Science.gov

Sample records for 2q b2y 2q

  1. Deletion (2)(q37)

    SciTech Connect

    Stratton, R.F.; Tolworthy, J.A.; Young, R.S.

    1994-06-01

    We report on a 5-month-old girl with widely spaced nipples, redundant nuchal skin, coarctation of the aorta, anal atresia with distal fistula, postnatal growth retardation, hypotonia, and sparse scalp hair. Initial clinical assessment suggested the diagnosis of Ullrich-Turner syndrome. Chromosome analysis showed a 46,XX,del(2)(q37) karyotype in peripheral lymphocytes. We compare her findings to those of other reported patients with terminal deletions of 2q. 8 refs., 2 figs., 1 tab.

  2. Regional mapping of loci from human chromosome 2q to sheep chromosome 2q

    SciTech Connect

    Ansari, H.A.; Pearce, P.D.; Maher, D.W.; Malcolm, A.A.; Wood, N.J.; Phua, S.H.; Broad, T.E. )

    1994-03-01

    The human chromosome 2q loci, fibronectin 1 (FN1), the [alpha]1 chain of type III collagen (COL3A1), and the [delta] subunit of the muscle acetylcholine receptor (CHRND) have been regionally assigned to sheep chromosome 2q by in situ hybridization. COL3A1 is pericentromeric (2q12-q21), while FN1 and CHRND are in the subterminal region at 2q41-q44 and 2q42-qter, respectively. The mapping of FN1 assigns the sheep synthenic group U11, which contains FN1, villin 1 (VIL1), isocitrate dehydrogenase 1 (IDH1), and [gamma] subunit of the muscle acetylcholine receptor (CHRNG), to sheep chromosome 2q. Inhibin-[alpha] (INHA) is also assigned to sheep chromosome 2q as FN1 and INHA compose sheep linkage group 3. These seven loci are members of a conserved chromosomal segment in human, mouse, and sheep. 23 refs., 2 figs., 1 tab.

  3. Trisomy 2q11.2-->q21.1 resulting from an unbalanced insertion in two generations.

    PubMed Central

    Glass, I A; Stormer, P; Oei, P T; Hacking, E; Cotter, P D

    1998-01-01

    In this communication, we describe two cases of proximal 2q trisomy (2q11.2--> q21.1) resulting from an interchromosomal insertion. The chromosomal origin of the insertion was confirmed by fluorescence in situ hybridisation. An unbalanced karyotype, 46,XX,der(8) ,ins(8;2) (p21.3; q21.1q11.2), was found in the proband and her mother, who both have mild mental retardation, short stature, dysmorphic features, insulin dependent diabetes mellitus, and a psychotic illness. This family is a rare example of direct transmission of a partial autosomal trisomy. Images PMID:9598728

  4. Paroxysmal dystonic choreoathetosis: tight linkage to chromosome 2q.

    PubMed Central

    Fink, J. K.; Rainer, S.; Wilkowski, J.; Jones, S. M.; Kume, A.; Hedera, P.; Albin, R.; Mathay, J.; Girbach, L.; Varvil, T.; Otterud, B.; Leppert, M.

    1996-01-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery of the PDC gene and enable investigators to determine whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. PMID:8659518

  5. Paroxysmal dystonic choreoathetosis: Tight linkage to chromosome 2q

    SciTech Connect

    Fink, J.K.; Rainier, S.; Wilkowski, J.; Jones, S.M.

    1996-07-01

    Paroxysmal dystonic choreoathetosis (PDC) is characterized by attacks of involuntary movements that last up to several hours and occur at rest both spontaneously and following caffeine or alcohol consumption. We analyzed a Polish-American kindred with autosomal dominant PDC and identified tight linkage between the disorder and microsatellite markers on chromosome 2q (maximum two-point LOD score 4.77; recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant PDC on distal chromosome 2q. The fact that three other paroxysmal neurological disorders (periodic ataxia with myokymia and hypo- and hyperkalemic periodic paralysis) are due to mutation in ion-channel genes raises the possibility that PDC is also due to an ion-channel gene mutation. It is noteworthy that a cluster of sodium-channel genes is located on distal chromosome 2q, near the PDC locus. Identifying the PDC locus on chromosome 2q will facilitate discovery whether PDC is genetically homogeneous and whether other paroxysmal movement disorders are also genetically linked to the PDC locus. 28 refs., 2 figs., 1 tab.

  6. 2Q-LEBT Prototype for the RIA Facility

    SciTech Connect

    Vinogradov, N.E.; Aseev, V.N.; Kern, M.R.L.; Ostroumov, P.N.; Pardo, R.C.; Scott, R.; Vondrasek, R.C.

    2005-03-15

    The Rare Isotope Accelerator (RIA) facility utilizes the concept of simultaneous acceleration of two charge states from the ion source. We are building a prototype two charge-state (2Q) injector of the RIA Driver Linac, which includes an ECR ion source, a LEBT and one-segment of the prototype RFQ. Currently, the 2Q-LEBT Facility consists of Berkeley Ion Equipment Corporation BIE-100 ECR ion source. The rf transmitters, high voltage power supplies, turbo pumps and other related equipment were received with the source. BIE-100 is an all-permanent-magnet source and has the highest magnetic field strengths for an ECR ion source of this type ever built. The magnetic field achieves a maximum strength of 11 kG at the plasma chamber surface and 13 kG on the axis. The source can operate with two-frequency plasma heating of 12.75 and 14.5 GHz. The reassembly of the source has been completed and beam production was achieved in the June 2004. This report includes measured beam current and emittance for 16O from the source along with the beam dynamics simulations. Detailed design of the 2Q-LEBT and the current project status are also presented.

  7. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome).

    PubMed

    Roberts, Aedan; Nancarrow, Derek; Clendenning, Mark; Buchanan, Daniel D; Jenkins, Mark A; Duggan, David; Taverna, Darin; McKeone, Diane; Walters, Rhiannon; Walsh, Michael D; Young, Bruce W; Jass, Jeremy R; Rosty, Christophe; Gattas, Michael; Pelzer, Elise; Hopper, John L; Goldblatt, Jack; George, Jill; Suthers, Graeme K; Phillips, Kerry; Parry, Susan; Woodall, Sonja; Arnold, Julie; Tucker, Kathy; Muir, Amanda; Drini, Musa; Macrae, Finlay; Newcomb, Polly; Potter, John D; Pavluk, Erika; Lindblom, Annika; Young, Joanne P

    2011-06-01

    Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

  8. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

    PubMed

    Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

    2010-09-01

    We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

  9. Status of the 2Q-LEBT facility at ANL.

    SciTech Connect

    Scott, R. H.; Asseev, V. N.; Kulevoy, T. V.; Ostroumov, P. N.; Poklonskaya, E. A.; Sengupta, M.; Vinogradov, N. E.; Physics; ITEP; St. Petersburg Electrochemical Univ.; Northern Illinois Univ.

    2007-07-01

    The concept for a 2 charge state injector for a 'RIA type' accelerator has been presented. Progress toward an operational prototype 2Q-LEBT system at Argonne National Laboratory (ANL) is under way. The existing BIE 100 all permanent magnet ECR has been placed on a high voltage platform capable of a combined >100kV with q/m separation at ground level. Remote control of the devices on the platform has been implemented. Other components of the facility are currently being tested. The components of an achromatic bending system are currently being procured. This paper will present recent work at the facility as well as preliminary development of solid materials using the BIE 100.

  10. 2Q NMR of 2H2O ordering at solid interfaces

    NASA Astrophysics Data System (ADS)

    Krivokhizhina, Tatiana V.; Wittebort, R. J.

    2014-06-01

    Solvent ordering at an interface can be studied by multiple-quantum NMR. Quantitative studies of 2H2O ordering require clean double-quantum (2Q) filtration and an analysis of 2Q buildup curves that accounts for relaxation and, if randomly oriented samples are used, the distribution of residual couplings. A pulse sequence with absorption mode detection is extended for separating coherences by order and measuring relaxation times such as the 2Q filtered T2. Coherence separation is used to verify 2Q filtration and the 2Q filtered T2 is required to extract the coupling from the 2Q buildup curve when it is unresolved. With our analysis, the coupling extracted from the buildup curve in 2H2O hydrated collagen was equivalent to the resolved coupling measured in the usual 1D experiment and the 2Q to 1Q signal ratio was in accord with theory. Application to buildup curves from 2H2O hydrated elastin, which has an unresolved coupling, revealed a large increase in the 2Q signal upon mechanical stretch that is due to an increase in the ordered water fraction while changes in the residual coupling and T2 are small.

