cell response to the active carcinogen, or during the latent phase due to numerous factors that might increase the probability of tumor expression, including growth-promoting factors or immunodeficiency states. Observed genetic and environmental interactions in carcinogenesis include an association between genetically determined inducibility of aryl hydrocarbon hydroxylase and smoking-related cancers, familial susceptibility to certain environmental carcinogens, an association between hereditary disorders of mutagenesis and carcinogenesis, and enhancement of tissue-specific, dominantly inherited tumor predisposition by radiation. Multiple primary tumors occur frequently in genetically predisposed individuals. Specific markers for susceptibility must be sought in order that high-risk individuals be identified and appropriate measures taken for early cancer detection or prevention. Study of the nature of the genetically determined susceptibility and interactions with environmental agents may be revealing in the understanding of carcinogenesis in general

  7. An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese

    DEFF Research Database (Denmark)

    Graae, Anne-Sofie; Hollensted, Mette; Kloppenborg, Julie T

    2018-01-01

    and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children...... by linear regressions using an additive genetic model. In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3...

  8. Geographic object-based delineation of neighborhoods of Accra, Ghana using QuickBird satellite imagery.

    Science.gov (United States)

    Stow, Douglas A; Lippitt, Christopher D; Weeks, John R

    2010-08-01

    The objective was to test GEographic Object-based Image Analysis (GEOBIA) techniques for delineating neighborhoods of Accra, Ghana using QuickBird multispectral imagery. Two approaches to aggregating census enumeration areas (EAs) based on image-derived measures of vegetation objects were tested: (1) merging adjacent EAs according to vegetation measures and (2) image segmentation. Both approaches exploit readily available functions within commercial GEOBIA software. Image-derived neighborhood maps were compared to a reference map derived by spatial clustering of slum index values (from census data), to provide a relative assessment of potential map utility. A size-constrained iterative segmentation approach to aggregation was more successful than standard image segmentation or feature merge techniques. The segmentation approaches account for size and shape characteristics, enabling more realistic neighborhood boundaries to be delineated. The percentage of vegetation patches within each EA yielded more realistic delineation of potential neighborhoods than mean vegetation patch size per EA.

  9. Detection and delineation of underground septic tanks in sandy terrain using ground penetrating radar

    Science.gov (United States)

    Omolaiye, Gabriel Efomeh; Ayolabi, Elijah A.

    2010-09-01

    A ground penetrating radar (GPR) survey was conducted on the Lekki Peninsula, Lagos State, Nigeria. The primary target of the survey was the delineation of underground septic tanks (ST). A total of four GPR profiles were acquired on the survey site using Ramac X3M GPR equipment with a 250MHz antenna, chosen based on the depth of interest and resolution. An interpretable depth of penetration of 4.5m below the surface was achieved after processing. The method accurately delineated five underground ST. The tops of the ST were easily identified on the radargram based on the strong-amplitude anomalies, the length and the depths to the base of the ST were estimated with 99 and 73 percent confidence respectively. The continuous vertical profiles provide uninterrupted subsurface data along the lines of traverse, while the non-intrusive nature makes it an ideal tool for the accurate mapping and delineation of underground utilities.

  10. Genetic variant rs3750625 in the 3′UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site

    Science.gov (United States)

    Linnstaedt, Sarah D.; Walker, Margaret G.; Riker, Kyle D.; Nyland, Jennifer E.; Hu, JunMei; Rossi, Catherine; Swor, Robert A.; Jones, Jeffrey S.; Diatchenko, Luda; Bortsov, Andrey V.; Peak, David A.; McLean, Samuel A.

    2016-01-01

    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs. facilitation after both physical and psychological stress. To our knowledge the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3′UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased MSP in distressed individuals (stress*rs3750625 p = 0.043 for MVC cohort and p = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3′UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together these results suggest that ADRA2A rs3750625 contributes to post-stress MSP severity by modulating miR-34a regulation. PMID:27805929

  11. Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

    Science.gov (United States)

    Linnstaedt, Sarah D; Walker, Margaret G; Riker, Kyle D; Nyland, Jennifer E; Hu, JunMei; Rossi, Catherine; Swor, Robert A; Jones, Jeffrey S; Diatchenko, Luda; Bortsov, Andrey V; Peak, David A; McLean, Samuel A

    2017-02-01

    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

  12. Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

    Science.gov (United States)

    Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

    2013-03-01

    The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

  13. Using analytic element models to delineate drinking water source protection areas.

    Science.gov (United States)

    Raymond, Heather A; Bondoc, Michael; McGinnis, John; Metropulos, Kathy; Heider, Pat; Reed, Allison; Saines, Steve

    2006-01-01

    Since 1999, Ohio EPA hydrogeologists have used two analytic element models (AEMs), the proprietary software GFLOW and U.S. EPA's WhAEM, to delineate protection areas for 535 public water systems. Both models now use the GFLOW2001 solution engine, integrate well with Geographic Information System (GIS) technology, have a user-friendly graphical interface, are capable of simulating a variety of complex hydrogeologic settings, and do not rely upon a model grid. These features simplify the modeling process and enable AEMs to bridge the gap between existing simplistic delineation methods and more complex numerical models. Ohio EPA hydrogeologists demonstrated that WhAEM2000 and GFLOW2000 were capable of producing capture zones similar to more widely accepted models by applying the AEMs to eight sites that had been previously delineated using other methods. After the Ohio EPA delineated protection areas using AEMs, more simplistic delineation methods used by other states (volumetric equation and arbitrary fixed radii) were applied to the same water systems to compare the differences between various methods. GIS software and two-tailed paired t-tests were used to quantify the differences in protection areas and analyze the data. The results of this analysis demonstrate that AEMs typically produce significantly different protection areas than the most simplistic delineation methods, in terms of total area and shape. If the volumetric equation had been used instead of AEMs, Ohio would not have protected 265 km2 of critical upgradient area and would have overprotected 269 km2 of primarily downgradient land. Since an increasing number of land-use restrictions are being tied to drinking water protection areas, this analysis has broad policy implications.

  14. Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: A 'Big Brother' evaluation

    International Nuclear Information System (INIS)

    Steenbakkers, Roel J.H.M.; Duppen, Joop C.; Fitton, Isabelle; Deurloo, Kirsten E.I.; Zijp, Lambert; Uitterhoeve, Apollonia L.J.; Rodrigus, Patrick T.R.; Kramer, Gijsbert W.P.; Bussink, Johan; Jaeger, Katrien De; Belderbos, Jose S.A.; Hart, Augustinus A.M.; Nowak, Peter J.C.M.; Herk, Marcel van; Rasch, Coen R.N.

    2005-01-01

    Background and purpose: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. Patients and methods: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. Results: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P=0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm 2 ), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm 2 ), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. Conclusions: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between

  15. Clerics urge ban on altering germline cells.

    Science.gov (United States)

    Norman, C

    1983-06-24

    A resolution calling for a ban on genetic engineering of human reproductive cells has been signed by leaders of almost every major church group in the United States. Some of the religious leaders, while not certain that a total moratorium should be placed on altering germline cells, signed the statement in order to stimulate public debate on the issue. Legislation has recently been introduced in Congress to set up a committee to monitor genetic engineering and its human applications, but author Jeremy Rifkin, the impetus behind the church leaders' resolution, argues that such tampering threatens the gene pool and should be banned altogether.

  16. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  17. Using Cut-off grade isograms to delineate ore body and calculate parameter

    International Nuclear Information System (INIS)

    Yu Yongfeng; Zhu Xiaobing; Deng Yonghui

    2014-01-01

    Taking a uranium mine for an example, using cut-off grade isograms to achieve automatic delineation of ore body and calculation of parameters are explored. With center line of catalog sampling as baseline, the number of sampling and length of sampling constructing rectangular grid and grade as elevation value, isograms of cut-off grade were drawn, thus achieving the delineation of the ore body. Then, the other parameters of the ore body can be calculated. Compared with the traditional hand drawing method, the work efficiency was greatly improved, and the material inquiry was more convenient. (authors)

  18. Value of 18F-FDG PET-CT in nasopharyngeal carcinoma target delineation and radiotherapy boost

    International Nuclear Information System (INIS)

    Wang Ying; Feng Yanlin

    2011-01-01

    18 F-FDG PET-CT has widely used in nasopharyngeal carcinoma diagnosis and staging in recent years, it's effecten target volume delineation has received great attention. The article lays stress on the clinical research progress of 18 F-FDG PET-CT in the radiotherapy of nasopharyngeal carcinoma improve the accuracy of target delineation, reduce the difference of target delineation, guide the dose painting and boost. (authors)

  19. Delineating pathological pathways in a chemically induced mouse model of Gaucher disease.

    Science.gov (United States)

    Vardi, Ayelet; Zigdon, Hila; Meshcheriakova, Anna; Klein, Andrés D; Yaacobi, Chen; Eilam, Raya; Kenwood, Brandon M; Rahim, Ahad A; Massaro, Giulia; Merrill, Alfred H; Vitner, Einat B; Futerman, Anthony H

    2016-08-01

    Great interest has been shown in understanding the pathology of Gaucher disease (GD) due to the recently discovered genetic relationship with Parkinson's disease. For such studies, suitable animal models of GD are required. Chemical induction of GD by inhibition of acid β-glucosidase (GCase) using the irreversible inhibitor conduritol B-epoxide (CBE) is particularly attractive, although few systematic studies examining the effect of CBE on the development of symptoms associated with neurological forms of GD have been performed. We now demonstrate a correlation between the amount of CBE injected into mice and levels of accumulation of the GD substrates, glucosylceramide and glucosylsphingosine, and show that disease pathology, indicated by altered levels of pathological markers, depends on both the levels of accumulated lipids and the time at which their accumulation begins. Gene array analysis shows a remarkable similarity in the gene expression profiles of CBE-treated mice and a genetic GD mouse model, the Gba(flox/flox) ;nestin-Cre mouse, with 120 of the 144 genes up-regulated in CBE-treated mice also up-regulated in Gba(flox/flox) ;nestin-Cre mice. We also demonstrate that various aspects of neuropathology and some behavioural abnormalities can be arrested upon cessation of CBE treatment during a specific time window. Together, our data demonstrate that injection of mice with CBE provides a rapid and relatively easy way to induce symptoms typical of neuronal forms of GD. This is particularly useful when examining the role of specific biochemical pathways in GD pathology, since CBE can be injected into mice defective in components of putative pathological pathways, alleviating the need for time-consuming crossing of mice. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    Genetic algorithms (GAs) are computational optimisation schemes with an ... The algorithms solve optimisation problems ..... Genetic Algorithms in Search, Optimisation and Machine. Learning, Addison-Wesley Publishing Company, Inc. 1989.

  1. From Genetics to Genetic Algorithms

    Indian Academy of Sciences (India)

    artificial genetic system) string feature or ... called the genotype whereas it is called a structure in artificial genetic ... assigned a fitness value based on the cost function. Better ..... way it has produced complex, intelligent living organisms capable of ...

  2. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  3. Automatic Delineation of On-Line Head-And-Neck Computed Tomography Images: Toward On-Line Adaptive Radiotherapy

    International Nuclear Information System (INIS)

    Zhang Tiezhi; Chi Yuwei; Meldolesi, Elisa; Yan Di

    2007-01-01

    Purpose: To develop and validate a fully automatic region-of-interest (ROI) delineation method for on-line adaptive radiotherapy. Methods and Materials: On-line adaptive radiotherapy requires a robust and automatic image segmentation method to delineate ROIs in on-line volumetric images. We have implemented an atlas-based image segmentation method to automatically delineate ROIs of head-and-neck helical computed tomography images. A total of 32 daily computed tomography images from 7 head-and-neck patients were delineated using this automatic image segmentation method. Manually drawn contours on the daily images were used as references in the evaluation of automatically delineated ROIs. Two methods were used in quantitative validation: (1) the dice similarity coefficient index, which indicates the overlapping ratio between the manually and automatically delineated ROIs; and (2) the distance transformation, which yields the distances between the manually and automatically delineated ROI surfaces. Results: Automatic segmentation showed agreement with manual contouring. For most ROIs, the dice similarity coefficient indexes were approximately 0.8. Similarly, the distance transformation evaluation results showed that the distances between the manually and automatically delineated ROI surfaces were mostly within 3 mm. The distances between two surfaces had a mean of 1 mm and standard deviation of <2 mm in most ROIs. Conclusion: With atlas-based image segmentation, it is feasible to automatically delineate ROIs on the head-and-neck helical computed tomography images in on-line adaptive treatments

  4. About Genetic Counselors

    Science.gov (United States)

    ... clinical care in many areas of medicine. Assisted Reproductive Technology/Infertility Genetics Cancer Genetics Cardiovascular Genetics Cystic Fibrosis Genetics Fetal Intervention and Therapy Genetics Hematology Genetics Metabolic Genetics ...

  5. Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures.

    Science.gov (United States)

    Thevenon, Julien; Monnier, Nicole; Callier, Patrick; Dieterich, Klaus; Francoise, Michel; Montgomery, Tara; Kjaergaard, Susanne; Neas, Katherine; Dixon, Joanne; Dahm, Thomas Lee; Huet, Frédéric; Ragon, Clémence; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Duplomb, Laurence; Aubriot-Lorton, Marie-Hélène; Mugneret, Francine; Vokes, Steve A; Tucker, Haley W; Lunardi, Joël; Faivre, Laurence; Jouk, Pierre Simon; Thauvin-Robinet, Christel

    2014-12-01

    Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20-25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay. © 2014 Wiley Periodicals, Inc.

  6. The Pleurobemini (Bivalvia: Unionida) revisited: Molecular species delineation using a mitochondrial DNA gene reveals multiple conspecifics and undescribed species

    Science.gov (United States)

    Inoue, Kentaro; Hayes, David M.; Harris, John L.; Johnson, Nathan A.; Morrison, Cheryl L.; Eackles, Michael S.; King, Tim; Jones, Jess W.; Hallerman, Eric M.; Christian, Alan D.; Randklev, Charles R.

    2018-01-01

    The Pleurobemini (Bivalvia: Unionida) represent approximately one-third of freshwater mussel diversity in North America. Species identification within this group is challenging due to morphological convergence and phenotypic plasticity. Accurate species identification, including characterization of currently unrecognized taxa, is required to develop effective conservation strategies because many species in the group are imperiled. We examined 573 cox1 sequences from 110 currently recognized species (including 13 Fusconaia and 21 Pleurobema species) to understand phylogenetic relationships among pleurobemine species (mainly Fusconaia and Pleurobema) and to delineate species boundaries. The results of phylogenetic analyses showed no geographic structure within widespread species and illustrated a close relationship between Elliptio lanceolata and Parvaspina collina. Constraint tests supported monophyly of the genera Fusconaia and Pleurobema, including the subgenus P. (Sintoxia). Furthermore, results revealed multiple conspecifics, including P. hanleyianum and P. troschelianum, P. chattanoogaense and P. decisum, P. clava and P. oviforme, P. rubrum and P. sintoxia, F. askewi and F. lananensis, and F. cerina and F. flava. Species delimitation analyses identified three currently unrecognized taxa (two in Fusconaia and one in Pleurobema). Further investigation using additional genetic markers and other lines of evidence (e.g., morphology, life history, ecology) are necessary before any taxonomic changes are formalized.

  7. A novel method for delineation of oral mucosa for radiotherapy dose–response studies

    International Nuclear Information System (INIS)

    Dean, Jamie A.; Welsh, Liam C.; Gulliford, Sarah L.; Harrington, Kevin J.; Nutting, Christopher M.

    2015-01-01

    There is currently no standard method for delineating the oral mucosa and most attempts are oversimplified. A new method to obtain anatomically accurate contours of the oral mucosa surfaces was developed and applied to 11 patients. This is expected to represent an opportunity for improved toxicity modelling of oral mucositis

  8. A general methodology for three-dimensional analysis of variation in target volume delineation

    NARCIS (Netherlands)

    Remeijer, P.; Rasch, C.; Lebesque, J. V.; van Herk, M.

    1999-01-01

    A generic method for three-dimensional (3-D) evaluation of target volume delineation in multiple imaging modalities is presented. The evaluation includes geometrical and statistical methods to estimate observer differences and variability in defining the Gross Tumor Volume (GTV) in relation to the

  9. Instructor Strategic Ambiguity: Delineation of the Construct and Development of a Measure

    Science.gov (United States)

    Klyukovski, Andrei A.; Medlock-Klyukovski, Amanda L.

    2016-01-01

    This article presents research to delineate the construct of instructor strategic ambiguity (ISA) and develop a measure. The first study analyzed instructor uses of ambiguity, identified 18 strategies, and classified them into four categories. The second study developed an Instructor Strategic Ambiguity Measure (ISAM) for the college classroom.…

  10. Using the Gravity Model to Delineate a Trade Area: A Class Project.

    Science.gov (United States)

    Dzik, Anthony J.

    1992-01-01

    Reports that students who might be bored or intimidated by economic geographic theory become enthusiastic when they can apply it to their own experiences. Describes a class project involving fieldwork and in-class analysis on delineating the retail trade area of a small Ohio city. Includes three maps and mathematical formulae for data analysis.…

  11. An automatic, stagnation point based algorithm for the delineation of Wellhead Protection Areas

    Science.gov (United States)

    Tosco, Tiziana; Sethi, Rajandrea; di Molfetta, Antonio

    2008-07-01

    Time-related capture areas are usually delineated using the backward particle tracking method, releasing circles of equally spaced particles around each well. In this way, an accurate delineation often requires both a very high number of particles and a manual capture zone encirclement. The aim of this work was to propose an Automatic Protection Area (APA) delineation algorithm, which can be coupled with any model of flow and particle tracking. The computational time is here reduced, thanks to the use of a limited number of nonequally spaced particles. The particle starting positions are determined coupling forward particle tracking from the stagnation point, and backward particle tracking from the pumping well. The pathlines are postprocessed for a completely automatic delineation of closed perimeters of time-related capture zones. The APA algorithm was tested for a two-dimensional geometry, in homogeneous and nonhomogeneous aquifers, steady state flow conditions, single and multiple wells. Results show that the APA algorithm is robust and able to automatically and accurately reconstruct protection areas with a very small number of particles, also in complex scenarios.

  12. A New Wavelet-Based ECG Delineator for the Evaluation of the Ventricular Innervation

    DEFF Research Database (Denmark)

    Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

    2017-01-01

    T-wave amplitude (TWA) has been proposed as a marker of the innervation of the myocardium. Until now, TWA has been calculated manually or with poor algorithms, thus making its use not efficient in a clinical environment. We introduce a new wavelet-based algorithm for the delineation QRS complexes...

  13. Metrics for determining hydrophytic vegetation in wetland delineation: a clarification on the prevalence index

    Science.gov (United States)

    Diane De Steven

    2015-01-01

    A recent publication and an article in Wetland Science & Practice (Lichvar and Gillrich 2014b, 2014a) discuss two metrics for determining if vegetation is hydrophytic for purposes of U.S. wetland delineations, the Prevalence Index (PI) and a proposed Hydrophytic Cover Index (HCI). Based on Wentworth et al. (1988), the PI is a weighted average of ordinal scores (1-5...