  11. Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication.

    PubMed

    Kishimoto, Keiko; Nomura, Jun; Ellegood, Jacob; Fukumoto, Keita; Lerch, Jason P; Moreno-De-Luca, Daniel; Bourgeron, Thomas; Tamada, Kota; Takumi, Toru

    2017-03-29

    Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis-1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin-1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome-based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication.

  12. Expression Status of UBE2Q2 in Colorectal Primary Tumors and Cell Lines

    PubMed Central

    Shafiee, Sayed Mohammad; Seghatoleslam, Atefeh; Nikseresht, Mohsen; Hosseini, Seyed Vahid; Alizadeh-Naeeni, Mahvash; Safaei, Akbar; Owji, Ali Akbar

    2014-01-01

    Background: Activation of the ubiquitin-proteasome pathway in various malignancies, including colorectal cancer, is established. This pathway mediates the degradation of damaged proteins and regulates growth and stress response. The novel human gene, UBE2Q2, with a putative ubiquitin-conjugating enzyme activity, is reported to be overexpressed in some malignancies. We sought to investigate the expression levels of the UBE2Q2 gene in colorectal cell lines as well as in cancerous and normal tissues from patients with colorectal cancer. Methods: Levels of UBE2Q2 mRNA in cell lines were assessed by Real-Time PCR. Western blotting was employed to investigate the levels of the UBE2Q2 protein in 8 colorectal cell lines and 43 colorectal tumor samples. Results: Expression of UBE2Q2 was observed at the level of both mRNA and protein in colorectal cell lines, HT29/219, LS180, SW742, Caco2, HTC116, SW48, SW480, and SW1116. Increased levels of UBE2Q2 immunoreactivity was observed in the 65.11% (28 out of 43) of the colorectal carcinoma tissues when compared with their corresponding normal tissues. Difference between the mean intensities of UBE2Q2 bands from cancerous and normal tissues was statistically significant at P<0.001 (paired t test). Conclusion: We showed the expression pattern of the novel human gene, UBE2Q2, in 8 colorectal cell lines. Overexpression of UBE2Q2 in the majority of the colorectal carcinoma samples denotes that it may have implications for the pathogenesis of colorectal cancer. PMID:24753643

  13. 49 CFR 178.33a - Specification 2Q; inner nonrefillable metal receptacles.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 2Q; inner nonrefillable metal receptacles. 178.33a Section 178.33a Transportation Other Regulations Relating to Transportation (Continued... nonrefillable metal receptacles....

  14. 49 CFR 178.33a - Specification 2Q; inner nonrefillable metal receptacles.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Specification 2Q; inner nonrefillable metal receptacles. 178.33a Section 178.33a Transportation Other Regulations Relating to Transportation PIPELINE AND... nonrefillable metal receptacles....

  15. 49 CFR 178.33a - Specification 2Q; inner nonrefillable metal receptacles.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 2Q; inner nonrefillable metal receptacles. 178.33a Section 178.33a Transportation Other Regulations Relating to Transportation (Continued... nonrefillable metal receptacles....

  16. 49 CFR 178.33a - Specification 2Q; inner nonrefillable metal receptacles.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Specification 2Q; inner nonrefillable metal receptacles. 178.33a Section 178.33a Transportation Other Regulations Relating to Transportation (Continued... nonrefillable metal receptacles....

  17. Progress with the 2Q-LEBT facility for the RIA project.

    SciTech Connect

    Vinogradov, N.; Aseev, V. N.; Kern, M. R. L.; Ostroumov, P. N.; Pardo, R. C.; Scott, R.; Physics

    2005-01-01

    The design goal of 400 kW uranium beam in the Rare Isotope Accelerator (RIA) Driver Linac can be achieved employing a concept of simultaneous acceleration of two charge states. It has been undertaken to build a prototype 2Q-injector of the RIA Driver Linac which includes an ECR ion source, a LEBT and one-segment of the prototype RFQ. The project called the 2Q-LEBT Facility is being developed in the Physics Division of ANL. Currently, the 2Q-LEBT Facility consists of BIE-100 ECR ion source. The reassembly and commissioning of the source has been completed. During the commissioning process we redesigned and manufactured a few components of the source to increase the beam production performance. A new diagnostic station has been designed and built for accurate measurements of the output beam emittance. The further development of the 2Q-LEBT Facility comprises installation of the source on 100 kV high-voltage platform, building an achromatic bending and transport system including the multi-harmonic buncher, and a full power 57.5 MHz RFQ segment. This report includes a detailed description of the 2Q-LEBT design and beam dynamics simulations along with emittance measurements for various beams.

  18. Significant Linkage of Parkinson Disease to Chromosome 2q36-37

    PubMed Central

    Pankratz, Nathan; Nichols, William C.; Uniacke, Sean K.; Halter, Cheryl; Rudolph, Alice; Shults, Cliff; Conneally, P. Michael; Foroud, Tatiana

    2003-01-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder, surpassed in frequency only by Alzheimer disease. Elsewhere we have reported linkage to chromosome 2q in a sample of sibling pairs with PD. We have now expanded our sample to include 150 families meeting our strictest diagnostic definition of verified PD. To further delineate the chromosome 2q linkage, we have performed analyses using only those pedigrees with the strongest family history of PD. Linkage analyses in this subset of 65 pedigrees generated a LOD score of 5.1, which was obtained using an autosomal dominant model of disease transmission. This result strongly suggests that variation in a gene on chromosome 2q36-37 contributes to PD susceptibility. PMID:12638082

  19. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    PubMed

    van Bon, Bregje W M; Koolen, David A; Brueton, Louise; McMullan, Dominic; Lichtenbelt, Klaske D; Adès, Lesley C; Peters, Gregory; Gibson, Kate; Moloney, Susan; Novara, Francesca; Pramparo, Tiziano; Dalla Bernardina, Bernardo; Zoccante, Leonardo; Balottin, Umberto; Piazza, Fausta; Pecile, Vanna; Gasparini, Paolo; Guerci, Veronica; Kets, Marleen; Pfundt, Rolph; de Brouwer, Arjan P; Veltman, Joris A; de Leeuw, Nicole; Wilson, Meredith; Antony, Jayne; Reitano, Santina; Luciano, Daniela; Fichera, Marco; Romano, Corrado; Brunner, Han G; Zuffardi, Orsetta; de Vries, Bert B A

    2010-02-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic features in these patients. In this study, we report the molecular and clinical characterisation of nine new 2q23.1 deletion patients and a clinical update on two previously reported patients. All patients were mentally retarded with pronounced speech delay and additional abnormalities including short stature, seizures, microcephaly and coarse facies. The majority of cases presented with stereotypic repetitive behaviour, a disturbed sleep pattern and a broad-based gait. These features led to the initial clinical impression of Angelman, Rett or Smith-Magenis syndromes in several patients. The overlapping 2q23.1 deletion region in all 15 patients comprises only one gene, namely, MBD5. Interestingly, MBD5 is a member of the methyl CpG-binding domain protein family, which also comprises MECP2, mutated in Rett's syndrome. Another gene in the 2q23.1 region, EPC2, was deleted in 12 patients who had a broader phenotype than those with a deletion of MBD5 only. EPC2 is a member of the polycomb protein family, involved in heterochromatin formation and might be involved in causing MR. Patients with a 2q23.1 microdeletion present with a variable phenotype and the diagnosis should be considered in mentally retarded children with coarse facies, seizures, disturbed sleeping patterns and additional specific behavioural problems.

  20. Order of six loci at 2q24-q31 and orientation of the HOXD locus

    SciTech Connect

    Rossi, E.; Floridia, G.; Zuffardi, O.

    1994-11-01

    HOXD, a gene cluster of 9 homeobox genes of the Antennapedia class: EVX2, a homeobox gene related to Drosophila-even-skipped gene; DLX1 and DLX2, two homeobox genes related to the Drosophila distal-less gene: and TTN and NEB, the genes for the two giant molecules titin and nebulin, both involved in the sarcomere structure, have been previously mapped to human 2q31-q32 and to mouse chromosome 2. They studied their relative order in human by applying FISH to three balanced chromosome rearrangements each with a breakpoint at 2q31. Unambiguous results led to mapping these genes and to orienting the HOXD locus along chromosome 2 according to the following order: cen, NEB, DLX1-DLX2-EVX2, HOXD (5{prime}-3{prime}), TTN, tel. All of these genes are part of a syntenic region covering 5-10 cM and conserved since the divergence of humans and rodents, and thus the same loci order should be present in mouse. FISH in metaphases of approximately 500 bands localized NEB to 2q24.1-124.2, while HOXD and TTN were localized to 2q31. 33 refs., 5 figs., 2 tabs.

  1. The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2

    SciTech Connect

    Tamimi, R.; Dyer-Montgomery, K.; Hernandez, R.; Tapscott, S.J.

    1996-06-15

    The Neurod gene is a basic-helix-loop-helix gene that regulates neurogenesis and is identical to the hamster beta2 gene that was cloned as a regulator of insulin transcription. Here we report the cloning of human NEUROD and mapping of the gene to human chromosome 2q32 and to mouse chromosome 2. 12 refs., 1 fig.

  2. 31 CFR 30.2 - Q-2: To what entities does this part apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Q-2: To what entities does this part apply? 30.2 Section 30.2 Money and Finance: Treasury Office of the Secretary of the Treasury TARP STANDARDS FOR COMPENSATION AND CORPORATE GOVERNANCE § 30.2 Q-2: To what entities does this part apply?...

  3. 2q37.3 Deletion Syndrome: Two Cases with Highly Distinctive Facial Phenotype, Discordant Association with Schizophrenic Psychosis, and Shared Deletion Breakpoint Region on 2q37.3.

    PubMed

    Mehraein, Yasmin; Pfob, Martina; Steinlein, Ortrud; Aichinger, Eric; Eggert, Marlene; Bubendorff, Valerie; Mannhart, Adelina; Müller, Stefan

    2015-01-01

    2q37.3 deletion syndrome belongs to the chromosomal 2q37 deletion spectrum which clinically resembles Albright hereditary osteodystrophy (AHO) syndrome. It is is mainly characterized by short stature, obesity, round face, brachydactyly type E, intellectual disability, behavioral problems, and variable intellectual deficits. Different from classical AHO syndrome, patients with 2q37 deletion syndrome lack renal parathyroid hormone resistance (pseudohypoparathyroidism) and soft tissue ossification. So far, deletion mapping or molecular breakpoint analyses of 2q37 have been performed in only few patients. Here, we report on 2 patients with 2q37.3 deletion syndrome. In both patients the breakpoint of the 5.5-Mb terminal microdeletion could be narrowed down to the same ∼ 200-kb interval on 2q37.3 by BAC-FISH and/or array-CGH. Flanking low-copy repeats may indicate a classical microdeletion syndrome genesis for the 2q37.3 microdeletion subgroup. Clinical evaluation revealed intellectual deficits and type E brachydactyly typical for classical AHO syndrome together with distinctive facial dysmorphisms not present in the former. Furthermore, one patient presented with schizophrenic psychosis, an observation that would be in accordance with previous reports about an association between schizophrenia susceptibility and an unknown gene within the chromosomal region 2q37.

  4. The human insulin receptor substrate-1 gene (IRS1) is localized on 2q36

    SciTech Connect

    Nishiyama, Masaki; Matsufuji, Senya; Hayashi, Shin-ichi; Furusaka, Akihiro; Tanaka, Teruji ); Inazawa, J.; Nakamura, Yusuke ); Ariyama, Takeshi ); Wands, J.R. )

    1994-03-01

    The chromosomal localization of some of the genes participating in the insulin signaling pathway is known. The insulin and insulin receptor genes have been mapped to chromosomes 11 and 19, respectively. To identify the chromosomal localization of the human IRS1 gene, the fluorescence in situ hybridization technique was employed with Genomic Clone B-10. A total of 50 metaphase cells exhibiting either single or double spots of hybridization signals were examined. Among them, 32 showed the specific signals on 2q36. Therefore, the authors assigned the human IRS1 gene to 2q36. The genes for homeobox sequence (HOX4), fibronectin 1, alkaline phosphatase (intestinal), transition protein 1, villin 1, collagen (type IV), Waardenburg syndrome (type 1), alanine-glyoxylate aminotransferase, and glucagon have been localized in the vicinity of the IRS1 gene.

  5. Neuropsychological profiles of patients with 2q37.3 deletion associated with developmental dyspraxia.

    PubMed

    Ogura, Kaeko; Takeshita, Kenzo; Arakawa, Chikako; Shimojima, Keiko; Yamamoto, Toshiyuki

    2014-12-01

    Patients with 2q37 deletions manifest brachydactyly mental retardation syndrome (BDMR). Recent advances in human molecular research have revealed that alterations in the histone deacetylase 4 gene (HDAC4) are responsible for the clinical manifestations of BDMR. Here, we report two male patients with 2q37.3 deletions. One of the patients showed a typical BDMR phenotype, and HDAC4 was included in the deletion region. HDAC4 was preserved in the other patient, and he showed a normal intelligence level with the delayed learning of complex motor skills. Detailed neuropsychological examinations revealed similar neuropsychological profiles in these two patients (visuo-spatial dyspraxia) that suggested developmental dyspraxia. These observations suggested that some other candidate genes for neuronal development exist in the telomeric region of HDAC4.

  6. Multiorgan autoimmunity in a Turner syndrome patient with partial monosomy 2q and trisomy 10p.

    PubMed

    Grossi, Armando; Palma, Alessia; Zanni, Ginevra; Novelli, Antonio; Loddo, Sara; Cappa, Marco; Fierabracci, Alessandra

    2013-02-25

    Turner syndrome is a condition caused by numeric and structural abnormalities of the X chromosome, and is characterized by a series of clinical features, the most common being short stature and gonadal dysgenesis. An increased frequency of autoimmune diseases as well as an elevated incidence of autoantibodies has been observed in Turner patients. We present a unique case of mosaic Turner syndrome with a complex rearrangement consisting of a partial deletion of chromosome 2q and duplication of chromosome 10p {[46],XX,der(2)t(2;10)(2pter→2q37::10p13→10pter)[127]/45,X,der(2)t(2;10)(2pter→2q37::10p13→10pter)[23]}. The patient is affected by partial empty sella, in association with a group of multiorgan autoimmunity-related manifestations including Hashimoto's thyroiditis, celiac disease, insulin-dependent diabetes mellitus (Type 1 diabetes, T1D), possible autoimmune inner ear disease with sensorineural deficit, preclinical Addison disease and alopecia universalis. The patient was previously described at the age of 2.4 years and now re-evaluated at the age of 14 years after she developed autoimmune conditions. AIRE gene screening revealed heterozygous c.834 C>G polymorphism (p.Ser278Arg) and IVS9+6G>A variation, thus likely excluding autoimmune polyendocrine syndrome Type 1 (APECED). Heterozygous R620W polymorphism of the protein tyrosine phosphatase non receptor type 22 (PTPN22) gene was detected in patient's DNA. SNP-array analysis revealed that autoimmunity-related genes could be affected by the partial monosomy 2q and trisomy 10p. These data suggest that early genetic analysis in TS patients with complex associations of multiorgan autoimmune manifestations would permit a precise diagnostic classification and also be an indicator for undiscovered pathogenetic mechanisms.

  7. The Human Epilepsy Mutation GABRG2(Q390X) Causes Chronic Subunit Accumulation and Neurodegeneration

    PubMed Central

    Kang, Jing-Qiong; Shen, Wangzhen; Zhou, Chengwen; Xu, Dong; Macdonald, Robert L.