  14. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, Maarten C.C.M. [Department of Radiation Oncology, University of Amsterdam (Netherlands)]. E-mail: m.c.hulshof@amc.uva.nl; Andel, George van [Department of Urology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Bel, Arjen [Department of Radiation Oncology, University of Amsterdam (Netherlands); Gangel, Pieter [Department of Radiation Oncology, University of Amsterdam (Netherlands); Kamer, Jeroen B. van de [Department of Radiation Oncology, University of Amsterdam (Netherlands)

    2007-07-15

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

  15. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

    International Nuclear Information System (INIS)

    Hulshof, Maarten C.C.M.; Andel, George van; Bel, Arjen; Gangel, Pieter; Kamer, Jeroen B. van de

    2007-01-01

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer

  16. Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas.

    Science.gov (United States)

    Hulshof, Maarten C C M; van Andel, George; Bel, Arjen; Gangel, Pieter; van de Kamer, Jeroen B

    2007-07-01

    A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

  17. Inter-observer delineation uncertainty in radiotherapy of peripheral lung tumours

    DEFF Research Database (Denmark)

    Persson, Gitte Fredberg; Nygaard, Ditte Eklund; Roed, Anders Peter

    was included in the study. In our clinical protocol the contrast enhanced PET/CT scan is primarily analysed by a specialist in nuclear medicine and a radiologists together. The PET positive volume is delineated by the specialist in nuclear medicine and only the CT scan and this contour is imported to Eclipse...

  18. Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Caravatta Luciana

    2012-06-01

    Full Text Available Abstract Background Radiotherapy (RT is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI in the preoperative and definitive treatment of pancreatic cancer. Methods The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. Results We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. Conclusions The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

  19. INVESTIGATION OF HYDROGEOLOGIC MAPPING TO DELINEATE PROTECTION ZONES AROUND SPRINGS: REPORT OF TWO CASE STUDIES

    Science.gov (United States)

    Methods commonly used to delineate protection zones for water-supply wells are often not directly applicable for springs. This investigation focuses on the use of hydrogeologic mapping methods to identify physical and hydrologic features that control ground-water flow to springs...

  20. delineating the jurassic to mid-cretaceous part of the pacific ...

    African Journals Online (AJOL)

    Mgina

    paleomagnetic field. This problem was solved by the formulation of the seamount paleomagnetism technique (Talwani 1965,. Plouff 1976, Parker et al. 1987). Following this, Sager and Pringle (1988) using mainly seamount paleomagnetic data delineated a well defined Pacific ... earth's surface and abuts six major and.

  1. Delineating wetland catchments and modeling hydrologic connectivity using lidar data and aerial imagery

    Directory of Open Access Journals (Sweden)

    Q. Wu

    2017-07-01

    Full Text Available In traditional watershed delineation and topographic modeling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM to enforce flow continuity of water across the topographic surface to the watershed outlets. In reality, however, many depressions in the DEM are actual wetland landscape features with seasonal to permanent inundation patterning characterized by nested hierarchical structures and dynamic filling–spilling–merging surface-water hydrological processes. Differentiating and appropriately processing such ecohydrologically meaningful features remains a major technical terrain-processing challenge, particularly as high-resolution spatial data are increasingly used to support modeling and geographic analysis needs. The objectives of this study were to delineate hierarchical wetland catchments and model their hydrologic connectivity using high-resolution lidar data and aerial imagery. The graph-theory-based contour tree method was used to delineate the hierarchical wetland catchments and characterize their geometric and topological properties. Potential hydrologic connectivity between wetlands and streams were simulated using the least-cost-path algorithm. The resulting flow network delineated potential flow paths connecting wetland depressions to each other or to the river network on scales finer than those available through the National Hydrography Dataset. The results demonstrated that our proposed framework is promising for improving overland flow simulation and hydrologic connectivity analysis.

  2. Multimodality Tumor Delineation and Predictive Modelling via Fuzzy-Fusion Deformable Models and Biological Potential Functions

    Science.gov (United States)

    Wasserman, Richard Marc

    The radiation therapy treatment planning (RTTP) process may be subdivided into three planning stages: gross tumor delineation, clinical target delineation, and modality dependent target definition. The research presented will focus on the first two planning tasks. A gross tumor target delineation methodology is proposed which focuses on the integration of MRI, CT, and PET imaging data towards the generation of a mathematically optimal tumor boundary. The solution to this problem is formulated within a framework integrating concepts from the fields of deformable modelling, region growing, fuzzy logic, and data fusion. The resulting fuzzy fusion algorithm can integrate both edge and region information from multiple medical modalities to delineate optimal regions of pathological tissue content. The subclinical boundaries of an infiltrating neoplasm cannot be determined explicitly via traditional imaging methods and are often defined to extend a fixed distance from the gross tumor boundary. In order to improve the clinical target definition process an estimation technique is proposed via which tumor growth may be modelled and subclinical growth predicted. An in vivo, macroscopic primary brain tumor growth model is presented, which may be fit to each patient undergoing treatment, allowing for the prediction of future growth and consequently the ability to estimate subclinical local invasion. Additionally, the patient specific in vivo tumor model will be of significant utility in multiple diagnostic clinical applications.

  3. Impact of FDG-PET/CT on Radiotherapy Volume Delineation in Non-Small-Cell Lung Cancer and Correlation of Imaging Stage With Pathologic Findings

    International Nuclear Information System (INIS)

    Faria, Sergio L.; Menard, Sonia; Devic, Slobodan; Sirois, Christian; Souhami, Luis; Lisbona, Robert; Freeman, Carolyn R.

    2008-01-01

    Purpose: Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is more accurate than CT in determining the extent of non-small-cell lung cancer. We performed a study to evaluate the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT without using any mathematical algorithm and to correlate the findings with the pathologic examination findings. Methods and Materials: A total of 32 patients with proven non-small-cell lung cancer, pathologic specimens from the mediastinum and lung primary, and pretreatment chest CT and FDG-PET/CT scans were studied. For each patient, two data sets of theoretical gross tumor volumes were contoured. One set was determined using the chest CT only, and the second, done separately, was based on the co-registered FDG-PET/CT data. The disease stage of each patient was determined using the TNM staging system for three data sets: the CT scan only, FDG-PET/CT scan, and pathologic findings. Results: Pathologic examination altered the CT-determined stage in 22 (69%) of 32 patients and the PET-determined stage in 16 (50%) of 32 patients. The most significant alterations were related to the N stage. PET altered the TNM stage in 15 (44%) of 32 patients compared with CT alone, but only 7 of these 15 alterations were confirmed by the pathologic findings. With respect to contouring the tumor volume for radiotherapy, PET altered the contour in 18 (56%) of 32 cases compared with CT alone. Conclusion: The contour of the tumor volume of non-small-cell lung cancer patients with co-registered FDG-PET/CT resulted in >50% alterations compared with CT targeting, findings similar to those of other publications. However, the significance of this change is unknown. Furthermore, pathologic examination showed that PET is not always accurate and histologic examination should be obtained to confirm the findings of PET whenever possible

  4. A wavelet-based ECG delineation algorithm for 32-bit integer online processing.

    Science.gov (United States)

    Di Marco, Luigi Y; Chiari, Lorenzo

    2011-04-03

    Since the first well-known electrocardiogram (ECG) delineator based on Wavelet Transform (WT) presented by Li et al. in 1995, a significant research effort has been devoted to the exploitation of this promising method. Its ability to reliably delineate the major waveform components (mono- or bi-phasic P wave, QRS, and mono- or bi-phasic T wave) would make it a suitable candidate for efficient online processing of ambulatory ECG signals. Unfortunately, previous implementations of this method adopt non-linear operators such as root mean square (RMS) or floating point algebra, which are computationally demanding. This paper presents a 32-bit integer, linear algebra advanced approach to online QRS detection and P-QRS-T waves delineation of a single lead ECG signal, based on WT. The QRS detector performance was validated on the MIT-BIH Arrhythmia Database (sensitivity Se = 99.77%, positive predictive value P+ = 99.86%, on 109010 annotated beats) and on the European ST-T Database (Se = 99.81%, P+ = 99.56%, on 788050 annotated beats). The ECG delineator was validated on the QT Database, showing a mean error between manual and automatic annotation below 1.5 samples for all fiducial points: P-onset, P-peak, P-offset, QRS-onset, QRS-offset, T-peak, T-offset, and a mean standard deviation comparable to other established methods. The proposed algorithm exhibits reliable QRS detection as well as accurate ECG delineation, in spite of a simple structure built on integer linear algebra.

  5. Optimising delineation accuracy of tumours in PET for radiotherapy planning using blind deconvolution

    International Nuclear Information System (INIS)

    Guvenis, A.; Koc, A.

    2015-01-01

    Positron emission tomography (PET) imaging has been proven to be useful in radiotherapy planning for the determination of the metabolically active regions of tumours. Delineation of tumours, however, is a difficult task in part due to high noise levels and the partial volume effects originating mainly from the low camera resolution. The goal of this work is to study the effect of blind deconvolution on tumour volume estimation accuracy for different computer-aided contouring methods. The blind deconvolution estimates the point spread function (PSF) of the imaging system in an iterative manner in a way that the likelihood of the given image being the convolution output is maximised. In this way, the PSF of the imaging system does not need to be known. Data were obtained from a NEMA NU-2 IQ-based phantom with a GE DSTE-16 PET/CT scanner. The artificial tumour diameters were 13, 17, 22, 28 and 37 mm with a target/background ratio of 4:1. The tumours were delineated before and after blind deconvolution. Student's two-tailed paired t-test showed a significant decrease in volume estimation error ( p < 0.001) when blind deconvolution was used in conjunction with computer-aided delineation methods. A manual delineation confirmation demonstrated an improvement from 26 to 16 % for the artificial tumour of size 37 mm while an improvement from 57 to 15 % was noted for the small tumour of 13 mm. Therefore, it can be concluded that blind deconvolution of reconstructed PET images may be used to increase tumour delineation accuracy. (authors)

  6. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics. MD. SAIMUL ISLAM. Articles written in Journal of Genetics. Volume 95 Issue 3 September 2016 pp 551-563 RESEARCH ARTICLE. Frequent alterations of SLIT2–ROBO1–CDC42 signalling pathway in breast cancer: clinicopathological correlation · RITTWIKA BHATTACHARYA NUPUR ...

  7. Species delineation using Bayesian model-based assignment tests: a case study using Chinese toad-headed agamas (genus Phrynocephalus

    Directory of Open Access Journals (Sweden)

    Fu Jinzhong

    2010-06-01

    Full Text Available Abstract Background Species are fundamental units in biology, yet much debate exists surrounding how we should delineate species in nature. Species discovery now requires the use of separate, corroborating datasets to quantify independently evolving lineages and test species criteria. However, the complexity of the speciation process has ushered in a need to infuse studies with new tools capable of aiding in species delineation. We suggest that model-based assignment tests are one such tool. This method circumvents constraints with traditional population genetic analyses and provides a novel means of describing cryptic and complex diversity in natural systems. Using toad-headed agamas of the Phrynocephalus vlangalii complex as a case study, we apply model-based assignment tests to microsatellite DNA data to test whether P. putjatia, a controversial species that closely resembles P. vlangalii morphologically, represents a valid species. Mitochondrial DNA and geographic data are also included to corroborate the assignment test results. Results Assignment tests revealed two distinct nuclear DNA clusters with 95% (230/243 of the individuals being assigned to one of the clusters with > 90% probability. The nuclear genomes of the two clusters remained distinct in sympatry, particularly at three syntopic sites, suggesting the existence of reproductive isolation between the identified clusters. In addition, a mitochondrial ND2 gene tree revealed two deeply diverged clades, which were largely congruent with the two nuclear DNA clusters, with a few exceptions. Historical mitochondrial introgression events between the two groups might explain the disagreement between the mitochondrial and nuclear DNA data. The nuclear DNA clusters and mitochondrial clades corresponded nicely to the hypothesized distributions of P. vlangalii and P. putjatia. Conclusions These results demonstrate that assignment tests based on microsatellite DNA data can be powerful tools

  8. Tomographic inversion of prismatic reflections for the delineation of steeply dipping structures; Inversion tomographique des reflexions prismatiques en vue de la delineation des structures tres pentees

    Energy Technology Data Exchange (ETDEWEB)

    Cavalca, M.

    2005-11-15

    Seismic imaging of salt flanks still remains a challenge for oil exploration. We propose here to exploit the kinematic information contained in prismatic reflections for the delineation of steeply dipping structures, such as faults or overhangs of salt bodies. This double reflection (on a steeply dipping structure and on a sedimentary interface) contains in fact precious information on the geometry of such structures, information that we try to exploit in travel-time tomography. We first carry out a precise kinematic analysis of these unusual reflections, to better understand under which conditions prismatic reflections can be observed in surface data; and we propose some interpretative guidelines, of great help for identifying such reflections in seismic data. We then study the tomographic inversion of prismatic reflections. Our first attempts at inverting prismatic reflections by standard travel-time tomography reveal a major difficulty due to the possible non definition of the standard forward map. We thus propose a new formulation of travel-time tomography which ensures the definition of the forward map and therefore a robust inversion of prismatic reflections. This approach shows its efficiency for delineating steeply dipping (and/or overhanging) structures on different synthetic experiments. We finally illustrate the benefit of jointly using the information contained in prismatic reflections and in primary events for the velocity model building (simultaneous determination of velocities and interface geometries), through the joint inversion of events interpreted and picked on a realistic synthetic dataset (BP-AIT 2004). (author)

  9. Using sequential indicator simulation to assess the uncertainty of delineating heavy-metal contaminated soils

    International Nuclear Information System (INIS)

    Juang, Kai-Wei; Chen, Yue-Shin; Lee, Dar-Yuan

    2004-01-01

    Mapping the spatial distribution of soil pollutants is essential for delineating contaminated areas. Currently, geostatistical interpolation, kriging, is increasingly used to estimate pollutant concentrations in soils. The kriging-based approach, indicator kriging (IK), may be used to model the uncertainty of mapping. However, a smoothing effect is usually produced when using kriging in pollutant mapping. The detailed spatial patterns of pollutants could, therefore, be lost. The local uncertainty of mapping pollutants derived by the IK technique is referred to as the conditional cumulative distribution function (ccdf) for one specific location (i.e. single-location uncertainty). The local uncertainty information obtained by IK is not sufficient as the uncertainty of mapping at several locations simultaneously (i.e. multi-location uncertainty or spatial uncertainty) is required to assess the reliability of the delineation of contaminated areas. The simulation approach, sequential indicator simulation (SIS), which has the ability to model not only single, but also multi-location uncertainties, was used, in this study, to assess the uncertainty of the delineation of heavy metal contaminated soils. To illustrate this, a data set of Cu concentrations in soil from Taiwan was used. The results show that contour maps of Cu concentrations generated by the SIS realizations exhausted all the spatial patterns of Cu concentrations without the smoothing effect found when using the kriging method. Based on the SIS realizations, the local uncertainty of Cu concentrations at a specific location of x', refers to the probability of the Cu concentration z(x') being higher than the defined threshold level of contamination (z c ). This can be written as Prob SIS [z(x')>z c ], representing the probability of contamination. The probability map of Prob SIS [z(x')>z c ] can then be used for delineating contaminated areas. In addition, the multi-location uncertainty of an area A,delineated

  10. Reduction of dose delivered to the rectum and bulb of the penis using MRI delineation for radiotherapy of the prostate

    NARCIS (Netherlands)

    Steenbakkers, Roel J. H. M.; Deurloo, Kirsten E. I.; Nowak, Peter J. C. M.; Lebesque, Joos V.; van Herk, Marcel; Rasch, Coen R. N.

    2003-01-01

    PURPOSE: The prostate volume delineated on MRI is smaller than on CT. The purpose of this study was to determine the influence of MRI- vs. CT-based prostate delineation using multiple observers on the dose to the target and organs at risk during external beam radiotherapy. MATERIALS AND METHODS: CT

  11. ASSESSING THE AGREEMENT BETWEEN EO-BASED SEMI-AUTOMATED LANDSLIDE MAPS WITH FUZZY MANUAL LANDSLIDE DELINEATION

    Directory of Open Access Journals (Sweden)

    F. Albrecht

    2017-09-01

    Full Text Available Landslide mapping benefits from the ever increasing availability of Earth Observation (EO data resulting from programmes like the Copernicus Sentinel missions and improved infrastructure for data access. However, there arises the need for improved automated landslide information extraction processes from EO data while the dominant method is still manual delineation. Object-based image analysis (OBIA provides the means for the fast and efficient extraction of landslide information. To prove its quality, automated results are often compared to manually delineated landslide maps. Although there is awareness of the uncertainties inherent in manual delineations, there is a lack of understanding how they affect the levels of agreement in a direct comparison of OBIA-derived landslide maps and manually derived landslide maps. In order to provide an improved reference, we present a fuzzy approach for the manual delineation of landslides on optical satellite images, thereby making the inherent uncertainties of the delineation explicit. The fuzzy manual delineation and the OBIA classification are compared by accuracy metrics accepted in the remote sensing community. We have tested this approach for high resolution (HR satellite images of three large landslides in Austria and Italy. We were able to show that the deviation of the OBIA result from the manual delineation can mainly be attributed to the uncertainty inherent in the manual delineation process, a relevant issue for the design of validation processes for OBIA-derived landslide maps.

  12. Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer

    DEFF Research Database (Denmark)

    Laugaard Lorenzen, Ebbe; Taylor, C. W.; Maraldo, M.

    2013-01-01

    receiving left breast radiotherapy. The delineations were carried out twice, first without guidelines and then with a set of common guidelines. RESULTS: For the heart, most spatial variation in delineation was near the base of the heart whereas for the LADCA most variation was in its length at the apex...

  13. Assessing the Agreement Between Eo-Based Semi-Automated Landslide Maps with Fuzzy Manual Landslide Delineation

    Science.gov (United States)

    Albrecht, F.; Hölbling, D.; Friedl, B.

    2017-09-01

    Landslide mapping benefits from the ever increasing availability of Earth Observation (EO) data resulting from programmes like the Copernicus Sentinel missions and improved infrastructure for data access. However, there arises the need for improved automated landslide information extraction processes from EO data while the dominant method is still manual delineation. Object-based image analysis (OBIA) provides the means for the fast and efficient extraction of landslide information. To prove its quality, automated results are often compared to manually delineated landslide maps. Although there is awareness of the uncertainties inherent in manual delineations, there is a lack of understanding how they affect the levels of agreement in a direct comparison of OBIA-derived landslide maps and manually derived landslide maps. In order to provide an improved reference, we present a fuzzy approach for the manual delineation of landslides on optical satellite images, thereby making the inherent uncertainties of the delineation explicit. The fuzzy manual delineation and the OBIA classification are compared by accuracy metrics accepted in the remote sensing community. We have tested this approach for high resolution (HR) satellite images of three large landslides in Austria and Italy. We were able to show that the deviation of the OBIA result from the manual delineation can mainly be attributed to the uncertainty inherent in the manual delineation process, a relevant issue for the design of validation processes for OBIA-derived landslide maps.