    2015-01-01

    Genetic epilepsy and neurodegenerative diseases are two common neurological disorders conventionally viewed as being unrelated. A subset of patients with severe genetic epilepsies with impaired development and often death respond poorly to anticonvulsant drug therapy, suggesting a need for new therapeutic targets. Previously, we reported that multiple GABAA receptor epilepsy mutations caused protein misfolding and abnormal receptor trafficking. Here we establish in a novel model of a severe human genetic epileptic encephalopathy, the Gabrg2+/Q390X knock-in mouse, that in addition to impairing inhibitory neurotransmission, mutant GABAA receptor γ2(Q390X) subunits accumulated and aggregated intracellularly, activated caspase 3 and caused widespread, age-dependent neurodegeneration. These novel findings suggest that the fundamental protein metabolism and cellular consequences of the epilepsy-associated mutant γ2(Q390X) ion channel subunit are not fundamentally different from those associated with neurodegeneration. The study has far-reaching significance for identification of conserved pathological cascades and mechanism-based therapies that overlap genetic epilepsies and neurodegenerative diseases. PMID:26005849

  8. Critical region in 2q31.2q32.3 deletion syndrome: Report of two phenotypically distinct patients, one with an additional deletion in Alagille syndrome region

    PubMed Central

    2012-01-01

    Background Standard cytogenetic analysis has revealed to date more than 30 reported cases presenting interstitial deletions involving region 2q31-q32, but with poorly defined breakpoints. After the postulation of 2q31.2q32.3 deletion as a clinically recognizable disorder, more patients were reported with a critical region proposed and candidate genes pointed out. Results We report two female patients with de novo chromosome 2 cytogenetically visible deletions, one of them with an additional de novo deletion in chromosome 20p12.2p12.3. Patient I presents a 16.8 Mb deletion in 2q31.2q32.3 while patient II presents a smaller deletion of 7 Mb in 2q32.1q32.3, entirely contained within patient I deleted region, and a second 4 Mb deletion in Alagille syndrome region. Patient I clearly manifests symptoms associated with the 2q31.2q32.3 deletion syndrome, like the muscular phenotype and behavioral problems, while patient II phenotype is compatible with the 20p12 deletion since she manifests problems at the cardiac level, without significant dysmorphisms and an apparently normal psychomotor development. Conclusions Whereas Alagille syndrome is a well characterized condition mainly caused by haploinsufficiency of JAG1 gene, with manifestations that can range from slight clinical findings to major symptoms in different domains, the 2q31.2q32.3 deletion syndrome is still being delineated. The occurrence of both imbalances in reported patient II would be expected to cause a more severe phenotype compared to the individual phenotype associated with each imbalance, which is not the case, since there are no manifestations due to the 2q32 deletion. This, together with the fact that patient I deleted region overlaps previously reported cases and patient II deletion is outside this common region, reinforces the existence of a critical region in 2q31.3q32.1, between 181 to 185 Mb, responsible for the clinical phenotype. PMID:22550961

  9. Interstitial deletion 6q16.2q22.2 in a child with ectrodactyly.

    PubMed

    Correa-Cerro, L; Garcíaz-Cruz, D; Díaz-Castaños, L; Figuera, L E; Sanchez-Corona, J

    1996-01-01

    A boy of 16 months of age with psychomotor retardation, short stature, microbrachycephaly, triangular face, microphthalmia, palpebral fissures slanted downward, cardiopathy, simian crease on left hand, agenesis of fourth finger on the right hand and of the nail in the second finger on the right one was studied. The karyotype showed a complement of 46, XY, del(6) (q16.2q22.2). The clinical and cytogenetic analysis with other previous cases described in the literature led us to identificate other patients with ectrodactyly. Therefore as other authors we suggest the possible localization of gene(s) that could have involvement with the development of extremities in this segment.

  10. De novo interstitial deletion q16.2q21 on chromosome 6

    SciTech Connect

    Villa, A.; Urioste, M.; Luisa, M.

    1995-01-30

    A de novo interstitial deletion of 6q16.2q21 was observed in a 23-month-old boy with mental and psychomotor delay, obese appearance, minor craniofacial anomalies, and brain anomalies. We compare clinical manifestations of this patient with those observed in previously reported cases with similar 6q interstitial deletions. It is interesting to note the clinical similarities between some patients with interstitial deletions of 6q16 or q21 bands and patients with Prader-Willi syndrome (PWS) and it may help to keep in mind cytogenetic studies of patients with some PWS findings. 24 refs., 3 figs., 2 tabs.

  11. Self-density frequency shift measurements of Raman N 2 Q-branch transitions

    NASA Astrophysics Data System (ADS)

    Lavorel, B.; Chaux, R.; Saint-Loup, R.; Berger, H.

    1987-04-01

    We report stimulated Raman investigations of N 2 Q-branch transitions in view to measure the self-density frequency shift. These measurements performed at 295 K over the density range 0.02-0.8 Amagat lead to a mean shift value equal to -5.5×10 -3 cm -1/Amagat. Moreover, our data extrapolated at zero density allowed new refinements of the N 2 molecular constants: v0=2329.91165 (17) cm -1, B1- B0=-0.0173714 (22) cm -1 and D1- D0=(7.6±5.0)×10 -9 cm -1.

  12. Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).

    PubMed

    Ishikiriyama, S; Tonoki, H; Shibuya, Y; Chin, S; Harada, N; Abe, K; Niikawa, N

    1989-08-01

    We report on a child with Waardenburg syndrome type I and a paracentric inversion of chromosome 2. This 20 month-old boy has dystopia canthorum, sensorineural deafness, heterochromia iridis, partially albinotic ocular fundi, and partial leukodermia. He does not have mental retardation or any skeletal abnormalities. Family history was unremarkable. Cytogenetic studies demonstrated that the patient has a paracentric inversion (2)(q35q37.3); his parents have normal chromosomes. These findings suggest that the locus of the gene for Waardenburg syndrome type I may be at 2q35 or 2q37.3.

  13. The Born-Oppenheimer approach to the heavy q 2q¯ 2 system

    NASA Astrophysics Data System (ADS)

    Osamu, Morimatsu

    1989-12-01

    The Born-Oppenheimer approach is applied to the heavy q 2q¯ 2 system in the hamiltonian formulation of lattice QCD. This is done first in the adiabatic approximation and then in terms of coupled channels. The strong coupling expansion is employed in order to study explicitly the behavior of the q 2q¯ 2 system in the confining phase. In both cases the obtained equation can be interpreted as an effective Schrödinger equation for fermions. In the adiabatic approximation the equation is equivalent to a potential model without color and the obtained potential is a many-body potential of flip-flop type with short-range attraction. While in coupled channels the equation is similar to a potential model with color, however the overlap of two states, corresponding to two possible arrangements of fermions in qq¯ pairs, includes the additional contribution from the overlap of the gluon field in two states. The overlap and the transition potential of these two states damp off exponentially as the separation of two qq¯ pairs increases. In both cases these results imply short-range attraction between mesons. In coupled channels the interaction between mesons tends to vanish as the number of colors increases.

  14. Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13.

    PubMed Central

    Cannizzaro, L A; Croce, C M; Griffin, C A; Simeone, A; Boncinelli, E; Huebner, K

    1987-01-01

    Four human homeo box-containing cDNAs isolated from mRNA of an SV40-transformed human fibroblast cell line have been regionally localized on the human gene map. One cDNA clone, c10, was found to be nearly identical to the previously mapped Hox-2.1 gene at 17q21. A second cDNA clone, c1, which is 87% homologous to Hox-2.2 at the nucleotide level but is distinct from Hox-2.1 and Hox-2.2, also maps to this region of human chromosome 17 and is probably another member of the Hox-2 cluster of homeo box-containing genes. The third cDNA clone, c8, in which the homeo box is approximately 84% homologous to the mouse Hox-1.1 homeo box region on mouse chromosome 6, maps to chromosome region 12q12----12q13, a region that is involved in chromosome abnormalities in human seminomas and teratomas. The fourth cDNA clone, c13, whose homeo box is approximately 73% homologous to the Hox-2.2 homeo box sequence, is located at chromosome region 2q31----q37. The human homeo box-containing cluster of genes at chromosome region 17q21 is the human cognate of the mouse homeo box-containing gene cluster on mouse chromosome 11. Other mouse homeo box-containing genes of the Antennapedia class (class I) map to mouse chromosomes 6 (Hox-1, proximal to the IgK locus) and 15 (Hox-3). A mouse gene, En-1, with an engrailed-like homeo box (class II) and flanking region maps to mouse chromosome 1 (near the dominant hemimelia gene). Neither of the class I homeo box-containing genes--c8 and c13--maps to a region of obvious homology to chromosomal positions of the presently known mouse homeo box-containing genes. Images Fig. 2 Fig. 3 Fig. 5 PMID:2886047

  15. The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11. 2-q12

    SciTech Connect

    Ramsay, M.; Colman, M.A.; Stevens, G.; Zwane, E.; Kromberg, J.; Jenkins, T. ); Garral, M.

    1992-10-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous. 43 refs., 2 figs., 1 tab.

  16. A gene for familial paroxysmal dyskinesia (FPD1) maps to chromosome 2q

    SciTech Connect

    Fouad, G.T.; Durcan, S.; Ptacek, L.J.

    1996-07-01

    Dyskinesias are hyperkinetic and involuntary movements that may result from any of a number of different genetic, infectious, and drug-induced causes. Some of the hereditary dyskinetic syndromes are characterized by paroxysmal onset of the abnormal movements. The classification of the familial paroxysmal dyskinesias (FPD) recognizes several distinct, although overlapping, phenotypes. Different forms of the disorder include attacks that are (1) induced by sudden movement (kinesiogenic); (2) spontaneous (non-kinesiogenic); and (3) induced by prolonged periods of exertion. Linkage analysis was pursued in a family segregating an autosomal dominant allele for non-kinesiogenic FPD. The disease allele was mapped to a locus on chromosome 2q31-36 (LOD score 4.64, {theta} = 0). Identification of distinct genetic loci for the paroxysmal dyskinesias will lead to a new genetic classification and to better understanding of these disorders. 26 refs., 2 figs., 1 tab.

  17. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson's Disease Locus.

    PubMed

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M; Heckman, Michael G; McCarthy, Allan; Soto-Ortolaza, Alexandra I; Walton, Ronald L; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W; Uitti, Ryan J; Wszolek, Zbigniew K; Ross, Owen A

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson's disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11-1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.

  18. Deletion 2q37.3 and autism: molecular cytogenetic mapping of the candidate region for autistic disorder.

    PubMed

    Lukusa, T; Vermeesch, J R; Holvoet, M; Fryns, J P; Devriendt, K

    2004-01-01

    Fine mapping of deletion regions in autistic patients represents a valuable screening tool for identifying candidate genes for autism. A number of studies have ascertained associations between autism and terminal 2q deletion with the breakpoint within 2q37. Here we describe a 12-year-old female patient with terminal 2q37.3 cryptic deletion and autistic behaviour. Her clinical features included hypotonia and feeding difficulties during infancy, coarse face with notably prominent forehead, prominent eyebrows, broad flat nasal bridge and round cheeks, small hands and feet with bilateral brachymetaphalangism, proximal implantation of the thumbs and short toenails, mild mental retardation and autistic behaviour. Recorded autistic features included early lack of eye contact and, during infancy, little social interactions, propensity to be stereotypically busy and to get anxious. In order to more closely delineate the linkage region for autism within 2q37, the findings in this patient were combined to those in 2 previously reported siblings with a well documented 2q37.3 deletion, but without autistic disorder. The exact size of the deleted segment was determined by mapping the deleted region in each group with a series of specific BAC clones linearly ordered on the 2q37 region. The deletion in the autistic patient appeared to be larger [breakpoint flanked by more centromeric clones RP11-680016 (236.9 Mb) and 201F21 (237.4 Mb)] than in the non autistic siblings [more telomeric clones RP11-205L13 (237.8 Mb) and 346114 (238.2 Mb)], revealing a distance of maximum 1.3 Mb between the breakpoints. Accordingly, the extent of the candidate region for susceptibility genes for autism on distal 2q is reduced to maximum 1.3 Mb. Comparison with another well documented autistic patient from the literature results in the same conclusion. These findings represent thus a further step towards identifying genes predisposing to autism.

  19. Regional assignment of the human homebox-containing gene EN1 to chromosome 2q13-q21

    SciTech Connect

    Koehler, A.; Muenke, M. ); Logan, C. ); Joyner, A.L. Samuel Lunenfeld Research Institute, Toronto )

    1993-01-01

    The human homeobox-containing genes EN1 and EN2 are closely related to the Drosophila pattern formation gene engrailed (en), which may be important in brain development, as shown by gene expression studies during mouse embryogenesis. Here, we have refined the localization of EN1 to human chromosome 2q13-q21 using a mapping panel of rodent/human cell hybrids containing different regions of chromosome 2 and a lymphoblastoid cell line with an interstitial deletion, del(2) (q21-q23.2). This regional assignment of EN1 increases to 22 the number of currently known genes on human chromosome 2q that have homologs on the proximal region of mouse chromosome 1. 15 refs., 2 figs.

  20. Investigation of TBR1 Hemizygosity: Four Individuals with 2q24 Microdeletions

    PubMed Central

    Traylor, R.N.; Dobyns, W.B.; Rosenfeld, J.A.; Wheeler, P.; Spence, J.E.; Bandholz, A.M.; Bawle, E.V.; Carmany, E.P.; Powell, C.M.; Hudson, B.; Schultz, R.A.; Shaffer, L.G.; Ballif, B.C.

    2012-01-01

    TBR1 encodes a transcription factor with critical roles in corticogenesis, including cortical neuron migration and axon pathfinding, establishment of regional and laminar identity of cortical neurons, and control of glutamatergic neuronal cell fate. Based upon TBR1's role in cortical development, we sought to investigate TBR1 hemizygosity in individuals referred for genetic evaluation of intellectual disability and developmental delay. We describe 4 patients with microdeletions identified by molecular cytogenetic techniques, encompassing TBR1 and spanning 2q24.1q31.1, ranging in size from 2.17 to 12.34 Mb. Only the patient with the largest deletion had a possible cortical malformation. Mild ventriculomegaly is the only common brain anomaly, present in all patients; a Chiari I malformation is seen in 2 patients, and mega cisterna magna is seen in a third. Our findings are consistent with Tbr1 mouse models showing that hemizygosity of the gene requires additional genetic factors for the manifestation of severe structural brain malformations. Other syndromic features are present in these patients, including autism spectrum disorders, ocular colobomas, and craniosynostosis, features that are likely affected by the deletion of genes other than TBR1. PMID:23112752

  1. Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer

    PubMed Central

    Henrion, Marc; Frampton, Matthew; Scelo, Ghislaine; Purdue, Mark; Ye, Yuanqing; Broderick, Peter; Ritchie, Alastair; Kaplan, Richard; Meade, Angela; McKay, James; Johansson, Mattias; Lathrop, Mark; Larkin, James; Rothman, Nathaniel; Wang, Zhaoming; Chow, Wong-Ho; Stevens, Victoria L.; Ryan Diver, W.; Gapstur, Susan M.; Albanes, Demetrius; Virtamo, Jarmo; Wu, Xifeng; Brennan, Paul; Chanock, Stephen; Eisen, Timothy; Houlston, Richard S.

    2013-01-01

    Genome-wide association studies (GWASs) of renal cell cancer (RCC) have identified four susceptibility loci thus far. To identify an additional RCC common susceptibility locus, we conducted a GWAS and performed a meta-analysis with published GWASs (totalling 2215 cases and 8566 controls of European background) and followed up the most significant association signals [nine single nucleotide polymorphisms (SNPs) in eight genomic regions] in 3739 cases and 8786 controls. A combined analysis identified a novel susceptibility locus mapping to 2q22.3 marked by rs12105918 (P = 1.80 × 10−8; odds ratio 1.29, 95% CI: 1.18–1.41). The signal localizes to intron 2 of the ZEB2 gene (zinc finger E box-binding homeobox 2). Our findings suggest that genetic variation in ZEB2 influences the risk of RCC. This finding provides further insights into the genetic and biological basis of inherited genetic susceptibility to RCC. PMID:23184150

  2. Chromosome 2q31.1 Associates with ESRD in Women with Type 1 Diabetes

    PubMed Central

    Sandholm, Niina; McKnight, Amy Jayne; Salem, Rany M.; Brennan, Eoin P.; Forsblom, Carol; Harjutsalo, Valma; Mäkinen, Ville-Petteri; McKay, Gareth J.; Sadlier, Denise M.; Williams, Winfred W.; Martin, Finian; Panduru, Nicolae Mircea; Tarnow, Lise; Tuomilehto, Jaakko; Tryggvason, Karl; Zerbini, Gianpaolo; Comeau, Mary E.; Langefeld, Carl D.; Godson, Catherine; Hirschhorn, Joel N.; Maxwell, Alexander P.; Florez, Jose C.