  14. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    International Nuclear Information System (INIS)

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

    2014-01-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  15. How large is the Upper Indus Basin? The pitfalls of auto-delineation using DEMs

    Science.gov (United States)

    Khan, Asif; Richards, Keith S.; Parker, Geoffrey T.; McRobie, Allan; Mukhopadhyay, Biswajit

    2014-02-01

    Extraction of watershed areas from Digital Elevation Models (DEMs) is increasingly required in a variety of environmental analyses. It is facilitated by the availability of DEMs based on remotely sensed data, and by Geographical Information System (GIS) software. However, accurate delineation depends on the quality of the DEM and the methodology adopted. This paper considers automated and supervised delineation in a case study of the Upper Indus Basin (UIB), Pakistan, for which published estimates of the basin area show significant disagreement, ranging from 166,000 to 266,000 km2. Automated delineation used ArcGIS Archydro and hydrology tools applied to three good quality DEMs (two from SRTM data with 90m resolution, and one from 30m resolution ASTER data). Automatic delineation defined a basin area of c.440,000 km2 for the UIB, but included a large area of internal drainage in the western Tibetan Plateau. It is shown that discrepancies between different estimates reflect differences in the initial extent of the DEM used for watershed delineation, and the unchecked effect of iterative pit-filling of the DEM (going beyond the filling of erroneous pixels to filling entire closed basins). For the UIB we have identified critical points where spurious addition of catchment area has arisen, and use Google Earth to examine the geomorphology adjacent to these points, and also examine the basin boundary data provided by the HydroSHEDS database. We show that the Pangong Tso watershed and some other areas in the western Tibetan plateau are not part of the UIB, but are areas of internal drainage. Our best estimate of the area of the Upper Indus Basin (at Besham Qila) is 164,867 km2 based on the SRTM DEM, and 164,853 km2 using the ASTER DEM). This matches the catchment area measured by WAPDA SWHP. An important lesson from this investigation is that one should not rely on automated delineation, as iterative pit-filling can produce spurious drainage networks and basins, when

  16. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    Energy Technology Data Exchange (ETDEWEB)

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den [UMC Utrecht, Utrecht, Utrecht (Netherlands)

    2014-06-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  17. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  18. Preliminary evaluation of alterant geophysical tomography in welded tuff

    International Nuclear Information System (INIS)

    Ramirez, A.L.; Daily, W.D.

    1985-01-01

    The ability of alterant geophysical tomography to delineate flow paths in a welded tuff rock mass has been preliminarily evaluated based on the results of a field experiment. Electromagnetic measurements were made before, during and after a water-based, dye tracer flowed through the rock mass. Alterant geophysical tomographs were generated and compared with independent evidence - borescope logs, neutron logs and dyed rock samples. Anomalies present in the tomograph match the location and orientation of fractures mapped with a borescope. The location of tracer-stained fractures coincides with the location of some image anomalies; other geophysical anomalies exist where tracer-stained fractures were not observed, perhaps due to poor core recovery. Additional drilling to locate stained flow paths and other experiments are planned so that the applicability of the technique can be further evaluated

  19. Genetic Engineering

    Science.gov (United States)

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  20. Correlation of infrared reflectance ratios at 2.3 microns/1.6 micron and 1.1 micron/1.6 micron with delta O-18 values delineating fossil hydrothermal systems in the Idaho batholith

    Science.gov (United States)

    Gillespie, A. R.; Criss, R. E.

    1983-01-01

    Reflectance ratios from laboratory spectra and airborne multispectral images are found to be strongly correlated with delta O-18 values of granite rocks in the Idaho batholith. The correlation is largely a result of interactions between hot water and rock, which lowered the delta O-18 values of the rocks and produced secondary hydrous material. Maps of the ratio of reflectivities at 2.3 and 1.6 microns should delineate fossil hydrothermal systems and provide estimates of alteration intensity. However, hydrous minerals produced during deuteric alteration or weathering cannot be unambiguously distinguished in remotely sensed images from the products of propylitic alteration without the use of narrow-band scanners. The reflectivity at 1.6 micron is strongly correlated with rock density and may be useful in distinguishing rock types in granitic terranes.

  1. Detection and delineation of waste trenches by geophysical methods at Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Selfridge, R.J.

    1987-01-01

    Detection and delineation of waste trenches at hazardous waste sites are needed before actual implementation of site corrective measures. In a field study conducted in Solid Waste Storage Area 4 (SWSA4) at Oak Ridge National Laboratory (ORNL), surface geophysical techniques were used to assist in the delineation of waste trenches. A magnetometer/gradiometer survey was used to detect ferrous metals buried at the site. An electromagnetic ground conductivity survey was used to measure the electrical conductivity of the subsurface and aided in supporting the magnetometer/gradiometer results. Results from the two techniques were complimentary and easily integrated into a final interpretation. The reliability, efficiency, and worker safety benefits of these techniques offer a nondestructive surface technique for locating buried waste trenches

  2. Intrinsic properties of channel network structure and the hierarchical classification approach for stream-limits delineation

    Energy Technology Data Exchange (ETDEWEB)

    Afana, A.; Barrio, G. del

    2009-07-01

    Delineation of drainage networks is an essential task in hydrological and geomorphologic analysis. Manual channel definition depends on topographic contrast and is highly subjective, leading to important errors at high resolutions. different automatic methods have proposed the use of a constant threshold of up sole contributing are to define channel initiation. Actually, these are the most commonly used for the automatic-channel network extraction from Digital Models (DEMs). However, these methods fall to detect and appropriate threshold when the basin is made up to heterogeneous sub-zones, as they only work either lumped or locally. In this study, the critical threshold area for channel delineation has been defined through the analysis of dominant geometric and topologic properties of stream network formation. (Author) 5 refs.

  3. Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Kim

    2018-02-01

    Full Text Available PURPOSE: Phyllodes tumors (PTs of the breast are rare, accounting for less than 1% of all breast tumors. Among PTs, malignant PTs (MPTs have malignant characteristics and distant metastases occur in about 20% to 30% of MPTs. However, there is no effective treatment for MPTs with distant metastasis, resulting in an abject prognosis. We performed targeted deep sequencing on PTs to identify the associations between genetic alterations and clinical prognosis. METHODS: We performed targeted deep sequencing to evaluate the genetic characteristics of PTs and analyzed the relationships between clinical and genetic characteristics. RESULTS: A total of 17 PTs were collected between 2001 and 2012. Histologic review was performed by pathologists. The samples included three benign PTs, one borderline PT, and 13 MPTs. The most frequently detected genetic alteration occurred in the TERT promoter region (70.6%, followed by MED12 (64.7%. EGFR amplification and TP53 alteration were detected in four MPTs without genetic alterations in MED12 and TERT promoter regions. Genetic alterations of RARA and ZNF703 were repeatedly found in PTs with local recurrence, and genetic alterations of SETD2, BRCA2, and TSC1 were detected in PTs with distant metastasis. Especially, MPT harboring PTEN and RB1 copy number deletion showed rapid disease progression. CONCLUSIONS: In this study, we provide genetic characterization and potential therapeutic target for this rare, potentially lethal disease. Further large-scale comprehensive genetic study and functional validation are warranted.

  4. Near-census Delineation of Laterally Organized Geomorphic Zones and Associated Sub-width Fluvial Landforms

    Science.gov (United States)

    Pasternack, G. B.; Hopkins, C.

    2017-12-01

    A river channel and its associated riparian corridor exhibit a pattern of nested, geomorphically imprinted, lateral inundation zones (IZs). Each zone plays a key role in fluvial geomorphic processes and ecological functions. Within each zone, distinct landforms (aka geomorphic or morphological units, MUs) reside at the 0.1-10 channel width scale. These features are basic units linking river corridor morphology with local ecosystem services. Objective, automated delineation of nested inundation zones and morphological units remains a significant scientific challenge. This study describes and demonstrates new, objective methods for solving this problem, using the 35-km alluvial lower Yuba River as a testbed. A detrended, high-resolution digital elevation model constructed from near-census topographic and bathymetric data was produced and used in a hypsograph analysis, a commonly used method in oceanographic studies capable of identifying slope breaks at IZ transitions. Geomorphic interpretation mindful of the river's setting was required to properly describe each IZ identified by the hypsograph analysis. Then, a 2D hydrodynamic model was used to determine what flow yields the wetted area that most closely matches each IZ domain. The model also provided meter-scale rasters of depth and velocity useful for MU mapping. Even though MUs are discharge-independent landforms, they can be revealed by analyzing their overlying hydraulics at low flows. Baseflow depth and velocity rasters are used along with a hydraulic landform classification system to quantitatively delineate in-channel bed MU types. In-channel bar and off-channel flood and valley MUs are delineated using a combination of hydraulic and geomorphic indicators, such as depth and velocity rasters for different discharges, topographic contours, NAIP imagery, and a raster of vegetation. The ability to objectively delineate inundation zones and morphological units in tandem allows for better informed river management

  5. Study on delineation of tumor volume of primary locally advanced nasopharyngeal carcinoma after induction chemotherapy

    International Nuclear Information System (INIS)

    Long Jinhua; Dong Shi; Jin Feng; Wu Weili; Gan Jiaying; Chen Haixia; Li Yuanyuan; Gong Xiuyun

    2012-01-01

    Objective: To investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better. Methods: Between Mar 2010 to Jan 2011, 11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy, target volumes were delineated based on fused CT imaging before and after IC following project determination. Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTV nx in order to ensure radical doses for the imaging tumor volume before IC, the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test. Results: Before and after IC, the average volumes of GTV nx were respectively 44.72 cm 3 and 28.87 (t=3.89, P=0.003), the average volumes of GTV nd were respectively 32.76 cm 3 and 19.82 cm 3 (t=2.47, P=0.033), the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased (t=2.93-4.59, all P<0.05). Conclusions: LANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy shows significant shrinkage of tumor volume. The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC. (authors)

  6. Description and application of capture zone delineation for a wellfield at Hilton Head Island, South Carolina

    Science.gov (United States)

    Landmeyer, J.E.

    1994-01-01

    Ground-water capture zone boundaries for individual pumped wells in a confined aquffer were delineated by using groundwater models. Both analytical and numerical (semi-analytical) models that more accurately represent the $round-water-flow system were used. All models delineated 2-dimensional boundaries (capture zones) that represent the areal extent of groundwater contribution to a pumped well. The resultant capture zones were evaluated on the basis of the ability of each model to realistically rapresent the part of the ground-water-flow system that contributed water to the pumped wells. Analytical models used were based on a fixed radius approach, and induded; an arbitrary radius model, a calculated fixed radius model based on the volumetric-flow equation with a time-of-travel criterion, and a calculated fixed radius model derived from modification of the Theis model with a drawdown criterion. Numerical models used induded the 2-dimensional, finite-difference models RESSQC and MWCAP. The arbitrary radius and Theis analytical models delineated capture zone boundaries that compared least favorably with capture zones delineated using the volumetric-flow analytical model and both numerical models. The numerical models produced more hydrologically reasonable capture zones (that were oriented parallel to the regional flow direction) than the volumetric-flow equation. The RESSQC numerical model computed more hydrologically realistic capture zones than the MWCAP numerical model by accounting for changes in the shape of capture zones caused by multiple-well interference. The capture zone boundaries generated by using both analytical and numerical models indicated that the curnmtly used 100-foot radius of protection around a wellhead in South Carolina is an underestimate of the extent of ground-water capture for pumped wetis in this particular wellfield in the Upper Floridan aquifer. The arbitrary fixed radius of 100 feet was shown to underestimate the upgradient

  7. Benchmark of Client and Server-Side Catchment Delineation Approaches on Web-Based Systems

    Science.gov (United States)

    Demir, I.; Sermet, M. Y.; Sit, M. A.

    2016-12-01

    Recent advances in internet and cyberinfrastructure technologies have provided the capability to acquire large scale spatial data from various gauges and sensor networks. The collection of environmental data increased demand for applications which are capable of managing and processing large-scale and high-resolution data sets. With the amount and resolution of data sets provided, one of the challenging tasks for organizing and customizing hydrological data sets is delineation of watersheds on demand. Watershed delineation is a process for creating a boundary that represents the contributing area for a specific control point or water outlet, with intent of characterization and analysis of portions of a study area. Although many GIS tools and software for watershed analysis are available on desktop systems, there is a need for web-based and client-side techniques for creating a dynamic and interactive environment for exploring hydrological data. In this project, we demonstrated several watershed delineation techniques on the web with various techniques implemented on the client-side using JavaScript and WebGL, and on the server-side using Python and C++. We also developed a client-side GPGPU (General Purpose Graphical Processing Unit) algorithm to analyze high-resolution terrain data for watershed delineation which allows parallelization using GPU. The web-based real-time analysis of watershed segmentation can be helpful for decision-makers and interested stakeholders while eliminating the need of installing complex software packages and dealing with large-scale data sets. Utilization of the client-side hardware resources also eliminates the need of servers due its crowdsourcing nature. Our goal for future work is to improve other hydrologic analysis methods such as rain flow tracking by adapting presented approaches.

  8. Atlas-based delineation of lymph node levels in head and neck computed tomography images

    International Nuclear Information System (INIS)

    Commowick, Olivier; Gregoire, Vincent; Malandain, Gregoire

    2008-01-01

    Purpose: Radiotherapy planning requires accurate delineations of the tumor and of the critical structures. Atlas-based segmentation has been shown to be very efficient to automatically delineate brain critical structures. We therefore propose to construct an anatomical atlas of the head and neck region. Methods and materials: Due to the high anatomical variability of this region, an atlas built from a single image as for the brain is not adequate. We address this issue by building a symmetric atlas from a database of manually segmented images. First, we develop an atlas construction method and apply it to a database of 45 Computed Tomography (CT) images from patients with node-negative pharyngo-laryngeal squamous cell carcinoma manually delineated for radiotherapy. Then, we qualitatively and quantitatively evaluate the results generated by the built atlas based on Leave-One-Out framework on the database. Results: We present qualitative and quantitative results using this atlas construction method. The evaluation was performed on a subset of 12 patients among the original CT database of 45 patients. Qualitative results depict visually well delineated structures. The quantitative results are also good, with an error with respect to the best achievable results ranging from 0.196 to 0.404 with a mean of 0.253. Conclusions: These results show the feasibility of using such an atlas for radiotherapy planning. Many perspectives are raised from this work ranging from extensive validation to the construction of several atlases representing sub-populations, to account for large inter-patient variabilities, and populations with node-positive tumors

  9. Delineating wetland catchments and modeling hydrologic connectivity using LiDAR data and aerial imagery

    OpenAIRE

    Wu, Qiusheng; Lane, Charles R.

    2017-01-01

    In traditional watershed delineation and topographic modeling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM) to enforce flow continuity of water across the topographic surface to the watershed outlets. In reality, however, many depressions in the DEM are actual wetland landscape features that are seldom fully filled with water. For instance, wetland depressions in the Prairie Pothole Region (PPR) are seasonally to perman...

  10. Delineation of Oil – Polluted Sites in Ibeno LGA, Nigeria, Using Geophysical Techniques

    OpenAIRE

    Ime R. Udotong; Justina I. R. Udotong; Ofonime U. M. John

    2015-01-01

    Ibeno, Nigeria hosts the operational base of Mobil Producing Nigeria Unlimited (MPNU), a subsidiary of ExxonMobil and the current highest oil & condensate producer in Nigeria. Besides MPNU, other oil companies operate onshore, on the continental shelf and deep offshore of the Atlantic Ocean in Ibeno, Nigeria. This study was designed to delineate oil polluted sites in Ibeno, Nigeria using geophysical methods of electrical resistivity (ER) and ground penetrating radar (GPR)...

  11. Delineation of post - i ndustrial landscapes of the Upper Silesian corridor in the Basin of Ostrava

    Czech Academy of Sciences Publication Activity Database

    Kolejka, Jaromír; Klimánek, M.; Martinát, Stanislav; Ruda, A.

    2013-01-01

    Roč. 1, č. 3 (2013), s. 21-34 ISSN 2354-0079 R&D Projects: GA AV ČR IAA300860903 Institutional support: RVO:68145535 Keywords : delineation * brownfields * Upper Silesia * GIS Subject RIV: DE - Earth Magnetism, Geodesy, Geography http://environ.ses.us.edu.pl/download/2013.1.3/2013.1.3.%20Full%20text%2021-34.pdf

  12. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients.

    Science.gov (United States)

    Dolz, J; Kirişli, H A; Fechter, T; Karnitzki, S; Oehlke, O; Nestle, U; Vermandel, M; Massoptier, L

    2016-05-01

    Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs required for thoracic radiation therapy has

  13. Iterative Otsu's method for OCT improved delineation in the aorta wall

    Science.gov (United States)

    Alonso, Daniel; Real, Eusebio; Val-Bernal, José F.; Revuelta, José M.; Pontón, Alejandro; Calvo Díez, Marta; Mayorga, Marta; López-Higuera, José M.; Conde, Olga M.

    2015-07-01

    Degradation of human ascending thoracic aorta has been visualized with Optical Coherence Tomography (OCT). OCT images of the vessel wall exhibit structural degradation in the media layer of the artery, being this disorder the final trigger of the pathology. The degeneration in the vessel wall appears as low-reflectivity areas due to different optical properties of acidic polysaccharides and mucopolysaccharides in contrast with typical ordered structure of smooth muscle cells, elastin and collagen fibers. An OCT dimension indicator of wall degradation can be generated upon the spatial quantification of the extension of degraded areas in a similar way as conventional histopathology. This proposed OCT marker can offer in the future a real-time clinical perception of the vessel status to help cardiovascular surgeons in vessel repair interventions. However, the delineation of degraded areas on the B-scan image from OCT is sometimes difficult due to presence of speckle noise, variable signal to noise ratio (SNR) conditions on the measurement process, etc. Degraded areas can be delimited by basic thresholding techniques taking advantage of disorders evidences in B-scan images, but this delineation is not optimum in the aorta samples and requires complex additional processing stages. This work proposes an optimized delineation of degraded areas within the aorta wall, robust to noisy environments, based on the iterative application of Otsu's thresholding method. Results improve the delineation of wall anomalies compared with the simple application of the algorithm. Achievements could be also transferred to other clinical scenarios: carotid arteries, aorto-iliac or ilio-femoral sections, intracranial, etc.

  14. An automatized frequency analysis for vine plot detection and delineation in remote sensing

    OpenAIRE

    Delenne , Carole; Rabatel , G.; Deshayes , M.

    2008-01-01

    The availability of an automatic tool for vine plot detection, delineation, and characterization would be very useful for management purposes. An automatic and recursive process using frequency analysis (with Fourier transform and Gabor filters) has been developed to meet this need. This results in the determination of vine plot boundary and accurate estimation of interrow width and row orientation. To foster large-scale applications, tests and validation have been carried out on standard ver...

  15. Modeling fire susceptibility to delineate wildland-urban interface for municipal-scale fire risk management.

    Science.gov (United States)

    Whitman, Ellen; Rapaport, Eric; Sherren, Kate

    2013-12-01

    The wildland-urban interface (WUI) is the region where development meets and intermingles with wildlands. The WUI has an elevated fire risk due to the proximity of development and residents to wildlands with natural wildfire regimes. Existing methods of delineating WUI are typically applied over a large region, use proxies for risk, and do not consider site-specific fire hazard drivers. While these models are appropriate for federal and provincial risk management, municipal managers require models intended for smaller regions. The model developed here uses the Burn-P3 fire behavior model to model WUI from local fire susceptibility (FS) in two study communities. Forest fuel code (FFC) maps for the study communities were modified using remote sensing data to produce detailed forest edges, including ladder fuels, update data currency, and add buildings and roads. The modified FFC maps used in Burn-P3 produced bimodal FS distributions for each community. The WUI in these communities was delineated as areas within community bounds where FS was greater than or equal to -1 SD from the mean FS value ([Formula: see text]), which fell in the trough of the bimodal distribution. The WUI so delineated conformed to the definition of WUI. This model extends WUI modeling for broader risk management initiatives for municipal management of risk, as it (a) considers site-specific drivers of fire behavior; (b) models risk, represented by WUI, specific to a community; and, (c) does not use proxies for risk.