    2013-01-01

    Sex and genetic variation influence the risk of developing diabetic nephropathy and ESRD in patients with type 1 diabetes. We performed a genome-wide association study in a cohort of 3652 patients from the Finnish Diabetic Nephropathy (FinnDiane) Study with type 1 diabetes to determine whether sex-specific genetic risk factors for ESRD exist. A common variant, rs4972593 on chromosome 2q31.1, was associated with ESRD in women (P<5×10−8) but not in men (P=0.77). This association was replicated in the meta-analysis of three independent type 1 diabetes cohorts (P=0.02) and remained significant for women (P<5×10−8; odds ratio, 1.81 [95% confidence interval, 1.47 to 2.24]) upon combined meta-analysis of the discovery and replication cohorts. rs4972593 is located between the genes that code for the Sp3 transcription factor, which interacts directly with estrogen receptor α and regulates the expression of genes linked to glomerular function and the pathogenesis of nephropathy, and the CDCA7 transcription factor, which regulates cell proliferation. Further examination revealed potential transcription factor–binding sites within rs4972593 and predicted eight estrogen-responsive elements within 5 kb of this locus. Moreover, we found sex-specific differences in the glomerular expression levels of SP3 (P=0.004). Overall, these results suggest that rs4972593 is a sex-specific genetic variant associated with ESRD in patients with type 1 diabetes and may underlie the sex-specific protection against ESRD. PMID:24029427

  3. A Quantitative Electrophysiological Biomarker of Duplication 15q11.2-q13.1 Syndrome

    PubMed Central

    Frohlich, Joel; Senturk, Damla; Saravanapandian, Vidya; Golshani, Peyman; Reiter, Lawrence T.; Sankar, Raman; Thibert, Ronald L.; DiStefano, Charlotte; Huberty, Scott; Cook, Edwin H.; Jeste, Shafali S.

    2016-01-01

    Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12–20 Hz) and beta2 (20–30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1–4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome. PMID:27977700

  4. PB2-Q591K Mutation Determines the Pathogenicity of Avian H9N2 Influenza Viruses for Mammalian Species

    PubMed Central

    Wang, Congrong; Lee, Horace Hok Yeung; Yang, Zi Feng; Mok, Chris Ka Pun; Zhang, Zhi

    2016-01-01

    Background Influenza A subtype H9N2 is widespread and prevalent in poultry. It has repeatedly transmitted zoonotically to cause mild influenza-like illness in humans and is regarded as a potential pandemic candidate. In additon, the six internal genes of H7N9 and H10N8 viruses which caused infection in human in China as well as some of the highly pathogenic H5N1 strains are origined from H9N2. Previous studies have shown that the mammalian adaptation PB2-Q591K contributes to the pathogenicity of H5N1 and H7N9 viruses. However, the role of the PB2-Q591K mutation in H9N2 subtype is still not well understood. Methods To define and compare the individual role of PB2-Q591K substitution in the PB2 gene segment of H9N2 in relation to polymerase activity, replication competence and the pathogenicity using in vitro and in vivo models. Results The PB2-Q591K mutation in H9N2 virus enhanced the polymerase activity and virus replication in human NHBE cells when compared to the wild type strain. Mice infected with the PB2 mutant showed significant weight loss, higher virus replication and immune responses in the lungs. Conclusions Our evidences suggest that the PB2-Q591K, in addition to the -E627K mutation in H9N2 enhanced the pathogenicity in mammalian host. PMID:27684944

  5. Angelman syndrome and severe infections in a patient with de novo 15q11.2-q13.1 deletion and maternally inherited 2q21.3 microdeletion.

    PubMed

    Neubert, Gerda; von Au, Katja; Drossel, Katrin; Tzschach, Andreas; Horn, Denise; Nickel, Renate; Kaindl, Angela M

    2013-01-10

    Angelman syndrome is a neurodevelopmental disorder characterized by mental retardation, severe speech disorder, facial dysmorphism, secondary microcephaly, ataxia, seizures, and abnormal behaviors such as easily provoked laughter. It is most frequently caused by a de novo maternal deletion of chromosome 15q11-q13 (about 70-90%), but can also be caused by paternal uniparental disomy of chromosome 15q11-q13 (3-7%), an imprinting defect (2-4%) or in mutations in the ubiquitin protein ligase E3A gene UBE3A mostly leading to frame shift mutation. In addition, for patients with overlapping clinical features (Angelman-like syndrome), mutations in methyl-CpG binding protein 2 gene MECP2 and cyclin-dependent kinase-like 5 gene CDKL5 as well as a microdeletion of 2q23.1 including the methyl-CpG binding domain protein 5 gene MBD5 have been described. Here, we describe a patient who carries a de novo 5Mb-deletion of chromosome 15q11.2-q13.1 known to be associated with Angelman syndrome and a further, maternally inherited deletion 2q21.3 (~364kb) of unknown significance. In addition to classic features of Angelman syndrome, she presented with severe infections in the first year of life, a symptom that has not been described in patients with Angelman syndrome. The 15q11.2-q13.1 deletion contains genes critical for Prader-Willi syndrome, the Angelman syndrome causing genes UBE3A and ATP10A/C, and several non-imprinted genes: GABRB3 and GABRA5 (both encoding subunits of GABA A receptor), GOLGA6L2, HERC2 and OCA2 (associated with oculocutaneous albinism II). The deletion 2q21.3 includes exons of the genes RAB3GAP1 (associated with Warburg Micro syndrome) and ZRANB3 (not disease-associated). Despite the normal phenotype of the mother, the relevance of the 2q21.3 microdeletion for the phenotype of the patient cannot be excluded, and further case reports will need to address this point.

  6. Characterization of redox states of Ru(OH(2))(Q)(tpy)(2+) (Q = 3,5-di-tert-butyl-1,2-benzoquinone, tpy = 2,2':6',2''-terpyridine) and related species through experimental and theoretical studies.

    PubMed

    Tsai, Ming-Kang; Rochford, Jonathan; Polyansky, Dmitry E; Wada, Tohru; Tanaka, Koji; Fujita, Etsuko; Muckerman, James T

    2009-05-18

    The redox states of Ru(OH(2))(Q)(tpy)(2+) (Q = 3,5-di-tert-butyl-1,2-benzoquinone, tpy = 2,2':6',2''-terpyridine) are investigated through experimental and theoretical UV-vis spectra and Pourbaix diagrams. The electrochemical properties are reported for the species resulting from deprotonation and redox processes in aqueous solution. The formal oxidation states of the redox couples in the various intermediate complexes are systematically assigned using electronic structure theory. The controversy over the electronic assignment of ferromagnetic vs. antiferromagnetic coupling is investigated through comparison of ab initio methods and the broken-symmetry density functional theory (DFT) approach. The various pK(a) values and reduction potentials, including the consideration of proton-coupled electron-transfer (PCET) processes, are calculated, and the theoretical version of the Pourbaix diagram is constructed in order to elucidate and assign several previously ambiguous regions in the experimental diagram.

  7. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    PubMed Central

    Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  8. Autistic and Rett-like features associated with 2q33.3-q34 interstitial deletion.

    PubMed

    Jang, Dae-Hyun; Chae, Hyojin; Kim, Myungshin

    2015-09-01

    We describe the fourth reported case of a de novo 2q33.3-q34 interstitial deletion and review the literature in attempt to identify relevant candidate genes. A 15-month-old female patient presented for evaluation with poor eye contact and developmental delay. She had microcephaly and mild dysmorphic features, such as downslanting palpebral fissures, high forehead, small mouth, high palate, and general hypotonia. At 30 months of age, she was referred to the genetic clinic for an evaluation of persistent developmental delay, autistic traits, and Rett-like features, including bruxism and repetitive movement of the left hand. Chromosome analysis revealed 46,XX at the 550 band level. No abnormalities were found on analysis of MECP2 gene for Rett syndrome and a DNA methylation test for Prader-Willi syndrome. An array comparative genomic hybridization analysis revealed a de novo 2q33.3-q34 heterozygous deletion (206,048,173-211,980,867). The deletion was estimated to be 5.9 Mb in size and contained 34 known genes. Candidate genes were identified as NRP2, ADAM23, KLF7, CREB1, MAP2, UNC80, and LANCL1 for the 2q33.3-q34 interstitial deletion.

  9. A familial GLI2 deletion (2q14.2) not associated with the holoprosencephaly syndrome phenotype.

    PubMed

    Kordaß, Ulrike; Schröder, Carmen; Elbracht, Miriam; Soellner, Lukas; Eggermann, Thomas

    2015-05-01

    Molecular alterations of the GLI2 gene in 2q14.2 are associated with features from the holoprosencephaly spectrum. However, the phenotype is extremely variable, ranging from unaffected mutation heterozygotes to isolated or combined pituitary hormone deficiency, and to patients with a phenotype that overlaps with holoprosencephaly, including abnormal pituitary gland formation/function, craniofacial dysmorphisms, branchial arch anomalies, and polydactyly. Although many point mutations within the GLI2 gene have been identified, large (sub) microscopic deletions affecting 2q14.2 are rare. We report on a family with a 4.3 Mb deletion in 2q14 affecting GLI2 without any dysmorphologic features belonging to the holoprosencephaly spectrum. This family confirms the incomplete penetrance of genomic disturbances affecting the GLI2 gene. However, the family presented here is unique as none of the three identified individuals with a GLI2 deletion showed any typical signs of holoprosencephaly, whereas all patients reported so far were referred for genetic testing because at least one member exhibited holoprosencephaly and related features.