  16. Interobserver Delineation variation using CT versus combined CT + MRI in intensity- modulated radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Villeirs, G.M.; Verstraete, K.L.; Vaerenbergh, K. van; Vakaet, L.; Bral, S.; Claus, F.; Neve, W.J. de; Meerleer, G.O. de

    2005-01-01

    Purpose: to quantify interobserver variation of prostate and seminal vesicle delineations using CT only versus CT + MRI in consensus reading with a radiologist. Material and methods: the prostate and seminal vesicles of 13 patients treated with intensity-modulated radiotherapy for prostatic adenocarcinoma were retrospectively delineated by three radiation oncologists on CT only and on CT + MRI in consensus reading with a radiologist. The volumes and margin positions were calculated and intermodality and interobserver variations were assessed for the clinical target volume (CTV), seminal vesicles, prostate and three prostatic subdivisions (apical, middle and basal third). Results: using CT + MRI as compared to CT alone, the mean CTV, prostate and seminal vesicle volumes significantly decreased by 6.54%, 5.21% and 10.47%, respectively. More importantly, their standard deviations significantly decreased by 63.06%, 62.65% and 44.83%, respectively. The highest level of variation was found at the prostatic apex, followed by the prostatic base and seminal vesicles. Conclusion: addition of MRI to CT in consensus reading with a radiologist results in a moderate decrease of the CTV, but an important decrease of the interobserver delineation variation, especially at the prostatic apex. (orig.)

  17. Delineating species with DNA barcodes: a case of taxon dependent method performance in moths.

    Directory of Open Access Journals (Sweden)

    Mari Kekkonen

    Full Text Available The accelerating loss of biodiversity has created a need for more effective ways to discover species. Novel algorithmic approaches for analyzing sequence data combined with rapidly expanding DNA barcode libraries provide a potential solution. While several analytical methods are available for the delineation of operational taxonomic units (OTUs, few studies have compared their performance. This study compares the performance of one morphology-based and four DNA-based (BIN, parsimony networks, ABGD, GMYC methods on two groups of gelechioid moths. It examines 92 species of Finnish Gelechiinae and 103 species of Australian Elachistinae which were delineated by traditional taxonomy. The results reveal a striking difference in performance between the two taxa with all four DNA-based methods. OTU counts in the Elachistinae showed a wider range and a relatively low (ca. 65% OTU match with reference species while OTU counts were more congruent and performance was higher (ca. 90% in the Gelechiinae. Performance rose when only monophyletic species were compared, but the taxon-dependence remained. None of the DNA-based methods produced a correct match with non-monophyletic species, but singletons were handled well. A simulated test of morphospecies-grouping performed very poorly in revealing taxon diversity in these small, dull-colored moths. Despite the strong performance of analyses based on DNA barcodes, species delineated using single-locus mtDNA data are best viewed as OTUs that require validation by subsequent integrative taxonomic work.

  18. Delineating spring recharge areas in a fractured sandstone aquifer (Luxembourg) based on pesticide mass balance

    Science.gov (United States)

    Farlin, J.; Drouet, L.; Gallé, T.; Pittois, D.; Bayerle, M.; Braun, C.; Maloszewski, P.; Vanderborght, J.; Elsner, M.; Kies, A.

    2013-06-01

    A simple method to delineate the recharge areas of a series of springs draining a fractured aquifer is presented. Instead of solving the flow and transport equations, the delineation is reformulated as a mass balance problem assigning arable land in proportion to the pesticide mass discharged annually in a spring at minimum total transport cost. The approach was applied to the Luxembourg Sandstone, a fractured-rock aquifer supplying half of the drinking water for Luxembourg, using the herbicide atrazine. Predictions of the recharge areas were most robust in situations of strong competition by neighbouring springs while the catchment boundaries for isolated springs were extremely sensitive to the parameter controlling flow direction. Validation using a different pesticide showed the best agreement with the simplest model used, whereas using historical crop-rotation data and spatially distributed soil-leaching data did not improve predictions. The whole approach presents the advantage of integrating objectively information on land use and pesticide concentration in spring water into the delineation of groundwater recharge zones in a fractured-rock aquifer.

  19. Historical Delineation of Landscape Units Using Physical Geographic Characteristics and Land Use/Cover Change

    Science.gov (United States)

    Campos-Campos, Oswaldo; Cruz-Cárdenas, Gustavo; Aquino, Roque Juan Carrasco; Moncayo-Estrada, Rodrigo; Machuca, Martha Alicia Velázquez; Meléndez, Luis Arturo Ávila

    2018-03-01

    Landscape units are conceived as a part of the territory that share similar physical and geographic characteristics. Their delineation can contribute to identify the physical and social dynamics that emerge in the spatial environment and to propose strategies of planning and management of the territory. The main objective was to make a historical delineation of landscape units in the Duero river basin that demonstrate the dynamics of changes in the territory, the description of the actors involved, and the affectations in the natural and social environment. We analyzed the vegetation change and urban growth from 1983 to 2014, incorporating climatic, edaphic, and topographic variables. A Principal Component Analysis was performed with the information and results were used in Maximum Likelihood procedure to define different clusters based on environmental characteristics. We defined five categories from the Landsat images. Results showed landscape units with homogeneous environmental characteristics and some differences in the units' delineation were mainly influenced by political and socioeconomic factors. Temporally there was an increased tendency of landscape units, three in 1983, nine in 1990, 1995, 2000 and 2011, and eight in 2014. This increase resulted from territory fragmentation because of berries and avocado cultivars expansion over wooded area.

  20. Detection of dead standing Eucalyptus camaldulensis without tree delineation for managing biodiversity in native Australian forest

    Science.gov (United States)

    Miltiadou, Milto; Campbell, Neil D. F.; Gonzalez Aracil, Susana; Brown, Tony; Grant, Michael G.

    2018-05-01

    In Australia, many birds and arboreal animals use hollows for shelters, but studies predict shortage of hollows in near future. Aged dead trees are more likely to contain hollows and therefore automated detection of them plays a substantial role in preserving biodiversity and consequently maintaining a resilient ecosystem. For this purpose full-waveform LiDAR data were acquired from a native Eucalypt forest in Southern Australia. The structure of the forest significantly varies in terms of tree density, age and height. Additionally, Eucalyptus camaldulensis have multiple trunk splits making tree delineation very challenging. For that reason, this paper investigates automated detection of dead standing Eucalyptus camaldulensis without tree delineation. It also presents the new feature of the open source software DASOS, which extracts features for 3D object detection in voxelised FW LiDAR. A random forest classifier, a weighted-distance KNN algorithm and a seed growth algorithm are used to create a 2D probabilistic field and to then predict potential positions of dead trees. It is shown that tree health assessment is possible without tree delineation but since it is a new research directions there are many improvements to be made.

  1. Historical Delineation of Landscape Units Using Physical Geographic Characteristics and Land Use/Cover Change

    Directory of Open Access Journals (Sweden)

    Campos-Campos Oswaldo

    2018-03-01

    Full Text Available Landscape units are conceived as a part of the territory that share similar physical and geographic characteristics. Their delineation can contribute to identify the physical and social dynamics that emerge in the spatial environment and to propose strategies of planning and management of the territory. The main objective was to make a historical delineation of landscape units in the Duero river basin that demonstrate the dynamics of changes in the territory, the description of the actors involved, and the affectations in the natural and social environment. We analyzed the vegetation change and urban growth from 1983 to 2014, incorporating climatic, edaphic, and topographic variables. A Principal Component Analysis was performed with the information and results were used in Maximum Likelihood procedure to define different clusters based on environmental characteristics. We defined five categories from the Landsat images. Results showed landscape units with homogeneous environmental characteristics and some differences in the units’ delineation were mainly influenced by political and socioeconomic factors. Temporally there was an increased tendency of landscape units, three in 1983, nine in 1990, 1995, 2000 and 2011, and eight in 2014. This increase resulted from territory fragmentation because of berries and avocado cultivars expansion over wooded area.

  2. A local contrast based approach to threshold segmentation for PET target volume delineation

    International Nuclear Information System (INIS)

    Drever, Laura; Robinson, Don M.; McEwan, Alexander; Roa, Wilson

    2006-01-01

    Current radiation therapy techniques, such as intensity modulated radiation therapy and three-dimensional conformal radiotherapy rely on the precise delivery of high doses of radiation to well-defined volumes. CT, the imaging modality that is most commonly used to determine treatment volumes cannot, however, easily distinguish between cancerous and normal tissue. The ability of positron emission tomography (PET) to more readily differentiate between malignant and healthy tissues has generated great interest in using PET images to delineate target volumes for radiation treatment planning. At present the accurate geometric delineation of tumor volumes is a subject open to considerable interpretation. The possibility of using a local contrast based approach to threshold segmentation to accurately delineate PET target cross sections is investigated using well-defined cylindrical and spherical volumes. Contrast levels which yield correct volumetric quantification are found to be a function of the activity concentration ratio between target and background, target size, and slice location. Possibilities for clinical implementation are explored along with the limits posed by this form of segmentation

  3. Methods for Delineating Degraded Land at Citarum Watershed, West Java, Indonesia

    Directory of Open Access Journals (Sweden)

    Suria Darma Tarigan

    2012-09-01

    Full Text Available Accurate information on the extent and spatial location of degraded lands is very important to plan their rehabilitation.So far, various institutions issue different estimation on the extent of degraded land in Indonesia led to big confusion for rehabilitation planning. Ministry of Forestry estimates around 30.2 million ha of degraded land both inside and outside forestry area throughout Indonesia based on data released in 2007. Ministry of Forestry implementes the socalled scoring method in delineating degraded land. Criteria used in the scoring methods are: land cover, slope steepness, erosion, and management. Scoring method applies different weight to each of those criteria. This study aimed to analyze accuracy of scoring method and to compare it to propose alternative methods in delineating degraded land such as: a Inconsistency of land use, and b Combination of Inconsistency of land use and scoring method. The accuracy of these methods were obtained by comparing to the field observation. The slope map was derived from SRTM 30 m, soil map was obtained from Soil Research Institute and land cover/land use from Ministry for Environment. Using GIS analysis, those maps were used to compose land capability classification (LCC and inconsistency of land use. The study showed that scoring method had 66% accuracy in delineating degraded land. When scoring method was combined with Inconsistency method the accuracy increased about 7%.

  4. Postoperative radiotherapy for glioma: improved delineation of the clinical target volume using the geodesic distance calculation.

    Directory of Open Access Journals (Sweden)

    DanFang Yan

    Full Text Available OBJECTS: To introduce a new method for generating the clinical target volume (CTV from gross tumor volume (GTV using the geodesic distance calculation for glioma. METHODS: One glioblastoma patient was enrolled. The GTV and natural barriers were contoured on each slice of the computer tomography (CT simulation images. Then, a graphic processing unit based on a parallel Euclidean distance transform was used to generate the CTV considering natural barriers. Three-dimensional (3D visualization technique was applied to show the delineation results. Speed of operation and precision were compared between this new delineation method and the traditional method. RESULTS: In considering spatial barriers, the shortest distance from the point sheltered from these barriers equals the sum of the distance along the shortest path between the two points; this consists of several segments and evades the spatial barriers, rather than being the direct Euclidean distance between two points. The CTV was generated irregularly rather than as a spherical shape. The time required to generate the CTV was greatly reduced. Moreover, this new method improved inter- and intra-observer variability in defining the CTV. CONCLUSIONS: Compared with the traditional CTV delineation, this new method using geodesic distance calculation not only greatly shortens the time to modify the CTV, but also has better reproducibility.

  5. Tumor bed delineation for external beam accelerated partial breast irradiation: A systematic review

    International Nuclear Information System (INIS)

    Yang, T. Jonathan; Tao, Randa; Elkhuizen, Paula H.M.; Vliet-Vroegindeweij, Corine van; Li, Guang; Powell, Simon N.

    2013-01-01

    In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1–2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer’s ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed

  6. Target Volume Delineation in Oropharyngeal Cancer: Impact of PET, MRI, and Physical Examination

    International Nuclear Information System (INIS)

    Thiagarajan, Anuradha; Caria, Nicola; Schöder, Heiko; Iyer, N. Gopalakrishna; Wolden, Suzanne; Wong, Richard J.; Sherman, Eric; Fury, Matthew G.; Lee, Nancy

    2012-01-01

    Introduction: Sole utilization of computed tomography (CT) scans in gross tumor volume (GTV) delineation for head-and-neck cancers is subject to inaccuracies. This study aims to evaluate contributions of magnetic resonance imaging (MRI), positron emission tomography (PET), and physical examination (PE) to GTV delineation in oropharyngeal cancer (OPC). Methods: Forty-one patients with OPC were studied. All underwent contrast-enhanced CT simulation scans (CECTs) that were registered with pretreatment PETs and MRIs. For each patient, three sets of primary and nodal GTV were contoured. First, reference GTVs (GTVref) were contoured by the treating radiation oncologist (RO) using CT, MRI, PET, and PE findings. Additional GTVs were created using fused CT/PET scans (GTVctpet) and CT/MRI scans (GTVctmr) by two other ROs blinded to GTVref. To compare GTVs, concordance indices (CI) were calculated by dividing the respective overlap volumes by overall volumes. To evaluate the contribution of PE, composite GTVs derived from CT, MRI, and PET (GTVctpetmr) were compared with GTVref. Results: For primary tumors, GTVref was significantly larger than GTVctpet and GTVctmr (p 0.75), indicating that although the modalities were complementary, the added benefit was small in the context of CECTs. In addition, PE did not aid greatly in nodal GTV delineation. Conclusion: PET and MRI are complementary and combined use is ideal. However, the low CI (ctpetmr vs. ref) particularly for primary tumors underscores the limitations of defining GTVs using imaging alone. PE is invaluable and must be incorporated.

  7. Music and Alterity Processes

    Directory of Open Access Journals (Sweden)

    Josep Martí

    2014-10-01

    Full Text Available The concept of alterity constitutes an important issue in anthropological research and, therefore, in the study of musical practices, as well. Without it, we could hardly understand other kinds of music situated in different spaces and time from the observer. In order to effectively approach these musical practices, we have to develop strategies to help us reduce as much as possible that which distorts the vision of the other. However, beyond the strictly epistemological and methodological issues, the study of music cannot ignore the ethical question related to the manner in which Western thought has understood and treated the other: through a hierarchical and stereotypical type of thinking based on the condition of otherness. Throughout the article, different alterity procedures are presented and discussed, such as synecdochization, exoticization, undervaluation, overvaluation, misunderstanding and exclusion. Taking these different alterity strategies into account may help us to better understand how the musical other is constructed, used and ultimately instrumentalized.

  8. Radio-anatomy Atlas for delineation SIRIADE web site: features and 1 year results; Site de radio-anatomie et d'aide a la delineation (SIRIADE): presentation et bilan a un an

    Energy Technology Data Exchange (ETDEWEB)

    Denisa, F. [Centre Jean-Bernard, Clinique Victor-Hugo, 72 - Le Mans (France); Pointreau, Y. [Clinique d' oncologie radiotherapie, Centre Henry-S.-Kaplan, CHU Bretonneau, 37 - Tours (France)

    2010-07-01

    3-D conformal radiotherapy is based on accurate target volumes delineation. Radio-anatomy knowledge's are useful but sometimes difficult to obtain. Moreover, the sources of recommendations for volume definition are disparate. We thus developed a free radio-anatomy web site dedicated to volumes delineation for radiation-oncologists (www.siriade.org). This web site is a search engine allowing to access to delineation characteristics of main tumours illustrated with clinical cases. It does not aim to provide guidelines. Its main purpose is to provide an iconographic training support with frequent up-datings. We present the features of this web site and one year connexion statistics. (authors)

  9. Multispecies genetic objectives in spatial conservation planning.

    Science.gov (United States)

    Nielsen, Erica S; Beger, Maria; Henriques, Romina; Selkoe, Kimberly A; von der Heyden, Sophie

    2017-08-01

    Growing threats to biodiversity and global alteration of habitats and species distributions make it increasingly necessary to consider evolutionary patterns in conservation decision making. Yet, there is no clear-cut guidance on how genetic features can be incorporated into conservation-planning processes, despite multiple molecular markers and several genetic metrics for each marker type to choose from. Genetic patterns differ between species, but the potential tradeoffs among genetic objectives for multiple species in conservation planning are currently understudied. We compared spatial conservation prioritizations derived from 2 metrics of genetic diversity (nucleotide and haplotype diversity) and 2 metrics of genetic isolation (private haplotypes and local genetic differentiation) in mitochondrial DNA of 5 marine species. We compared outcomes of conservation plans based only on habitat representation with plans based on genetic data and habitat representation. Fewer priority areas were selected for conservation plans based solely on habitat representation than on plans that included habitat and genetic data. All 4 genetic metrics selected approximately similar conservation-priority areas, which is likely a result of prioritizing genetic patterns across a genetically diverse array of species. Largely, our results suggest that multispecies genetic conservation objectives are vital to creating protected-area networks that appropriately preserve community-level evolutionary patterns. © 2016 Society for Conservation Biology.

  10. Differences in delineation guidelines for head and neck cancer result in inconsistent reported dose and corresponding NTCP

    International Nuclear Information System (INIS)

    Brouwer, Charlotte L.; Steenbakkers, Roel J.H.M.; Gort, Elske; Kamphuis, Marije E.; Laan, Hans Paul van der; Veld, Aart A. van’t; Sijtsema, Nanna M.; Langendijk, Johannes A.

    2014-01-01

    Purpose: To test the hypothesis that delineation of swallowing organs at risk (SWOARs) based on different guidelines results in differences in dose–volume parameters and subsequent normal tissue complication probability (NTCP) values for dysphagia-related endpoints. Materials and methods: Nine different SWOARs were delineated according to five different delineation guidelines in 29 patients. Reference delineation was performed according to the guidelines and NTCP-models of Christianen et al. Concordance Index (CI), dosimetric consequences, as well as differences in the subsequent NTCPs were calculated. Results: The median CI of the different delineation guidelines with the reference guidelines was 0.54 for the pharyngeal constrictor muscles, 0.56 for the laryngeal structures and 0.07 for the cricopharyngeal muscle and esophageal inlet muscle. The average difference in mean dose to the SWOARs between the guidelines with the largest difference (maxΔD) was 3.5 ± 3.2 Gy. A mean ΔNTCP of 2.3 ± 2.7% was found. For two patients, ΔNTCP exceeded 10%. Conclusions: The majority of the patients showed little differences in NTCPs between the different delineation guidelines. However, large NTCP differences >10% were found in 7% of the patients. For correct use of NTCP models in individual patients, uniform delineation guidelines are of great importance

  11. Automatic delineation of functional lung volumes with 68Ga-ventilation/perfusion PET/CT.

    Science.gov (United States)

    Le Roux, Pierre-Yves; Siva, Shankar; Callahan, Jason; Claudic, Yannis; Bourhis, David; Steinfort, Daniel P; Hicks, Rodney J; Hofman, Michael S

    2017-10-10

    Functional volumes computed from 68 Ga-ventilation/perfusion (V/Q) PET/CT, which we have shown to correlate with pulmonary function test parameters (PFTs), have potential diagnostic utility in a variety of clinical applications, including radiotherapy planning. An automatic segmentation method would facilitate delineation of such volumes. The aim of this study was to develop an automated threshold-based approach to delineate functional volumes that best correlates with manual delineation. Thirty lung cancer patients undergoing both V/Q PET/CT and PFTs were analyzed. Images were acquired following inhalation of Galligas and, subsequently, intravenous administration of 68 Ga-macroaggreted-albumin (MAA). Using visually defined manual contours as the reference standard, various cutoff values, expressed as a percentage of the maximal pixel value, were applied. The average volume difference and Dice similarity coefficient (DSC) were calculated, measuring the similarity of the automatic segmentation and the reference standard. Pearson's correlation was also calculated to compare automated volumes with manual volumes, and automated volumes optimized to PFT indices. For ventilation volumes, mean volume difference was lowest (- 0.4%) using a 15%max threshold with Pearson's coefficient of 0.71. Applying this cutoff, median DSC was 0.93 (0.87-0.95). Nevertheless, limits of agreement in volume differences were large (- 31.0 and 30.2%) with differences ranging from - 40.4 to + 33.0%. For perfusion volumes, mean volume difference was lowest and Pearson's coefficient was highest using a 15%max threshold (3.3% and 0.81, respectively). Applying this cutoff, median DSC was 0.93 (0.88-0.93). Nevertheless, limits of agreement were again large (- 21.1 and 27.8%) with volume differences ranging from - 18.6 to + 35.5%. Using the 15%max threshold, moderate correlation was demonstrated with FEV1/FVC (r = 0.48 and r = 0.46 for ventilation and perfusion images, respectively

  12. A generalized methodology for identification of threshold for HRU delineation in SWAT model

    Science.gov (United States)

    M, J.; Sudheer, K.; Chaubey, I.; Raj, C.

    2016-12-01

    The distributed hydrological model, Soil and Water Assessment Tool (SWAT) is a comprehensive hydrologic model widely used for making various decisions. The simulation accuracy of the distributed hydrological model differs due to the mechanism involved in the subdivision of the watershed. Soil and Water Assessment Tool (SWAT) considers sub-dividing the watershed and the sub-basins into small computing units known as 'hydrologic response units (HRU). The delineation of HRU is done based on unique combinations of land use, soil types, and slope within the sub-watersheds, which are not spatially defined. The computations in SWAT are done at HRU level and are then aggregated up to the sub-basin outlet, which is routed through the stream system. Generally, the HRUs are delineated by considering a threshold percentage of land use, soil and slope are to be given by the modeler to decrease the computation time of the model. The thresholds constrain the minimum area for constructing an HRU. In the current HRU delineation practice in SWAT, the land use, soil and slope of the watershed within a sub-basin, which is less than the predefined threshold, will be surpassed by the dominating land use, soil and slope, and introduce some level of ambiguity in the process simulations in terms of inappropriate representation of the area. But the loss of information due to variation in the threshold values depends highly on the purpose of the study. Therefore this research studies the effects of threshold values of HRU delineation on the hydrological modeling of SWAT on sediment simulations and suggests guidelines for selecting the appropriate threshold values considering the sediment simulation accuracy. The preliminary study was done on Illinois watershed by assigning different thresholds for land use and soil. A general methodology was proposed for identifying an appropriate threshold for HRU delineation in SWAT model that considered computational time and accuracy of the simulation

  13. Using aquatic invertebrates to delineate seasonal and temporary wetlands in the Prairie Pothole Region of North America

    Science.gov (United States)

    Euliss, Ned H.; Mushet, David M.; Johnson, Douglas H.

    2002-01-01

    Tillage can destroy or greatly disturb indicators of hydric soils and hydrophytic vegetation, making delineation of tilled wetlands difficult. The remains of aquatic invertebrates (e.g., shells, drought-resistant eggs, and trichopteran cases) are easily identifiable and persist in wetland substrates even when wetlands are dry. Additionally, these remains are not easily destroyed by mechanical tillage. To test the feasibility of using invertebrate remains to delineate wetlands, we used two methods to identify the wetland edge of ten seasonal and ten temporary wetlands, evenly divided between grassland and cropland landscapes. First, we identified the wetland edge using hydric soil and vegetation indicators along six evenly spaced transects in each wetland (our “standard” delineation). We then identified the wetland edge along the same transects using aquatic invertebrate remains as our indicator. In grassland landscapes, delineations of the wetland edge made using invertebrate remains were consistently at the same location or closer to the wetland center as the standard delineations for both seasonal and temporary wetlands. In cropland landscapes, however, many of our invertebrate delineations of seasonal and temporary wetlands were on the upland side of our standard delineations. We attribute the differences to movement of remains during tillage, increased maximum pool levels in cropland wetlands, and disturbance of hydric soils and plants. We found that the elevations of the wetland edge indicated by invertebrate remains were more consistent within a wetland than elevations determined by standard delineations. Aquatic invertebrate remains can be useful in delineating wetlands when other indicators have been destroyed or severely disturbed by tillage.

  14. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters

    Science.gov (United States)

    Wu, Minhao; Dong, Bin; Cao, Aiqin; Li, Hai; Liu, Jingwen

    2015-01-01

    Background PCSK9 has emerged as a key regulator of serum LDL-C metabolism by promoting the degradation of hepatic LDL receptor (LDLR). In this study, we investigated the effect of fasting on serum PCSK9, LDL-C, and hepatic LDLR expression in hamsters and further delineated the molecular pathways involved in fasting-induced repression of PCSK9 transcription. Results Fasting had insignificant effects on serum total cholesterol and HDL-C levels, but reduced LDL-C, triglyceride and insulin levels. The decrease in serum LDL-C was accompanied by marked reductions of hepatic PCSK9 mRNA and serum PCSK9 protein levels with concomitant increases of hepatic LDLR protein amounts. Fasting produced a profound impact on SREBP1 expression and its transactivating activity, while having modest effects on mRNA expressions of SREBP2 target genes in hamster liver. Although PPARα mRNA levels in hamster liver were elevated by fasting, ligand-induced activation of PPARα with WY14643 compound in hamster primary hepatocytes did not affect PCSK9 mRNA or protein expressions. Further investigation on HNF1α, a critical transactivator of PCSK9, revealed that fasting did not alter its mRNA expression, however, the protein abundance of HNF1α in nuclear extracts of hamster liver was markedly reduced by prolonged fasting. Conclusion Fasting lowered serum LDL-C in hamsters by increasing hepatic LDLR protein amounts via reductions of serum PCSK9 levels. Importantly, our results suggest that attenuation of SREBP1 transactivating activity owing to decreased insulin levels during fasting is primarily responsible for compromised PCSK9 gene transcription, which was further suppressed after prolonged fasting by a reduction of nuclear HNF1α protein abundance. PMID:22954675

  15. Delineation of spall zone from pre/post shot reflections studies: Preliminary results from BEXAR. Los Alamos Source Region Project

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S.R.; Cogbill, A.H.; Weaver, T.A. [Los Alamos National Lab., NM (United States); Miller, R.; Steeples, D. [Kansas Univ., Lawrence, KS (United States)

    1992-12-31

    In order to delineate the lateral and depth extent of spall from a buried nuclear explosion, we have performed a high-resolution pre- and post-shot seismic reflection survey from BEXAR. Although the data quality were marginal due to poor wave propagation through the volcanic tuffs of Pahute Mesa, a number of interesting differences are observed on the pre- and post-shot surveys. On the pre-shot survey, a reflector (reflector `` 1 ``) is observed at 250 ms (or about 150 m depth) using a stacking velocity of 1300 m/s. On the post-shot survey two reflectors are observed and a stacking velocity of 1150 m/s was used representing a 12% reduction in compressional velocity. With this stacking velocity, reflector `` 1 `` is recorded at 290 ms (still at about 150 m depth) and a new reflector ``2`` is observed at 210 ms (or about 100 m depth). These stacking velocities correspond well with available uphole travel times collected in U19ba and nearby U19ax (BEXAR and KEARSARGE emplacement holes, respectively). The cause for the differences observed in the pre- and post-shot surveys may be due to one of two reasons. First, it is possible that the near-surface rocks were damaged as part of the spallation process (thus reducing the in situ velocities) and reflector ``2`` represents a spall detachment surface. However, analysis of acceleration data collected close to the reflection line suggests that the ground motions were probably inadequate to damage the tuffs. Also, no evidence of actual spallation was actually observed. The second hypothesis is that the near-surface velocities of the tuffs were altered by the change in saturation state due to extensive rains occurring between the pre- and postshot surveys. Although the dependence of seismic velocity on saturation state is controlled by a number of complex factors, it cannot be ruled out.

  16. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  17. Alterações genéticas no cancro do pulmão: Avaliação das limitações ao seu uso na rotina clínica Genetic alterations in lung cancer: Assessing limitations in routine clinical use

    Directory of Open Access Journals (Sweden)

    Joana Espiga Macedo

    2007-01-01

    Full Text Available O cancro do pulmão é a causa mais frequente de mortalidade por cancro no mundo, sendo responsável por cerca de 1,1 milhões de mortes por ano. A sobrevivência média dos doentes é geralmente curta, por a doença se encontrar em estádios avançados na altura do diagnóstico, mas também devido à falta de eficácia dos tratamentos disponíveis. O advento da genética molecular dos tumores trouxe consigo a possibilidade de modificar esta situação, quer através do refinamento do diagnóstico, quer da identificação de alvos terapêuticos específicos, quer sobretudo por - pelo menos em teoria - permitir o diagnóstico precoce da doença. No entanto, e apesar de numerosos trabalhos terem já demonstrado a utilidade das técnicas da genética molecular no estudo do cancro do pulmão, o seu uso na rotina clínica em Portugal tem sido limitado. No presente estudo, utilizou-se a pesquisa de mutações no anti-oncogene p53 em amostras clínicas de doentes com diagnóstico de cancro do pulmão como método para identificar as dificuldades práticas à integração da genética molecular na rotina clínica. Os resultados obtidos sugerem que o principal factor limitante a essa integração é a obtenção de amostras de ADN de qualidade, um problema que pode ser superado pela alteração das práticas correntes de recolha de amostras.Lung cancer is the most frequent cause of cancer mortality worldwide, responsible for approximately 1.1 million deaths per year. Median survival is short, both as most tumours are diagnosed at an advanced stage and because of the limited efficacy of available treatments. The development of tumour molecular genetics carries the promise of altering this state of affairs, as it should lead to a more precise classification of tumours, identify specific molecular targets for therapy and, above all, allow the development of new methods for early diagnosis. Despite numerous studies demonstrating the usefulness of molecular

  18. The Pleurobemini (Bivalvia: Unionida) revisited: Molecular species delineation using a mitochondrial DNA gene reveals multiple conspecifics and undescribed species

    Science.gov (United States)

    Inoue, Kentaro; Hayes, David M.; Harris, John L.; Johnson, Nathan A.; Morrison, Cheryl L.; Eackles, Michael S.; King, Tim; Jones, Jess W.; Hallerman, Eric M.; Christian, Alan D.; Randklev, Charles R.

    2018-01-01

    The Pleurobemini (Bivalvia: Unionida) represent approximately one-third of freshwater mussel diversity in North America. Species identification within this group is challenging due to morphological convergence and phenotypic plasticity. Accurate species identification, including characterisation of currently unrecognised taxa, is required to develop effective conservation strategies because many species in the group are imperiled. We examined 575 cox1 sequences from 110 currently recognised species (including 13 Fusconaia and 21 Pleurobema species) to understand phylogenetic relationships among pleurobemine species (mainly Fusconaia and Pleurobema) and to delineate species boundaries. The results of phylogenetic analyses showed no geographic structure within widespread species and illustrated a close relationship between Elliptio lanceolata and Parvaspina collina. Constraint tests supported monophyly of the genera Fusconaia and Pleurobema, including the subgenus P. (Sintoxia). Furthermore, results revealed multiple conspecifics, including P. hanleyianum and P. troschelianum, P. chattanoogaense and P. decisum, P. clava and P. oviforme, P. rubrum and P. sintoxia, F. askewi and F. lananensis, and F. cerina and F. flava. Species delimitation analyses identified three currently unrecognised taxa (two in Fusconaia and one in Pleurobema). Further investigation using additional genetic markers and other lines of evidence (e.g. morphology, life history, ecology) are necessary before any taxonomic changes are formalised.

  19. Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

    Science.gov (United States)

    Iftimia, Nicusor; Peterson, Gary; Chang, Ernest W.; Maguluri, Gopi; Fox, William; Rajadhyaksha, Milind

    2016-01-01

    We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ˜1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ˜7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ˜600 μm, and agreement with histology was within about ±50 μm.

  20. Evolutionary genetics

    National Research Council Canada - National Science Library

    Maynard Smith, John

    1989-01-01

    .... It differs from other textbooks of population genetics in applying the basic theory to topics, such as social behaviour, molecular evolution, reiterated DNA, and sex, which are the main subjects...

  1. Genetic Discrimination

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  2. Arthropod Genetics.

    Science.gov (United States)

    Zumwalde, Sharon

    2000-01-01

    Introduces an activity on arthropod genetics that involves phenotype and genotype identification of the creature and the construction process. Includes a list of required materials and directions to build a model arthropod. (YDS)

  3. Desktop Genetics

    OpenAIRE

    Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

    2016-01-01

    Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learni...

  4. Genetic and phenotypic intra-species variation in Candida albicans.

    Science.gov (United States)

    Hirakawa, Matthew P; Martinez, Diego A; Sakthikumar, Sharadha; Anderson, Matthew Z; Berlin, Aaron; Gujja, Sharvari; Zeng, Qiandong; Zisson, Ethan; Wang, Joshua M; Greenberg, Joshua M; Berman, Judith; Bennett, Richard J; Cuomo, Christina A

    2015-03-01

    Candida albicans is a commensal fungus of the human gastrointestinal tract and a prevalent opportunistic pathogen. To examine diversity within this species, extensive genomic and phenotypic analyses were performed on 21 clinical C. albicans isolates. Genomic variation was evident in the form of polymorphisms, copy number variations, chromosomal inversions, subtelomeric hypervariation, loss of heterozygosity (LOH), and whole or partial chromosome aneuploidies. All 21 strains were diploid, although karyotypic changes were present in eight of the 21 isolates, with multiple strains being trisomic for Chromosome 4 or Chromosome 7. Aneuploid strains exhibited a general fitness defect relative to euploid strains when grown under replete conditions. All strains were also heterozygous, yet multiple, distinct LOH tracts were present in each isolate. Higher overall levels of genome heterozygosity correlated with faster growth rates, consistent with increased overall fitness. Genes with the highest rates of amino acid substitutions included many cell wall proteins, implicating fast evolving changes in cell adhesion and host interactions. One clinical isolate, P94015, presented several striking properties including a novel cellular phenotype, an inability to filament, drug resistance, and decreased virulence. Several of these properties were shown to be due to a homozygous nonsense mutation in the EFG1 gene. Furthermore, loss of EFG1 function resulted in increased fitness of P94015 in a commensal model of infection. Our analysis therefore reveals intra-species genetic and phenotypic differences in C. albicans and delineates a natural mutation that alters the balance between commensalism and pathogenicity. © 2015 Hirakawa et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Mapping advanced argillic alteration at Cuprite, Nevada, using imaging spectroscopy

    Science.gov (United States)

    Swayze, Gregg A.; Clark, Roger N.; Goetz, Alexander F.H.; Livo, K. Eric; Breit, George N.; Kruse, Fred A.; Sutley, Stephen J.; Snee, Lawrence W.; Lowers, Heather A.; Post, James L.; Stoffregen, Roger E.; Ashley, Roger P.

    2014-01-01

    Mineral maps based on Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data were used to study late Miocene advanced argillic alteration at Cuprite, Nevada. Distributions of Fe-bearing minerals, clays, micas, sulfates, and carbonates were mapped using the Tetracorder spectral-shape matching system. The Al content of white micas increases toward altered areas and near intrusive rocks. Alunite composition varies from pure K to intimate mixtures of Na-K endmembers with subpixel occurrences of huangite, the Ca analogue of alunite. Intimately mixed Na-K alunite marks areas of relatively lower alteration temperature, whereas co-occurring Na-alunite and dickite may delineate relict hydrothermal conduits. The presence of dickite, halloysite, and well-ordered kaolinite, but absence of disordered kaolinite, is consistent with acidic conditions during hydrothermal alteration. Partial lichen cover on opal spectrally mimics chalcedony, limiting its detection to lichen-free areas. Pods of buddingtonite are remnants of initial quartz-adularia-smectite alteration. Thus, spectral maps provide a synoptic view of the surface mineralogy, and define a previously unrecognized early steam-heated hydrothermal event.Faulting and episodes of hydrothermal alteration at Cuprite were intimately linked to upper plate movements above the Silver Peak-Lone Mountain detachment and growth, collapse, and resurgence of the nearby Stonewall Mountain volcanic complex between 8 and 5 Ma. Isotopic dating indicates that hydrothermal activity started at least by 7.61 Ma and ended by about 6.2 Ma. Spectral and stable isotope data suggest that Cuprite is a late Miocene low-sulfidation adularia-sericite type hot spring deposit overprinted by late-stage, steam-heated advanced argillic alteration formed along the margin of the Stonewall Mountain caldera.

  6. Personality disorder traits, family environment, and alcohol misuse: a multivariate behavioural genetic analysis.

    Science.gov (United States)

    Jang, K L; Vernon, P A; Livesley, W J

    2000-06-01

    This study seeks to estimate the extent to which a common genetic and environmental basis is shared between (i) traits delineating specific aspects of antisocial personality and alcohol misuse, and (ii) childhood family environments, traits delineating broad domains of personality pathology and alcohol misuse. Postal survey data were collected from monozygotic and dizygotic twin pairs. Twin pairs were recruited from Vancouver, British Columbia and London, Ontario, Canada using newspaper advertisements, media stories and twin clubs. Data obtained from 324 monozygotic and 335 dizygotic twin pairs were used to estimate the extent to which traits delineating specific antisocial personality traits and alcohol misuse shared a common genetic and environmental aetiology. Data from 81 monozygotic and 74 dizygotic twin pairs were used to estimate the degree to which traits delineating personality pathology, childhood family environment and alcohol misuse shared a common aetiology. Current alcohol misuse and personality pathology were measured using scales contained in the self-report Dimensional Assessment of Personality Pathology. Perceptions of childhood family environment were measured using the self-report Family Environment Scale. Multivariate genetic analyses showed that a subset of traits delineating components of antisocial personality (i.e. grandiosity, attention-seeking, failure to adopt social norms, interpersonal violence and juvenile antisocial behaviours) are influenced by genetic factors in common to alcohol misuse. Genetically based perceptions of childhood family environment had little relationship with alcohol misuse. Heritable personality factors that influence the perception of childhood family environment play only a small role in the liability to alcohol misuse. Instead, liability to alcohol misuse is related to genetic factors common a specific subset of antisocial personality traits describing conduct problems, narcissistic and stimulus

  7. Evolution of Genetic Variance during Adaptive Radiation.

    Science.gov (United States)

    Walter, Greg M; Aguirre, J David; Blows, Mark W; Ortiz-Barrientos, Daniel

    2018-04-01

    Genetic correlations between traits can concentrate genetic variance into fewer phenotypic dimensions that can bias evolutionary trajectories along the axis of greatest genetic variance and away from optimal phenotypes, constraining the rate of evolution. If genetic correlations limit adaptation, rapid adaptive divergence between multiple contrasting environments may be difficult. However, if natural selection increases the frequency of rare alleles after colonization of new environments, an increase in genetic variance in the direction of selection can accelerate adaptive divergence. Here, we explored adaptive divergence of an Australian native wildflower by examining the alignment between divergence in phenotype mean and divergence in genetic variance among four contrasting ecotypes. We found divergence in mean multivariate phenotype along two major axes represented by different combinations of plant architecture and leaf traits. Ecotypes also showed divergence in the level of genetic variance in individual traits and the multivariate distribution of genetic variance among traits. Divergence in multivariate phenotypic mean aligned with divergence in genetic variance, with much of the divergence in phenotype among ecotypes associated with changes in trait combinations containing substantial levels of genetic variance. Overall, our results suggest that natural selection can alter the distribution of genetic variance underlying phenotypic traits, increasing the amount of genetic variance in the direction of natural selection and potentially facilitating rapid adaptive divergence during an adaptive radiation.