  10. Delineation of 2q32q35 Deletion Phenotypes: Two Apparent “Proximal” and “Distal” Syndromes

    PubMed Central

    Taylor, Juliet; Gregersen, Nerine; George, Alice M.; Love, Donald R.

    2013-01-01

    We report on three patients with interstitial deletions of the long arm of chromosome 2 involving bands 2q32.1–q35. They presented with wide-ranging phenotypic variation including facial dysmorphisms, cleft palate, learning difficulties, behavioural issues and severe heart defects. Microarray analysis confirmed an 8.6 Mb deletion in patients 1 and 2 and a 24.7 Mb deletion in patient 3. We discuss the genes involved in the deleted regions including MYO1B, GLS, FRZB, SATB2, and CPS1 and compare the phenotype with those reported in the literature. Taken together, these data suggest that there is a spectrum of disease severity such that patients with deletions encompassing the region of 2q32.1q32.2, which includes the FRZB gene, show an apparently milder phenotype compared to those that lie further distal in 2q32.3q35 that encompasses the SATB2 gene. PMID:23840981

  11. Partial trisomy 2q due to a maternal balanced translocation t(2;22) (q31;p12)

    SciTech Connect

    Steinberg, L.S.; Bleiman, M.; Punnett, H.H.

    1994-09-01

    Features consistent among reported patients with 2q duplications due to familial translocations or de novo duplications include pre- and postnatal growth failure, ocular defects such as congenital glaucoma, cardiac defects, micrognathia, urogenital defects, renal defects, connective tissue laxity, neurologic defects, and dermatologic abnormalities. Genotype/phenotype correlations of patients with trisomy 2q due to familial translocations are complicated by the presence of the deletions of the other chromosome involved. We have had the opportunity to observe `pure` trisomy 2q31-qter resulting from adjacent-1 segregation from 46,XX,t(2;22)(q31;p12) in a carrier mother with apparent loss of the 22 NOR region. He was the 2453 gm product of a gestation complicated by gestational diabetes to a 29-year-old G1 P0 mother and a 30-year-old father. At birth, he was noted to have hypotonia, micrognathia, microphthalmia, left cryptorchidism, hypospadias, bilateral clinodactyly of the fifth digits, mild hyperextensibility of the joints, dry skin disorder, and bilateral hydronephrosis by ultrasound. He was treated for hypoglycemia in the nursery and had a vesicostomy at two months for vesicoureteral reflux. A hearing test at two months found moderate hearing loss in the right ear and mild to moderate hearing loss in the left ear. At 3 months he had surgery for a PDA and bilateral glaucoma and was treated for periods of hypothermia and type IV renal tubular acidosis. This patient and others with unbalanced translocations involving the NOR region of an acrocentric chromosome allow for genotype/phenotype correlation of the `pure` trisomic region.

  12. Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

    PubMed

    Tabassum, Rubina; Chauhan, Ganesh; Dwivedi, Om Prakash; Mahajan, Anubha; Jaiswal, Alok; Kaur, Ismeet; Bandesh, Khushdeep; Singh, Tejbir; Mathai, Benan John; Pandey, Yogesh; Chidambaram, Manickam; Sharma, Amitabh; Chavali, Sreenivas; Sengupta, Shantanu; Ramakrishnan, Lakshmi; Venkatesh, Pradeep; Aggarwal, Sanjay K; Ghosh, Saurabh; Prabhakaran, Dorairaj; Srinath, Reddy K; Saxena, Madhukar; Banerjee, Monisha; Mathur, Sandeep; Bhansali, Anil; Shah, Viral N; Madhu, Sri Venkata; Marwaha, Raman K; Basu, Analabha; Scaria, Vinod; McCarthy, Mark I; Venkatesan, Radha; Mohan, Viswanathan; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2013-03-01

    Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.

  13. Partial trisomy 22 (q11.2-q13.1) as a result of duplication and pericentric inversion.

    PubMed Central

    Prasher, V P; Roberts, E; Norman, A; Butler, A C; Krishnan, V H; McMullan, D J

    1995-01-01

    A case of a 27 year old male with a duplication of part of the long arm of chromosome 22 (22q11.2-q13.1) together with a pericentric inversion of the same chromosome is reported. Particular phenotypic features of note include absence of speech, persistent self-injury, lack of daily living skills, colobomata, and very poor vision. Similarities between this case and other case reports of duplications of the long arm of chromosome 22 are discussed. Images PMID:7643363

  14. Duplication at chromosome 2q31.1-q31.2 in a family presenting syndactyly and nystagmus.

    PubMed

    Ghoumid, Jamal; Andrieux, Joris; Sablonnière, Bernard; Odent, Sylvie; Philippe, Nathalie; Zanlonghi, Xavier; Saugier-Veber, Pascale; Bardyn, Thomas; Manouvrier-Hanu, Sylvie; Holder-Espinasse, Muriel

    2011-11-01

    HOXD genes encode transcription factors involved in the antero-posterior patterning of the limb bud and in the specification of fingers. During the embryo development, HOXD genes are expressed, following a spatio-temporal colinearity that involves at least three regions, centrometric and telomeric to this cluster. Here, we describe a father and a daughter presenting a 3-4 hand bilateral syndactyly associated with a nystagmus. Array-comparative genomic hybridisation showed a 3.8 Mb duplication at 2q31.1-q31.2, comprising 27 genes including the entire HOXD cluster. We performed expression studies in lymphoblasts by reverse transcription-PCR and observed an HOXD13 and HOXD10 overexpression, whereas the HOXD12 expression was decreased. HOXD13 and HOXD10 overexpression, associated with a misregulation of at least HOXD12, may therefore induce the syndactyly. Deletions of the HOXD cluster and its regulatory sequences induce hand malformations and, particularly, finger anomalies. Recently, smaller duplications of the same region have been reported in association with a mesomelic dysplasia, type Kantaputra. We discuss the variable phenotypes associated with such 2q duplications.

  15. The Comorbidity of Autism with the Genomic Disorders of Chromosome 15q11.2-q13

    PubMed Central

    Hogart, Amber; Wu, David; LaSalle, Janine M.; Schanen, N. Carolyn

    2010-01-01

    A cluster of low copy repeats on the proximal long arm of chromosome 15 mediate various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that increased copy number of maternally derived alleles contributes to autism susceptibility. Notably, nonimprinted, biallellically expressed genes within the interval also have been shown to be misexpressed in brains of patients with chromosome 15q11.2-q13 genomic disorders, indicating that they also likely play a role in the phenotypic outcome. This review provides an overview of the phenotypes of these disorders and their relationships with ASD and outlines the regional genes that may contribute to the autism susceptibility imparted by copy number variation of the region. PMID:18840528

  16. Localization of a novel gene for congenital nonsyndromic simple microphthalmia to chromosome 2q11-14.

    PubMed

    Li, Hui; Wang, Jia-Xin; Wang, Cheng-Ye; Yu, Ping; Zhou, Qiang; Chen, Yong-Gang; Zhao, Lu-Hang; Zhang, Ya-Ping

    2008-01-01

    Microphthalmia is a clinically and genetically heterogeneous disorder of eye development. The genetic basis of nonsyndromic microphthalmia is not yet fully understood. Previous studies indicated that disease pedigrees from different genetic backgrounds could be attributed to completely different gene loci. To investigate the etiology in a large autosomal-dominant inherited simple microphthalmia (nanophthalmia) pedigree, which is the first genetically analyzed Chinese microphthalmia pedigree, we performed a whole-genome scan using 382 micro-satellite DNA markers after the exclusion of reported candidates associated with microphthalmia. Strong evidence indicated that microphthalmia in this family was mapped to an unreported new locus on chromosome 2q. A significantly positive two-point LOD score was obtained with a maximum 3.290 at a recombination fraction of 0.00 for marker D2S2265. Subsequent haplotype analysis and recombination data further confined the disease-causing gene to a 15-cM interval between D2S1890 and D2S347 on 2q11-14. Our results further underlined the degree of heterogeneity in microphthalmia from Chinese background and localized a novel gene which regulates eye embryogenesis.