  8. J. Genet. classic 101

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 85, No. 2, August 2006. 101. Page 2. J. Genet. classic. 102. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 3. J. Genet. classic. Journal of Genetics, Vol. 85, No. 2, August 2006. 103. Page 4. J. Genet. classic. 104. Journal of Genetics, Vol. 85, No. 2, August 2006. Page 5. J. Genet. classic.

  9. J. Genet. classic 37

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 84, No. 1, April 2005. 37. Page 2. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 38. Page 3. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 39. Page 4. J. Genet. classic. Journal of Genetics, Vol. 84, No. 1, April 2005. 40. Page 5. J. Genet. classic. Journal of ...

  10. Thymic Stromal Alterations and Genetic Disorders of Immune System

    OpenAIRE

    Pignata, Claudio; D?Assante, Roberta; Sousa, Ana E.

    2015-01-01

    © 2015 Pignata, D’Assante and Sousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

  11. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery

  12. A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space

    Data.gov (United States)

    National Aeronautics and Space Administration — Bacterial behavior has been observed to change during spaceflight. Higher final cell counts enhanced biofilm formation increased virulence and reduced susceptibility...

  13. Looping Genomes: Diagnostic Change and the Genetic Makeup of the Autism Population.

    Science.gov (United States)

    Navon, Daniel; Eyal, Gil

    2016-03-01

    This article builds on Hacking's framework of "dynamic nominalism" to show how knowledge about biological etiology can interact with the "kinds of people" delineated by diagnostic categories in ways that "loop" or modify both over time. The authors use historical materials to show how "geneticization" played a crucial role in binding together autism as a biosocial community and how evidence from genetics research later made an important contribution to the diagnostic expansion of autism. In the second part of the article, the authors draw on quantitative and qualitative analyses of autism rates over time in several rare conditions that are delineated strictly according to genomic mutations in order to demonstrate that these changes in diagnostic practice helped to both increase autism's prevalence and create its enormous genetic heterogeneity. Thus, a looping process that began with geneticization and involved the social effects of genetics research itself transformed the autism population and its genetic makeup.

  14. Characteristics and landcover of estuarine boundaries: implications for the delineation of the South African estuarine functional zone

    CSIR Research Space (South Africa)

    Veldkornet, DA

    2015-11-01

    Full Text Available Zulu-Natal), cultivation has removed estuarine habitat. Although delineation of boundaries can be complicated by landcover changes, the estuarine lateral boundary in Cape estuaries could be identified based on sediment characteristics (moisture content, organic content...

  15. A novel algorithm for delineating wetland depressions and mapping surface hydrologic flow pathways using LiDAR data

    Science.gov (United States)

    In traditional watershed delineation and topographic modeling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM) to enforce flow continuity of water across the topographic surface to the watershed outlets. In re...

  16. Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study

    DEFF Research Database (Denmark)

    Nyholm, Tufve; Jonsson, Joakim; Söderström, Karin

    2013-01-01

    and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength. CONCLUSION: The overall......BACKGROUND: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work....... Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra- and inter-physician variability, and dependence between variability and origin of the MR images, i...

  17. PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

    NARCIS (Netherlands)

    Reijnders, Margot R. F.; Janowski, Robert; Alvi, Mohsan; Self, Jay E.; van Essen, Ton J.; Vreeburg, Maaike; Rouhl, Rob P. W.; Stevens, Servi J. C.; Stegmann, Alexander P. A.; Schieving, Jolanda; Pfundt, Rolph; van Dijk, Katinke; Smeets, Eric; Stumpel, Connie T. R. M.; Bok, Levinus A.; Cobben, Jan Maarten; Engelen, Marc; Mansour, Sahar; Whiteford, Margo; Chandler, Kate E.; Douzgou, Sofia; Cooper, Nicola S.; Tan, Ene-Choo; Foo, Roger; Lai, Angeline H. M.; Rankin, Julia; Green, Andrew; Lönnqvist, Tuula; Isohanni, Pirjo; Williams, Shelley; Ruhoy, Ilene; Carvalho, Karen S.; Dowling, James J.; Lev, Dorit L.; Sterbova, Katalin; Lassuthova, Petra; Neupauerová, Jana; Waugh, Jeff L.; Keros, Sotirios; Clayton-Smith, Jill; Smithson, Sarah F.; Brunner, Han G.; van Hoeckel, Ceciel; Anderson, Mel; Clowes, Virginia E.; Siu, Victoria Mok; Selber, Paulo; Leventer, Richard J.; Nellaker, Christoffer; Niessing, Dierk; Hunt, David; Baralle, Diana

    2018-01-01

    Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and

  18. Delineation of Nested Wetland Catchments and Modeling of Hydrologic Connectivity Using LiDAR Data and Aerial Imagery

    Science.gov (United States)

    In traditional watershed delineation and topographic modelling, surface depressions are generally treated as spurious features and simply removed from a digital elevation model (DEM) to enforce flow continuity of water across the topographic surface to the watershed outlets. In r...

  19. Estimating effective landscape distances and movement corridors: Comparison of habitat and genetic data

    Science.gov (United States)

    Maria C. Mateo-Sanchez; Niko Balkenhol; Samuel Cushman; Trinidad Perez; Ana Dominguez; Santiago Saura

    2015-01-01

    Resistance models provide a key foundation for landscape connectivity analyses and are widely used to delineate wildlife corridors. Currently, there is no general consensus regarding the most effective empirical methods to parameterize resistance models, but habitat data (species’ presence data and related habitat suitability models) and genetic data are the...

  20. Geomorphic Flood Area (GFA): a QGIS tool for a cost-effective delineation of the floodplains

    Science.gov (United States)

    Samela, Caterina; Albano, Raffaele; Sole, Aurelia; Manfreda, Salvatore

    2017-04-01

    The importance of delineating flood hazard and risk areas at a global scale has been highlighted for many years. However, its complete achievement regularly encounters practical difficulties, above all the lack of data and implementation costs. In conditions of scarce data availability (e.g. ungauged basins, large-scale analyses), a fast and cost-effective floodplain delineation can be carried out using geomorphic methods (e.g., Manfreda et al., 2011; 2014). In particular, an automatic DEM-based procedure has been implemented in an open-source QGIS plugin named Geomorphic Flood Area - tool (GFA - tool). This tool performs a linear binary classification based on the recently proposed Geomorphic Flood Index (GFI), which exhibited high classification accuracy and reliability in several test sites located in Europe, United States and Africa (Manfreda et al., 2015; Samela et al., 2016, 2017; Samela, 2016). The GFA - tool is designed to make available to all users the proposed procedure, that includes a number of operations requiring good geomorphic and GIS competences. It allows computing the GFI through terrain analysis, turning it into a binary classifier, and training it on the base of a standard inundation map derived for a portion of the river basin (a minimum of 2% of the river basin's area is suggested) using detailed methods of analysis (e.g. flood hazard maps produced by emergency management agencies or river basin authorities). Finally, GFA - tool allows to extend the classification outside the calibration area to delineate the flood-prone areas across the entire river basin. The full analysis has been implemented in this plugin with a user-friendly interface that should make it easy to all user to apply the approach and produce the desired results. Keywords: flood susceptibility; data scarce environments; geomorphic flood index; linear binary classification; Digital elevation models (DEMs). References Manfreda, S., Di Leo, M., Sole, A., (2011). Detection of

  1. Quantifying the performance of automated GIS-based geomorphological approaches for riparian zone delineation using digital elevation models

    OpenAIRE

    D. Fernández; J. Barquín; M. Álvarez-Cabria; F. J. Peñas

    2012-01-01

    Riparian zone delineation is a central issue for managing rivers and adjacent areas; however, criteria used to delineate them are still under debate. The area inundated by a 50-yr flood has been indicated as an optimal hydrological descriptor for riparian areas. This detailed hydrological information is usually only available for populated areas at risk of flooding. In this work we created several floodplain surfaces by means of two different GIS-based geomorphological appro...

  2. Genetics of uveal melanoma and cutaneous melanoma: two of a kind?

    NARCIS (Netherlands)

    T. van den Bosch (Thomas); E. Kiliç (Emine); A.D.A. Paridaens (Dion); J.E.M.M. de Klein (Annelies)

    2010-01-01

    textabstractCutaneous melanoma and uveal melanoma both derive from melanocytes but show remarkable differences in tumorigenesis, mode of metastatic spread, genetic alterations, and therapeutic response. In this review we discuss the differences and similarities along with the genetic research

  3. 76 FR 8707 - Syngenta Seeds, Inc.; Determination of Nonregulated Status for Corn Genetically Engineered To...

    Science.gov (United States)

    2011-02-15

    ... Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or Which There... genetic engineering that are plant pests or that there is reason to believe are plant pests. Such...

  4. Genetic Variation in Schizophrenia Liability is Shared With Intellectual Ability and Brain Structure

    NARCIS (Netherlands)

    Bohlken, Marc M; Brouwer, Rachel M; Mandl, René C W; Kahn, René S; Hulshoff Pol, Hilleke E

    2016-01-01

    BACKGROUND: Alterations in intellectual ability and brain structure are important genetic markers for schizophrenia liability. How variations in these phenotypes interact with variance in schizophrenia liability due to genetic or environmental factors is an area of active investigation. Studying

  5. LNAPL source zone delineation using soil gases in a heterogeneous silty-sand aquifer

    Science.gov (United States)

    Cohen, Grégory J. V.; Jousse, Florie; Luze, Nicolas; Höhener, Patrick; Atteia, Olivier

    2016-09-01

    Source delineation of hydrocarbon contaminated sites is of high importance for remediation work. However, traditional methods like soil core extraction and analysis or recent Membrane Interface Probe methods are time consuming and costly. Therefore, the development of an in situ method based on soil gas analysis can be interesting. This includes the direct measurement of volatile organic compounds (VOCs) in soil gas taken from gas probes using a PID (Photo Ionization Detector) and the analysis of other soil gases related to VOC degradation distribution (CH4, O2, CO2) or related to presence of Light Non-Aqueous Phase Liquid (LNAPL) as 222Rn. However, in widespread heterogeneous formations, delineation by gas measurements becomes more challenging. The objective of this study is twofold: (i) to analyse the potential of several in situ gas measurement techniques in comparison to soil coring for LNAPL source delineation at a heterogeneous contaminated site where the techniques might be limited by a low diffusion potential linked to the presence of fine sands and silts, and (ii) to analyse the effect of vertical sediment heterogeneities on the performance of these gas measurement methods. Thus, five types of gases were analysed: VOCs, their three related degradation products O2, CO2 and CH4 and 222Rn. Gas measurements were compared to independent LNAPL analysis by coring. This work was conducted at an old industrial site frequently contaminated by a Diesel-Fuel mixture located in a heterogeneous fine-grained aquifer. Results show that in such heterogeneous media migration of reactive gases like VOCs occurs only across small distances and the VOC concentrations sampled with gas probes are mainly related to local conditions rather than the presence of LNAPL below the gas probe. 222Rn is not well correlated with LNAPL because of sediment heterogeneity. Oxygen, CO2, and especially CH4, have larger lengths of diffusion and give the clearest picture for LNAPL presence at this

  6. Improvement in Interobserver Accuracy in Delineation of the Lumpectomy Cavity Using Fiducial Markers

    International Nuclear Information System (INIS)

    Shaikh, Talha; Chen Ting; Khan, Atif; Yue, Ning J.; Kearney, Thomas; Cohler, Alan; Haffty, Bruce G.; Goyal, Sharad

    2010-01-01

    Purpose: To determine, whether the presence of gold fiducial markers would improve the inter- and intraphysician accuracy in the delineation of the surgical cavity compared with a matched group of patients who did not receive gold fiducial markers in the setting of accelerated partial-breast irradiation (APBI). Methods and Materials: Planning CT images of 22 lumpectomy cavities were reviewed in a cohort of 22 patients; 11 patients received four to six gold fiducial markers placed at the time of surgery. Three physicians categorized the seroma cavity according to cavity visualization score criteria and delineated each of the 22 seroma cavities and the clinical target volume. Distance between centers of mass, percentage overlap, and average surface distance for all patients were assessed. Results: The mean seroma volume was 36.9 cm 3 and 34.2 cm 3 for fiducial patients and non-fiducial patients, respectively (p = ns). Fiducial markers improved the mean cavity visualization score, to 3.6 ± 1.0 from 2.5 ± 1.3 (p < 0.05). The mean distance between centers of mass, average surface distance, and percentage overlap for the seroma and clinical target volume were significantly improved in the fiducial marker patients as compared with the non-fiducial marker patients (p < 0.001). Conclusions: The placement of gold fiducial markers placed at the time of lumpectomy improves interphysician identification and delineation of the seroma cavity and clinical target volume. This has implications in radiotherapy treatment planning for accelerated partial-breast irradiation and for boost after whole-breast irradiation.

  7. Definition and delineation of the clinical target volume for rectal cancer

    International Nuclear Information System (INIS)

    Roels, Sarah; Duthoy, Wim; Haustermans, Karin; Penninckx, Freddy; Vandecaveye, Vincent; Boterberg, Tom; Neve, Wilfried de

    2006-01-01

    Purpose: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. Methods and Materials: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. Results: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. Conclusion: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV

  8. ACCURACY ASSESSMENT OF CROWN DELINEATION METHODS FOR THE INDIVIDUAL TREES USING LIDAR DATA

    Directory of Open Access Journals (Sweden)

    K. T. Chang

    2016-06-01

    Full Text Available Forest canopy density and height are used as variables in a number of environmental applications, including the estimation of biomass, forest extent and condition, and biodiversity. The airborne Light Detection and Ranging (LiDAR is very useful to estimate forest canopy parameters according to the generated canopy height models (CHMs. The purpose of this work is to introduce an algorithm to delineate crown parameters, e.g. tree height and crown radii based on the generated rasterized CHMs. And accuracy assessment for the extraction of volumetric parameters of a single tree is also performed via manual measurement using corresponding aerial photo pairs. A LiDAR dataset of a golf course acquired by Leica ALS70-HP is used in this study. Two algorithms, i.e. a traditional one with the subtraction of a digital elevation model (DEM from a digital surface model (DSM, and a pit-free approach are conducted to generate the CHMs firstly. Then two algorithms, a multilevel morphological active-contour (MMAC and a variable window filter (VWF, are implemented and used in this study for individual tree delineation. Finally, experimental results of two automatic estimation methods for individual trees can be evaluated with manually measured stand-level parameters, i.e. tree height and crown diameter. The resulting CHM generated by a simple subtraction is full of empty pixels (called "pits" that will give vital impact on subsequent analysis for individual tree delineation. The experimental results indicated that if more individual trees can be extracted, tree crown shape will became more completely in the CHM data after the pit-free process.

  9. Spatial and thematic assessment of object-based forest stand delineation using an OFA-matrix

    Science.gov (United States)

    Hernando, A.; Tiede, D.; Albrecht, F.; Lang, S.

    2012-10-01

    The delineation and classification of forest stands is a crucial aspect of forest management. Object-based image analysis (OBIA) can be used to produce detailed maps of forest stands from either orthophotos or very high resolution satellite imagery. However, measures are then required for evaluating and quantifying both the spatial and thematic accuracy of the OBIA output. In this paper we present an approach for delineating forest stands and a new Object Fate Analysis (OFA) matrix for accuracy assessment. A two-level object-based orthophoto analysis was first carried out to delineate stands on the Dehesa Boyal public land in central Spain (Avila Province). Two structural features were first created for use in class modelling, enabling good differentiation between stands: a relational tree cover cluster feature, and an arithmetic ratio shadow/tree feature. We then extended the OFA comparison approach with an OFA-matrix to enable concurrent validation of thematic and spatial accuracies. Its diagonal shows the proportion of spatial and thematic coincidence between a reference data and the corresponding classification. New parameters for Spatial Thematic Loyalty (STL), Spatial Thematic Loyalty Overall (STLOVERALL) and Maximal Interfering Object (MIO) are introduced to summarise the OFA-matrix accuracy assessment. A stands map generated by OBIA (classification data) was compared with a map of the same area produced from photo interpretation and field data (reference data). In our example the OFA-matrix results indicate good spatial and thematic accuracies (>65%) for all stand classes except for the shrub stands (31.8%), and a good STLOVERALL (69.8%). The OFA-matrix has therefore been shown to be a valid tool for OBIA accuracy assessment.

  10. Delineation of Rain Areas with TRMM Microwave Observations Based on PNN

    Directory of Open Access Journals (Sweden)

    Shiguang Xu

    2014-12-01

    Full Text Available False alarm and misdetected precipitation are prominent drawbacks of high-resolution satellite precipitation datasets, and they usually lead to serious uncertainty in hydrological and meteorological applications. In order to provide accurate rain area delineation for retrieving high-resolution precipitation datasets using satellite microwave observations, a probabilistic neural network (PNN-based rain area delineation method was developed with rain gauge observations over the Yangtze River Basin and three parameters, including polarization corrected temperature at 85 GHz, difference of brightness temperature at vertically polarized 37 and 19 GHz channels (termed as TB37V and TB19V, respectively and the sum of TB37V and TB19V derived from the observations of the Tropical Rainfall Measuring Mission (TRMM Microwave Imager (TMI. The PNN method was validated with independent samples, and the performance of this method was compared with dynamic cluster K-means method, TRMM Microwave Imager (TMI Level 2 Hydrometeor Profile Product and the threshold method used in the Scatter Index (SI, a widely used microwave-based precipitation retrieval algorithm. Independent validation indicated that the PNN method can provide more reasonable rain areas than the other three methods. Furthermore, the precipitation volumes estimated by the SI algorithm were significantly improved by substituting the PNN method for the threshold method in the traditional SI algorithm. This study suggests that PNN is a promising way to obtain reasonable rain areas with satellite observations, and the development of an accurate rain area delineation method deserves more attention for improving the accuracy of satellite precipitation datasets.

  11. Immunization alters body odor.

    Science.gov (United States)

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. Published by Elsevier Inc.

  12. Automated volume of interest delineation and rendering of cone beam CT images in interventional cardiology

    Science.gov (United States)

    Lorenz, Cristian; Schäfer, Dirk; Eshuis, Peter; Carroll, John; Grass, Michael

    2012-02-01

    Interventional C-arm systems allow the efficient acquisition of 3D cone beam CT images. They can be used for intervention planning, navigation, and outcome assessment. We present a fast and completely automated volume of interest (VOI) delineation for cardiac interventions, covering the whole visceral cavity including mediastinum and lungs but leaving out rib-cage and spine. The problem is addressed in a model based approach. The procedure has been evaluated on 22 patient cases and achieves an average surface error below 2mm. The method is able to cope with varying image intensities, varying truncations due to the limited reconstruction volume, and partially with heavy metal and motion artifacts.

  13. DELINEATION OF BOUNDARY CONTOURS OF MINERAL RAW MATERIALS WITHIN THE DEPOSIT SPACE CONSIDERING THE QUALITY

    Directory of Open Access Journals (Sweden)

    Ivan Tomašić

    1990-12-01

    Full Text Available On the basis of performed explorations, in the phase of deposit preparation and development for exploitation the obtained results regarding the raw material quality were transfered to the surface. The results served both for the development and planning of deposit excavation dynamics and for the delineation of boundary contours by mineral raw materials within the deposit space considering the quality, The case presented in the article refers to the marl and limestone open pit for the cement industry, the »Partizan« near Split (the paper is published in Croatian.

  14. Dosimetric Consequences of Interobserver Variability in Delineating the Organs at Risk in Gynecologic Interstitial Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Damato, Antonio L., E-mail: adamato@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Townamchai, Kanopkis [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Albert, Michele [Department of Radiation Oncology, Saint Anne' s Hospital Regional Cancer Center, Fall River, Massachusetts (United States); Bair, Ryan J. [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Cormack, Robert A. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Jang, Joanne [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Kovacs, Arpad [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lee, Larissa J. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Mak, Kimberley S.; Mirabeau-Beale, Kristina L.; Mouw, Kent W.; Phillips, John G.; Pretz, Jennifer L.; Russo, Andrea L. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Lewis, John H.; Viswanathan, Akila N. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2014-07-01

    Purpose: To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. Methods and Materials: The rectum, bladder, and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CI{sub gen}), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D{sub 0.1cc} and D{sub 2cc} was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SD{sup TOT}) was calculated. Results: The population mean ± 1 standard deviation of κ, CI{sub gen}, and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08, and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08, and 20% ± 5% for rectum; and 0.33 ± 0.20, 0.26 ± 0.17, and 82% ± 42% for sigmoid. Dosimetric variability was as follows: for bladder, CV = 31% ± 19% (SD{sup TOT} = 72 ± 64 Gy) for D{sub 0.1cc} and CV = 16% ± 10% (SD{sup TOT} = 9 ± 6 Gy) for D{sub 2cc}; for rectum, CV = 11% ± 5% (SD{sup TOT} = 16 ± 17 Gy) for D{sub 0.1cc} and CV = 7% ± 2% (SD{sup TOT} = 4 ± 3 Gy) for D{sub 2cc}; for sigmoid, CV = 39% ± 28% (SD{sup TOT} = 12 ± 18 Gy) for D{sub 0.1cc} and CV = 34% ± 19% (SD{sup TOT} = 4 ± 4 Gy) for D{sub 2cc.} Conclusions: Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D{sub 0.1cc.} Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with

  15. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients

    International Nuclear Information System (INIS)

    Dolz, J.; Kirişli, H. A.; Massoptier, L.; Fechter, T.; Karnitzki, S.; Oehlke, O.; Nestle, U.; Vermandel, M.

    2016-01-01

    Purpose: Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Methods: Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Results: Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. Conclusions: An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs

  16. Delineating fresh water and brackish water aquifers by GIS and groundwater quality data

    International Nuclear Information System (INIS)

    Yasin, M.; Latif, M.

    2007-01-01

    This study was conducted in the Mona project area, Bhalwal, district Sargodha to delineate fresh water and brackish water aquifers by GIS (Geographic Information System) and historic groundwater quality data of 138 deep tube wells installed in the study area. The groundwater quality zonations were made by overlapping maps of TDS (Total Dissolved Solids), SAR (Sodium Adsorption Ratio) and RSC (Residual Sodium Carbonate). Seven zones of groundwater quality consisting of good, marginal, hazardous and their combinations were identified. The results indicated redistribution of salts in the aquifer and rise in water table in some parts of the study area from 1965-1997. (author)

  17. Delineation of major geologic structures in Turkey using SIR-B data

    Science.gov (United States)

    Toksoz, M. N.; Pettengill, G. H.; Ford, P.; Gulen, L.

    1984-01-01

    Shuttle Imaging Radar-B (SIR-B) images of well mapped segments of major faults, such as the North Anatolian Fault (NAF) and East Anatolian Fault (EAF) will be studied to identify the prominent signatures that characterize the fault zones for those specific regions. The information will be used to delineate the unmapped fault zones in areas with similar geological and geomorphological properties. The data obtained from SIR-B images will be compared and correlated with the LANDSAT thematic mapper and seismicity alignments based on well constrained earthquake epicenters.

  18. Dosimetric Consequences of Interobserver Variability in Delineating the Organs at Risk in Gynecologic Interstitial Brachytherapy

    International Nuclear Information System (INIS)

    Damato, Antonio L.; Townamchai, Kanopkis; Albert, Michele; Bair, Ryan J.; Cormack, Robert A.; Jang, Joanne; Kovacs, Arpad; Lee, Larissa J.; Mak, Kimberley S.; Mirabeau-Beale, Kristina L.; Mouw, Kent W.; Phillips, John G.; Pretz, Jennifer L.; Russo, Andrea L.; Lewis, John H.; Viswanathan, Akila N.

    2014-01-01

    Purpose: To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. Methods and Materials: The rectum, bladder, and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CI gen ), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D 0.1cc and D 2cc was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SD TOT ) was calculated. Results: The population mean ± 1 standard deviation of κ, CI gen , and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08, and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08, and 20% ± 5% for rectum; and 0.33 ± 0.20, 0.26 ± 0.17, and 82% ± 42% for sigmoid. Dosimetric variability was as follows: for bladder, CV = 31% ± 19% (SD TOT = 72 ± 64 Gy) for D 0.1cc and CV = 16% ± 10% (SD TOT = 9 ± 6 Gy) for D 2cc ; for rectum, CV = 11% ± 5% (SD TOT = 16 ± 17 Gy) for D 0.1cc and CV = 7% ± 2% (SD TOT = 4 ± 3 Gy) for D 2cc ; for sigmoid, CV = 39% ± 28% (SD TOT = 12 ± 18 Gy) for D 0.1cc and CV = 34% ± 19% (SD TOT = 4 ± 4 Gy) for D 2cc. Conclusions: Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D 0.1cc. Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the

  19. A tri-modality image fusion method for target delineation of brain tumors in radiotherapy.

    Directory of Open Access Journals (Sweden)

    Lu Guo

    Full Text Available To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors.A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT and tri-modality (MRI/CT/PET image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV, the average distance between surface and centroid (ADSC, and the local standard deviation (SDlocal. Analysis of COV was also performed to evaluate intra-observer volume variation.The inter-observer variation analysis showed that, the mean COV was 0.14(± 0.09 and 0.07(± 0.01 for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05 with tri-modality; SDlocal averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm and patient 3 (from 0.42 cm to 0.36 cm with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00 with the tri-modality method as compared with using the dual-modality method.With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.

  20. Investigation into the value of the seismic methods in delineating structure in southwestern Ontario

    Energy Technology Data Exchange (ETDEWEB)

    Hodgson, J H

    1948-12-31

    This paper constitutes the final report on a project that investigated the possibilities of seismic methods to delineate Palaeozoic structures in areas of hydrocarbon exploration in south-western Ontario. It begins with an introduction on the theory and practice of seismic reflection prospecting and the general Palaeozoic geology of the study area. It then describes the equipment used, preliminary investigations (alignment of instruments, velocity determinations), and field tests conducted over various hydrocarbon prospects. Finally, the feasibility of using seismic methods in the area is discussed along with reasons for difficulties experienced in the investigation.

  1. Emotional matters. Delineating the industry professional's view on emotion in video games.

    OpenAIRE

    SAARINEN, TUULI

    2012-01-01

    For the past 10 years, lack of emotion in video games has been a staple topic of discussion among game developers, despite the fact that numerous studies have shown that video games are capable of awakening a vast array of emotions in their players. The purpose of this study is to see what exactly is discussed when the topic is brought up and to delineate how this discussion is connected to the potential of the video game medium. I will be using a method called affinity diagram to analyse...

  2. Interactive contour delineation of organs at risk in radiotherapy: Clinical evaluation on NSCLC patients

    Energy Technology Data Exchange (ETDEWEB)

    Dolz, J., E-mail: jose.dolz.upv@gmail.com [AQUILAB, Loos-les-Lille 59120, France and University Lille, Inserm, CHU Lille, U1189–ONCO-THAI–Image Assisted Laser Therapy for Oncology, Lille F-59000 (France); Kirişli, H. A.; Massoptier, L. [AQUILAB, Loos-les-Lille 59120 (France); Fechter, T.; Karnitzki, S.; Oehlke, O.; Nestle, U. [Department of Radiation Oncology, University Medical Center, Freiburg 79106 (Germany); Vermandel, M. [Inserm Onco Thai U1189, Université Lille 2, CHRU Lille, Lille 59037 (France)

    2016-05-15

    Purpose: Accurate delineation of organs at risk (OARs) on computed tomography (CT) image is required for radiation treatment planning (RTP). Manual delineation of OARs being time consuming and prone to high interobserver variability, many (semi-) automatic methods have been proposed. However, most of them are specific to a particular OAR. Here, an interactive computer-assisted system able to segment various OARs required for thoracic radiation therapy is introduced. Methods: Segmentation information (foreground and background seeds) is interactively added by the user in any of the three main orthogonal views of the CT volume and is subsequently propagated within the whole volume. The proposed method is based on the combination of watershed transformation and graph-cuts algorithm, which is used as a powerful optimization technique to minimize the energy function. The OARs considered for thoracic radiation therapy are the lungs, spinal cord, trachea, proximal bronchus tree, heart, and esophagus. The method was evaluated on multivendor CT datasets of 30 patients. Two radiation oncologists participated in the study and manual delineations from the original RTP were used as ground truth for evaluation. Results: Delineation of the OARs obtained with the minimally interactive approach was approved to be usable for RTP in nearly 90% of the cases, excluding the esophagus, which segmentation was mostly rejected, thus leading to a gain of time ranging from 50% to 80% in RTP. Considering exclusively accepted cases, overall OARs, a Dice similarity coefficient higher than 0.7 and a Hausdorff distance below 10 mm with respect to the ground truth were achieved. In addition, the interobserver analysis did not highlight any statistically significant difference, at the exception of the segmentation of the heart, in terms of Hausdorff distance and volume difference. Conclusions: An interactive, accurate, fast, and easy-to-use computer-assisted system able to segment various OARs

  3. The landscape of genomic alterations across childhood cancers

    DEFF Research Database (Denmark)

    Gröbner, Susanne N; Worst, Barbara C; Weischenfeldt, Joachim

    2018-01-01

    Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adoles...

  4. Genetic GIScience

    DEFF Research Database (Denmark)

    Jacquez, Geoffrey; Sabel, Clive E; Shi, Chen

    2015-01-01

    The exposome, defined as the totality of an individual's exposures over the life course, is a seminal concept in the environmental health sciences. Although inherently geographic, the exposome as yet is unfamiliar to many geographers. This article proposes a place-based synthesis, genetic...... geographic information science (genetic GIScience), that is founded on the exposome, genome+, and behavome. It provides an improved understanding of human health in relation to biology (the genome+), environmental exposures (the exposome), and their social, societal, and behavioral determinants (the behavome......). Genetic GIScience poses three key needs: first, a mathematical foundation for emergent theory; second, process-based models that bridge biological and geographic scales; third, biologically plausible estimates of space?time disease lags. Compartmental models are a possible solution; this article develops...

  5. Desktop Genetics.

    Science.gov (United States)

    Hough, Soren H; Ajetunmobi, Ayokunmi; Brody, Leigh; Humphryes-Kirilov, Neil; Perello, Edward

    2016-11-01

    Desktop Genetics is a bioinformatics company building a gene-editing platform for personalized medicine. The company works with scientists around the world to design and execute state-of-the-art clustered regularly interspaced short palindromic repeats (CRISPR) experiments. Desktop Genetics feeds the lessons learned about experimental intent, single-guide RNA design and data from international genomics projects into a novel CRISPR artificial intelligence system. We believe that machine learning techniques can transform this information into a cognitive therapeutic development tool that will revolutionize medicine.

  6. Prospective Randomized Double-Blind Pilot Study of Site-Specific Consensus Atlas Implementation for Rectal Cancer Target Volume Delineation in the Cooperative Group Setting

    International Nuclear Information System (INIS)

    Fuller, Clifton D.; Nijkamp, Jasper; Duppen, Joop C.; Rasch, Coen R.N.; Thomas, Charles R.; Wang, Samuel J.; Okunieff, Paul; Jones, William E.; Baseman, Daniel; Patel, Shilpen; Demandante, Carlo G.N.; Harris, Anna M.; Smith, Benjamin D.; Katz, Alan W.; McGann, Camille

    2011-01-01

    Purpose: Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes. Methods and Materials: A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement). Results: Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure. Conclusion: Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.

  7. Prospective randomized double-blind pilot study of site-specific consensus atlas implementation for rectal cancer target volume delineation in the cooperative group setting

    Science.gov (United States)

    Fuller, Clifton D.; Nijkamp, Jasper; Duppen, Joop; Rasch, Coen R.N.; Thomas, Charles R.; Wang, Samuel J.; Okunieff, Paul; Jones, William E.; Baseman, Daniel; Patel, Shilpen; Demandante, Carlo G. N.; Harris, Anna M.; Smith, Benjamin D.; Katz, Alan W.; McGann, Camille; Harper, Jennifer L.; Chang, Daniel T.; Smalley, Stephen; Marshall, David T.; Goodman, Karyn A.; Papanikolaou, Niko; Kachnic, Lisa A.

    2010-01-01

    Purpose Variation in target volume delineation represents a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the impact of a consensus guideline-based visual atlas on contouring of target volumes. Methods A representative case and target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy were contoured (Scan1) by 14 physician observers and a reference expert. Gross tumor volume (GTV), and 2 clinical target volumes (CTVA, comprising internal iliac, pre-sacral, and peri-rectal nodes, and CTVB, external iliac nodes) were contoured. Observers were randomly assigned to receipt (Group_A) /non-receipt (Group_B) of a consensus guideline and atlas for anorectal cancers, then instructed to re-contour the same case/images (Scan2). Observer variation was analyzed volumetrically using conformation number (CN, where CN=1 equals a total agreement). Results In 14 evaluable contour sets (1 expert, 7 Group_A, 6 Group_B), there was greater agreement for GTV (mean CN 0.75) than CTVs (mean CN 0.46–0.65). Atlas exposure for Group_A led to a significant increased inter-observer agreement for CTVA (mean initial CN 0.68, post-atlas 0.76; p=0.03), as well as increased agreement with the expert reference (initial mean CN 0.58, 0.69 post-atlas; p=0.02). For GTV and CTVB, neither inter-observer nor expert agreement was altered after atlas exposure. Conclusion Consensus guideline atlas implementation resulted in a detectable difference in inter-observer agreement and greater approximation of expert volumes for CTVA, but not GTV or CTVB, in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal radiotherapy. PMID:20400244

  8. Knee extension and flexion: MR delineation of normal and torn anterior cruciate ligaments

    Energy Technology Data Exchange (ETDEWEB)

    Niitsu, Mamoru; Ikeda, Kotaroh; Fukubayashi, Tohru; Anno, Izumi; Itai, Yuji [Univ. of Tsukuba, Ibaraki (Japan)

    1996-03-01

    Our goal was to assess the effect of joint position of semiflexed and extended knees in MR delineation of the anterior cruciate ligament (ACL). With a mobile knee brace and a flexible surface coil, the knee joint was either fully extended or bent to a semiflexed position (average 45{degrees} of flexion) within the magnet bore. Sets of oblique sagittal MR images were obtained for both extended and flexed knee positions. Thirty-two knees with intact ACLs and 43 knees with arthroscopically proven ACL tears were evaluated. Two observers compared paired MR images of both extended and flexed positions and rated them by a relative three point scale. Anatomic correlation in MR images was obtained by a cadaveric knee with incremental flexion. The MR images of flexed knees were more useful than of extended knees in 53% of the case reviews of femoral attachments and 36% of reviews of midportions of normal ACLs. Compared with knee extensions, the MR images for knee flexion provided better clarity in 48% of reviews of disrupted sites and 52% of residual bundles of torn ACLs. Normal ACL appeared taut in the knee extension and lax in semiflexion. Compared with MR images of knees in extension, MR images of knees in flexion more clearly delineate the femoral side of the ligament with wider space under the intercondylar roof and with decreased volume-averaging artifacts, providing superior visualization of normal and torn ACLs. 13 refs., 7 figs., 1 tab.

  9. An Intraoperative Visualization System Using Hyperspectral Imaging to Aid in Brain Tumor Delineation

    Directory of Open Access Journals (Sweden)

    Himar Fabelo

    2018-02-01

    Full Text Available Hyperspectral imaging (HSI allows for the acquisition of large numbers of spectral bands throughout the electromagnetic spectrum (within and beyond the visual range with respect to the surface of scenes captured by sensors. Using this information and a set of complex classification algorithms, it is possible to determine which material or substance is located in each pixel. The work presented in this paper aims to exploit the characteristics of HSI to develop a demonstrator capable of delineating tumor tissue from brain tissue during neurosurgical operations. Improved delineation of tumor boundaries is expected to improve the results of surgery. The developed demonstrator is composed of two hyperspectral cameras covering a spectral range of 400–1700 nm. Furthermore, a hardware accelerator connected to a control unit is used to speed up the hyperspectral brain cancer detection algorithm to achieve processing during the time of surgery. A labeled dataset comprised of more than 300,000 spectral signatures is used as the training dataset for the supervised stage of the classification algorithm. In this preliminary study, thematic maps obtained from a validation database of seven hyperspectral images of in vivo brain tissue captured and processed during neurosurgical operations demonstrate that the system is able to discriminate between normal and tumor tissue in the brain. The results can be provided during the surgical procedure (~1 min, making it a practical system for neurosurgeons to use in the near future to improve excision and potentially improve patient outcomes.

  10. Accuracy verification of PET-CT image fusion and its utilization in target delineation of radiotherapy

    International Nuclear Information System (INIS)

    Wang Xuetao; Yu Jinming; Yang Guoren; Gong Heyi

    2005-01-01

    Objective: Evaluate the accuracy of co-registration of PET and CT (PET-CT) images on line with phantom, and utilize it on patients to provide clinical evidence for target delineation in radiotherapy. Methods: A phantom with markers and different volume cylinders was infused with various concentrations of 18 FDG, and scanned at 4 mm by PET and CT respectively. After having been transmitted into GE eNTEGRA and treatment planning system (TPS) workstations, the images were fused and reconstructed. The distance between the markers and the errors were monitored in PET and CT images respectively. The volume of cylinder in PET and CT images were measured and compared by certain pixel value proportion deduction method. The same procedure was performed on the pulmonary tumor image in ten patients. Results: eNTEGRA and TPS workstations had a good length linearity, but the fusion error of the latter was markedly greater than the former. Tumors in different volume filled by varying concentrations of 18 FDG required different pixel deduction proportion. The cylinder volume of PET and CT images were almost the same, so were the images of pulmonary tumor of ten patients. Conclusions: The accuracy of image co-registration of PET-CT on line may fulfill the clinical demand. Pixel value proportion deduction method can be used for target delineation on PET image. (authors)

  11. What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

    International Nuclear Information System (INIS)

    Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A.; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

    2005-01-01

    Purpose: To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. Methods and Materials: A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. Results: A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. Conclusions: The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy

  12. What is the microscopic tumor extent beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers?

    Science.gov (United States)

    Choo, Richard; Woo, Tony; Assaad, Dalal; Antonyshyn, Oleh; Barnes, Elizabeth A; McKenzie, David; Fialkov, Jeffrey; Breen, Dale; Mamedov, Alexander

    2005-07-15

    To quantify the microscopic tumor extension beyond clinically delineated gross tumor boundary in nonmelanoma skin cancers. A prospective, single arm, study. Preoperatively, a radiation oncologist outlined the boundary of a gross lesion, and drew 5-mm incremental marks in four directions from the delineated border. Under local anesthesia, the lesion was excised, and resection margins were assessed microscopically by frozen section. Once resection margins were clear, the microscopic tumor extent was calculated using the presurgical incremental markings as references. A potential relationship between the distance of microscopic tumor extension and other variables was analyzed. A total of 71 lesions in 64 consecutive patients, selected for surgical excision with frozen-section-assisted assessment of resection margins, were accrued. The distance of microscopic tumor extension beyond a gross lesion varied from 1 mm to 15 mm, with a mean of 5.2 mm. A margin of 10 mm was required to provide a 95% chance of obtaining clear resection margins. The microscopic tumor extent was positively correlated with the size of gross lesion, but not with other variables. The distance of microscopic tumor extension beyond a gross nonmelanoma skin cancer was variable, with a mean of 5.2 mm. Such information is critical for the proper radiation planning of skin cancer therapy.

  13. Delineating gas bearing reservoir by using spectral decomposition attribute: Case study of Steenkool formation, Bintuni Basin

    Science.gov (United States)

    Haris, A.; Pradana, G. S.; Riyanto, A.

    2017-07-01

    Tectonic setting of the Bird Head Papua Island becomes an important model for petroleum system in Eastern part of Indonesia. The current exploration has been started since the oil seepage finding in Bintuni and Salawati Basin. The biogenic gas in shallow layer turns out to become an interesting issue in the hydrocarbon exploration. The hydrocarbon accumulation appearance in a shallow layer with dry gas type, appeal biogenic gas for further research. This paper aims at delineating the sweet spot hydrocarbon potential in shallow layer by applying the spectral decomposition technique. The spectral decomposition is decomposing the seismic signal into an individual frequency, which has significant geological meaning. One of spectral decomposition methods is Continuous Wavelet Transform (CWT), which transforms the seismic signal into individual time and frequency simultaneously. This method is able to make easier time-frequency map analysis. When time resolution increases, the frequency resolution will be decreased, and vice versa. In this study, we perform low-frequency shadow zone analysis in which the amplitude anomaly at a low frequency of 15 Hz was observed and we then compare it to the amplitude at the mid (20 Hz) and the high-frequency (30 Hz). The appearance of the amplitude anomaly at a low frequency was disappeared at high frequency, this anomaly disappears. The spectral decomposition by using CWT algorithm has been successfully applied to delineate the sweet spot zone.

  14. Improving superficial target delineation in radiation therapy with endoscopic tracking and registration

    Energy Technology Data Exchange (ETDEWEB)

    Weersink, R. A.; Qiu, J.; Hope, A. J.; Daly, M. J.; Cho, B. C. J.; DaCosta, R. S.; Sharpe, M. B.; Breen, S. L.; Chan, H.; Jaffray, D. A. [Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 2M9 (Canada) and Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2M9 (Canada)

    2011-12-15

    Purpose: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging. Methods: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration. Results: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0

  15. New Genetics

    Science.gov (United States)

    ... of the booklet. » more Chapter 1: How Genes Work Covers DNA, RNA, transcription, RNA splicing, translation, ribosomes, antibiotics, genetic diseases, gene chips. » more Chapter 2: RNA and DNA Revealed: New Roles, New Rules Covers microRNAs, RNAi, epigenetics, telomeres, mtDNA, recombinant DNA. » ...

  16. Genetic effects

    International Nuclear Information System (INIS)

    Kato, Hiroo

    1975-01-01

    In 1948-1953 a large scale field survey was conducted to investigate the possible genetic effects of A-bomb radiation on over 70,000 pregnancy terminations in the cities of Hiroshima and Nagasaki. The indices of possible genetic effect including sex ratio, birth weight, frequency of malformation, stillbirth, neonatal death, deaths within 9 months and anthropometric measurements at 9 months of age for these children were investigated in relation to their parent's exposure status to the A-bomb. There were no detectable genetic effects in this sample, except for a slight change in sex ratio which was in the direction to be expected if exposure had induced sex-linked lethal mutations. However, continued study of the sex ratio, based upon birth certificates in Hiroshima and Nagasaki for 1954-1962, did not confirm the earlier trend. Mortality in these children of A-bomb survivors is being followed using a cohort of 54,000 subjects. No clearly significant effect of parental exposure on survival of the children has been demonstrated up to 1972 (age 17 on the average). On the basis of the regression data, the minimal genetic doubling dose of this type of radiation for mutations resulting in death is estimated at 46 rem for the father and 125 rem for the mother. (auth.)

  17. Genetic Recombination

    Science.gov (United States)

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  18. Genetic analysis

    NARCIS (Netherlands)

    Koornneef, M.; Alonso-Blanco, C.; Stam, P.

    2006-01-01

    The Mendelian analysis of genetic variation, available as induced mutants or as natural variation, requires a number of steps that are described in this chapter. These include the determination of the number of genes involved in the observed trait's variation, the determination of dominance

  19. Molecular genetics

    International Nuclear Information System (INIS)

    Parkinson, D.R.; Krontiris, T.G.

    1986-01-01

    In this chapter the authors review new findings concerning the molecular genetics of malignant melanoma in the context of other information obtained from clinical, epidemiologic, and cytogenetic studies in this malignancy. These new molecular approaches promise to provide a more complete understanding of the mechanisms involved in the development of melanoma, thereby suggesting new methods for its treatment and prevention

  20. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  1. J. Genet. classic 235

    Indian Academy of Sciences (India)

    Unknown

    Journal of Genetics, Vol. 83, No. 3, December 2004. 235. Page 2. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 236. Page 3. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 237. Page 4. J. Genet. classic. Journal of Genetics, Vol. 83, No. 3, December 2004. 238. Page 5 ...

  2. [Genetics of congenital heart diseases].

    Science.gov (United States)

    Bonnet, Damien

    2017-06-01

    Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Genetic effects

    International Nuclear Information System (INIS)

    Bender, M.A.; Abrahamson, S.; Denniston, C.; Schull, W.J.

    1989-01-01

    In this chapter, we present a comprehensive analysis of the major classes of genetic diseases that would be increased as a result of an increased gonadal radiation exposure to a human population. The risk analysis takes on two major forms: the increase in genetic disease that would be observed in the immediate offspring of the exposed population, and the subsequent transmission of the newly induced mutations through future generations. The major classes of genetic disease will be induced at different frequencies, and will also impact differentially in terms of survivability and fertility on the affected individuals and their descendants. Some classes of disease will be expected to persist for only a few generations at most. Other types of genetic disease will persist through a longer period. The classes of genetic diseases studied are: dominant gene mutation, X-linked gene mutation, chromosome disorders and multifactorial disorders which involve the interaction of many mutant genes and environmental factors. For each of these classes we have derived the general equations of mutation induction for the male and female germ cells of critical importance in the mutation process. The frequency of induced mutations will be determined initially by the dose received, the type of radiation and, to some extent at high dose, by the manner in which the dose is received. We have used the modeling analyses to predict the outcomes for two nuclear power plant accident scenarios, the first in which the population receives a chronic dose of 0.1 Gy (10 rad) over a 50-year period, the second in which an equivalent population receives an acute dose of 2 Gy. In both cases the analyses are projected over a period of five generations

  4. Monitoring adaptive genetic responses to environmental change

    DEFF Research Database (Denmark)

    Hansen, M.M.; Olivieri, I.; Waller, D.M.

    2012-01-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

  5. Phantom study on three-dimensional target volume delineation by PET/CT-based auto-contouring

    International Nuclear Information System (INIS)

    Zhang, Tiejiao; Sakaguchi, Yuichi; Mitsumoto, Katsuhiko; Mitsumoto, Tatsuya; Sasaki, Masayuki; Tachiya, Yosuke; Ohya, Nobuyoshi

    2010-01-01

    The aim of this study was to determine an appropriate threshold value for delineation of the target volume in positron emission tomography (PET)/CT and to investigate whether we could delineate a target volume by phantom studies. A phantom consisted of six spheres (φ10-37 mm) filled with 18 F solution. Data acquisition was performed PET/CT in non-motion and motion status with high 18 F solution and in non-motion status with low 18 F solution. In non-motion phantom experiments, we determined two types of threshold value, an absolute SUV (T SUV ) and a percentage of the maximum SUV (T % ). Delineation using threshold values was applied for all spheres and for selected large spheres (a diameter of 22 mm or larger). In motion phantom experiments, data acquisition was performed in a static mode (sPET) and a gated mode (gPET). CT scanning was performed with helical CT (HCT) and 4-dimentional CT (4DCT). The appropriate threshold values were aT % =27% and aT SUV =2.4 for all spheres, and sT % =30% and sT SUV =4.3 for selected spheres. For all spheres in sPET/HCT in motion, the delineated volumes were 84%-129% by the aT % and 34%-127% by the aT SUV . In gPET/4DCT in motion, the delineated volumes were 94-103% by the aT % and 51-131% by the aT SUV . For low radioactivity spheres, the delineated volumes were all underestimated. A threshold value of T % =27% was proposed for auto-contouring of lung tumors. Our results also suggested that the respiratory gated data acquisition should be performed in both PET and CT for target volume delineation. (author)

  6. [Genetic diagnostics of cancer diseases].

    Science.gov (United States)

    Cobilanschi, Joana

    2013-11-27

    Cancer is caused by genetic alterations, but only 10% of the cancer diseases are inherited. The probability for an individual or a family of having inherited cancer, individual consequences of the respective results of genetic testing, as well as its costs and reimbursement by the health insurance must be addressed by expert genetic counseling which at-risk requires special expertise. Identification of a germline mutation which may predispose to a variety of different cancer types allows determination of an individual's specific life time risk in symptomatic as well as in a-symptomatic family members. Identification of the underlying defective gene in heritable cancer disorders also enables optimized preventive and novel therapeutic approaches specifically targeting the underlying molecular pathomechanisms.

  7. GENETICS ASPECTS OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Oana-Elena Sauca

    2010-09-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alteration, and various growth and genetic factors. The identification of the main genes would allow the detection of those individuals at high risk for diabetic nephropathy and better understanding of its pathophysiologyas well.The present review discusses the main information available in literature regarding some genetic variants (involved in the renin-angiotensin system, glucose and lipid metabolism and some cytoskeleton proteins that reaffirms the importance of genetic factors in diabetic nephropathy.

  8. Molecular-genetic analysis of two cases with retinoblastoma ...

    Indian Academy of Sciences (India)

    Unknown

    Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of ... to chromosomal deletion, single-nucleotide alteration, microdeletion, loss ... informed consent of the parent.

  9. Progress in cancer genetics: lessons from pancreatic cancer

    NARCIS (Netherlands)

    Goggins, M.; Kern, S. E.; Offerhaus, J. A.; Hruban, R. H.

    1999-01-01

    In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. The literature was reviewed concerning the genetic alterations that

  10. A multimodality segmentation framework for automatic target delineation in head and neck radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jinzhong; Aristophanous, Michalis, E-mail: MAristophanous@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Beadle, Beth M.; Garden, Adam S. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Schwartz, David L. [Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 (United States)

    2015-09-15

    Purpose: To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to delineate target volume in head and neck cancer radiotherapy. Methods: Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1-weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation–maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician-defined gross tumor volume (GTV) was used as the “ground truth” for quantitative evaluation. Results: The median multichannel segmented GTV of the primary tumor was 15.7 cm{sup 3} (range, 6.6–44.3 cm{sup 3}), while the PET segmented GTV was 10.2 cm{sup 3} (range, 2.8–45.1 cm{sup 3}). The median physician-defined GTV was 22.1 cm{sup 3} (range, 4.2–38.4 cm{sup 3}). The median difference between the multichannel segmented and physician-defined GTVs was −10.7%, not showing a statistically significant difference (p-value = 0.43). However, the median difference between the PET segmented and physician-defined GTVs was −19.2%, showing a statistically significant difference (p-value =0.0037). The median Dice similarity coefficient between the multichannel segmented

  11. A multimodality segmentation framework for automatic target delineation in head and neck radiotherapy.

    Science.gov (United States)

    Yang, Jinzhong; Beadle, Beth M; Garden, Adam S; Schwartz, David L; Aristophanous, Michalis

    2015-09-01

    To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to delineate target volume in head and neck cancer radiotherapy. Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1-weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation-maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician-defined gross tumor volume (GTV) was used as the "ground truth" for quantitative evaluation. The median multichannel segmented GTV of the primary tumor was 15.7 cm(3) (range, 6.6-44.3 cm(3)), while the PET segmented GTV was 10.2 cm(3) (range, 2.8-45.1 cm(3)). The median physician-defined GTV was 22.1 cm(3) (range, 4.2-38.4 cm(3)). The median difference between the multichannel segmented and physician-defined GTVs was -10.7%, not showing a statistically significant difference (p-value = 0.43). However, the median difference between the PET segmented and physician-defined GTVs was -19.2%, showing a statistically significant difference (p-value =0.0037). The median Dice similarity coefficient between the multichannel segmented and physician-defined GTVs was 0.75 (range, 0.55-0.84), and the

  12. Postoperative radiation in esophageal squamous cell carcinoma and target volume delineation

    Directory of Open Access Journals (Sweden)

    Zhu Y

    2016-07-01

    Full Text Available Yingming Zhu,* Minghuan Li,* Li Kong, Jinming Yu Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Esophageal cancer is the sixth leading cause of cancer death worldwide, and patients who are treated with surgery alone, without neoadjuvant therapies, experience frequent relapses. Whether postoperative therapies could reduce the recurrence or improve overall survival is still controversial for these patients. The purpose of our review is to figure out the value of postoperative adjuvant therapy and address the disputes about target volume delineation according to published data. Based on the evidence of increased morbidity and disadvantages on patient survival caused by postoperative chemotherapy or radiotherapy (RT alone provided by studies in the early 1990s, the use of postoperative adjuvant therapies in cases of esophageal squamous cell carcinoma has diminished substantially and has been replaced gradually by neoadjuvant chemoradiation. With advances in surgery and RT, accumulating evidence has recently rekindled interest in the delivery of postoperative RT or chemoradiotherapy in patients with stage T3/T4 or N1 (lymph node positive carcinomas after radical surgery. However, due to complications with the standard radiation field, a nonconforming modified field has been adopted in most studies. Therefore, we analyze different field applications and provide suggestions on the optimization of the radiation field based on the major sites of relapse and the surgical non-clearance area. For upper and middle thoracic esophageal carcinomas, the bilateral supraclavicular and superior mediastinal areas remain common sites of recurrence and should be encompassed within the clinical target volume. In contrast, a consensus has yet to be reached regarding lower thoracic esophageal carcinomas; the

  13. Delineating demographic units of woodland caribou (Rangifer tarandus caribou in Ontario: cautions and insights

    Directory of Open Access Journals (Sweden)

    Jennifer L. Shuter

    2012-03-01

    Full Text Available Delineating demographic structure across an organism’s range can reveal the extent to which population dynamics in different geographic areas are driven by local or external factors and can be crucial for effective conservation and management. Obtaining optimal data for such analyses can be time and resource-intensive and impending development and resource extraction pressures may necessitate the examination of existing data, even when they are less than ideal. We analyzed a historic telemetry dataset containing satellite radio-collar locations of 73 forest-dwelling woodland caribou in northern Ontario to determine demographic structure. We applied several clustering methods (i.e., agglomerative, divisive and fuzzy k-means to median seasonal locations. Results were used to distinguish demographic units and minimum convex polygons and fixed-kernel density estimates were used to delineate unit boundaries and core areas. For areas where sampling was considered representative of the distribution of caribou on the landscape, we assessed demographic distinctness by evaluating intra-individual variation in cluster membership, membership strength and distance between boundaries and core areas of adjacent units. The number and composition of clusters identified was similar among methods and caribou were grouped into 6 general clusters. The distinctions between the three clusters identified in the central portion of the province (i.e., Lac Seul, Wabakimi, Geraldton and the two clusters identified in the eastern portion of the province (i.e., Cochrane and Cochrane-Quebec were determined to represent demographic structuring. Additional distinctions in other areas (i.e., between The Red Lake and Lac Seul clusters in the west and between the central and eastern clusters may just be artifacts of the original sampling effort. Amongst demographic units, there was no evidence of individual flexibility in cluster membership and average membership strength was

  14. A multimodality segmentation framework for automatic target delineation in head and neck radiotherapy

    International Nuclear Information System (INIS)

    Yang, Jinzhong; Aristophanous, Michalis; Beadle, Beth M.; Garden, Adam S.; Schwartz, David L.

    2015-01-01

    Purpose: To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to delineate target volume in head and neck cancer radiotherapy. Methods: Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1-weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation–maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician-defined gross tumor volume (GTV) was used as the “ground truth” for quantitative evaluation. Results: The median multichannel segmented GTV of the primary tumor was 15.7 cm"3 (range, 6.6–44.3 cm"3), while the PET segmented GTV was 10.2 cm"3 (range, 2.8–45.1 cm"3). The median physician-defined GTV was 22.1 cm"3 (range, 4.2–38.4 cm"3). The median difference between the multichannel segmented and physician-defined GTVs was −10.7%, not showing a statistically significant difference (p-value = 0.43). However, the median difference between the PET segmented and physician-defined GTVs was −19.2%, showing a statistically significant difference (p-value =0.0037). The median Dice similarity coefficient between the multichannel segmented and physician-defined GTVs was

  15. Delineation of wetland areas from high resolution WorldView-2 data by object-based method

    International Nuclear Information System (INIS)

    Hassan, N; Hamid, J R A; Adnan, N A; Jaafar, M

    2014-01-01

    Various classification methods are available that can be used to delineate land cover types. Object-based is one of such methods for delineating the land cover from satellite imageries. This paper focuses on the digital image processing aspects of discriminating wetland areas via object-based method using high resolution satellite multispectral WorldView-2 image data taken over part of Penang Island region. This research is an attempt to improve the wetland area delineation in conjunction with a range of classification techniques which can be applied to satellite data with high spatial and spectral resolution such as World View 2. The intent is to determine a suitable approach to delineate and map these wetland areas more appropriately. There are common parameters to take into account that are pivotal in object-based method which are the spatial resolution and the range of spectral channels of the imaging sensor system. The preliminary results of the study showed object-based analysis is capable of delineating wetland region of interest with an accuracy that is acceptable to the required tolerance for land cover classification

  16. Market delineation and system competition. The 'Bedarfsmarktkonzept' on trial; Marktabgrenzung und Systemwettbewerb. Das Bedarfsmarktkonzept auf dem Pruefstand

    Energy Technology Data Exchange (ETDEWEB)

    Vahrenholt, Oliver

    2011-07-01

    The fundamental research question of this thesis is whether, and under conditions, competitive constraints arising out of competition between systems should be reflected in antitrust market delineation. In order to answer this question, it is necessary to understand the function of market delineation in antitrust law. This is the first research question the thesis addresses. The function of market delineation is intrinsically tied to the concept of market power. Market power and its possible negative effects on total welfare and especially on consumer welfare serve as the central legitimation for governmental intervention into the free play of market forces. In order to see how system competition fits into this free play of market forces and how market power can be established in light of these constraining forces, the central economic mechanism of system competition have to be understood. This leads to the second research question to be answered by this dissertation. The final, central question raised and answered in this thesis is how can market delineation perform its task in the presence of system competition forces, and which concepts are most suitable for accomplishing this end. A concrete concept - devised for the needs o