  17. HYDRAULIC CONDUCTIVITY OF SALTSTONE FORMULATED USING 1Q11, 2Q11 AND 3Q11 TANK 50 SLURRY SAMPLES

    SciTech Connect

    Reigel, M.; Nichols, R.

    2012-06-27

    As part of the Saltstone formulation work requested by Waste Solidification Engineering (WSE), Savannah River National Laboratory (SRNL) was tasked with preparing Saltstone samples for fresh property analysis and hydraulic conductivity measurements using actual Tank 50 salt solution rather than simulated salt solution. Samples of low level waste salt solution collected from Tank 50H during the first, second, and third quarters of 2011 were used to formulate the Saltstone samples. The salt solution was mixed with premix (45 wt % slag, 45 wt % fly ash, and 10 wt % cement), in a ratio consistent with facility operating conditions during the quarter of interest. The fresh properties (gel, set, bleed) of each mix were evaluated and compared to the recommended acceptance criteria for the Saltstone Production Facility. ASTM D5084-03, Method C was used to measure the hydraulic conductivity of the Saltstone samples. The hydraulic conductivity of Saltstone samples prepared from 1Q11 and 2Q11 samples of Tank 50H is 4.2E-9 cm/sec and 2.6E-9 cm/sec, respectively. Two additional 2Q11 and one 3Q11 sample were not successfully tested due to the inability to achieve stable readings during saturation and testing. The hydraulic conductivity of the samples made from Tank 50H salt solution compare well to samples prepared with simulated salt solution and cured under similar conditions (1.4E-9 - 4.9E-8 cm/sec).

  18. Infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations.

    PubMed

    Riikonen, Raili Sylvia; Wallden, Tiina; Kokkonen, Hannaleena

    2016-01-01

    Familial cases of West syndrome have been reported only in Japan. In that study no chromosomal analyses were made. It has been suggested that microarray analysis should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We report here the first case of infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. The daughter and mother with infantile spasms, and the autistic son had the duplication. The clinical course of infantile spasms was very similar in the mother and daughter. The spasms were primarily considered to be of unknown aetiology. Chromosomal microarray analysis revealed a 6.2 Mb size 15q11.2q13.1 duplication. The duplication belongs to the 15q11q13 duplication syndrome (OMIM 608636) which when maternally derived is characterised by neuro-behavioural disorders like autism, hypotonia, cognitive deficit, language delay and epilepsy. The proportion of patients with unknown aetiology for infantile spasms will decrease when more careful chromosomal studies are made. Our report expands the phenotype of chromosome 15q duplication syndrome and is the first report of this abnormality in two successive generations of infantile spasms.

  19. Terminal deletion of the long arm of chromosome 2 in a premature infant with karyotype: 46,XY, del(2)(q37)

    SciTech Connect

    Wang, T.H.; Johnston, K.; Hsieh, C.L.; Dennery, P.A.

    1994-02-15

    The authors present a premature newborn boy with multiple congenital anomalies, including craniofacial anomalies, syndactyly, cardiac defects, and a horseshoe kidney associated with terminal deletion of 2q. The infant`s karyotype was 46,XY,del(2)(q37). Clinical, cytogenetic, and autopsy findings are presented in this report. Clinical manifestations in this infant are compared with those four other known patients with terminal deletion of chromosome 2. 5 refs., 1 fig., 1 tab.

  20. Induction of cell proliferation, clonogenicity and cell accumulation in S phase as a consequence of human UBE2Q1 overexpression

    PubMed Central

    Fahmidehkar, Mohammad Ali; Shafiee, Sayed Mohammad; Eftekhar, Ebrahim; Mahbudi, Laleh; Seghatoleslam, Atefeh

    2016-01-01

    Ubiquitination is an important cellular mechanism with a pivotal role in the degradation of abnormal or short-lived proteins and the regulation of cell cycle and cell growth. The ubiquitin-proteasome pathway is altered in multiple types of human malignancies, including colorectal cancer (CRC). The alteration in the expression of the novel human gene ubiquitin-conjugating enzyme E2 Q1 (UBE2Q1), as a putative member of the E2 ubiquitin-conjugating enzyme family, has been reported in several malignancies, including carcinoma of the breast, hepatocellular and colorectal cancer, and pediatric acute lymphoblastic leukemia. In the present study, the effect of UBE2Q1 overexpression on cell growth, clonogenicity, motility and cell cycle was investigated in a CRC cell line. The UBE2Q1 gene was cloned in the pCMV6-AN-GFP expression vector. A series of stable transfectants of SW1116 cells overexpressing UBE2Q1 protein were established and confirmed by fluorescence microscopy and western blotting. Using these cells, MTT assay was performed to evaluate cell growth and proliferation, while crystal violet staining was used for clonogenicity assay. Cell cycle analysis was also performed to survey the ratio of cells accumulated in different phases of the cell cycle upon transfection. The motility of these cells was also studied using wound healing assay. UBE2Q1 transfectants exhibited a faster growth in cell culture, increased colony formation capacity and enhanced motility compared with control non-transfected cells and cells transfected with empty vector (mock-transfected cells). UBE2Q1 overexpression also resulted in a significant decrease in the number of cells accumulated in the G0/G1 phase of the cell cycle. The present findings suggest that UBE2Q1 may function as an oncogene that induces proliferation of cancer cells, and could be a novel diagnostic tool and a potential therapeutic target for CRC. PMID:27602158

  1. A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

    PubMed Central

    Di Gregorio, Eleonora; Calcia, Alessandro; Savin, Elisa

    2014-01-01

    A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely, KATNAL1, LINC00426, and HMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified a de novo microdeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development. PMID:25506442

  2. Normal phenotype with maternal isodisomy in a female with two isochromosomes: i(2p) and i(2q)

    SciTech Connect

    Bernasconi, F.; Dutly, F.; Schinzel, A.A.

    1996-11-01

    A 36-year-old normal healthy female was karyotyped because all of her five pregnancies had terminated in spontaneous abortions during the first 3 mo. Cytogenetic investigation disclosed a female karyotype with isochromosomes of 2p and 2q replacing the two normal chromosomes 2. Her husband and both of her parents had normal karyotypes. Molecular studies revealed maternal only inheritance for chromosome 2 markers. Reduction to homozygosity of all informative markers indicated that the isochromosomes derived from a single maternal chromosome 2. Except for the possibility of homozygosity for recessive mutations, maternal uniparental disomy 2 appears to have no adverse impact on the phenotype. Our data indicate that no maternally imprinted genes with major effect map to chromosome 2. 17 refs., 2 figs., 1 tab.

  3. Familial Klippel-Feil syndrome and paracentric inversion inv(8)(q22.2q23.3)

    SciTech Connect

    Clarke, R.A.; Kearsley, J.H.; Singh, S.

    1995-12-01

    Klippel-Feil syndrome (KFS) is characterized by congenital vertebral fusion believed to result from faulty segmentation along the embryo`s developing axis. KFS appears to be a heterogeneous disease often associated with craniofacial malformation. Here we provide the first evidence of a familial KFS gene locus on 8q, where an inv(8)(q22.2q23.3) has been found segregating with congenital vertebral fusion. The four-generation KF2-01 family present with a dominant form of the KFS where the sequence of vertebral fusion was confined to the cervical spine (always including the C2-3 fusion and reduced expression of the C4-5 and C6-7 fusions) in association with malformation of laryngeal cartilages and mild-to-severe vocal impairment. 32 refs., 4 figs., 1 tab.

  4. Normal phenotype with maternal isodisomy in a female with two isochromosomes: i(2p) and i(2q)

    PubMed Central

    Bernasconi, F.; Karagüzel, A.; Celep, F.; Keser, I.; Lüleci, G.; Dutly, F.; Schinzel, A. A.

    1996-01-01

    A 36-year-old normal healthy female was karyotyped because all of her five pregnancies had terminated in spontaneous abortions during the first 3 mo. Cytogenetic investigation disclosed a female karyotype with isochromosomes of 2p and 2q replacing the two normal chromosomes 2. Her husband and both of her parents had normal karyotypes. Molecular studies revealed maternal only inheritance for chromosome 2 markers. Reduction to homozygosity of all informative markers indicated that the isochromosomes derived from a single maternal chromosome 2. Except for the possibility of homozygosity for recessive mutations, maternal uniparental disomy 2 appears to have no adverse impact on the phenotype. Our data indicate that no maternally imprinted genes with major effect map to chromosome 2. Images Figure 1 Figure 2 PMID:8900241

  5. Congenital thrombocytopenia in a neonate with an interstitial microdeletion of 3q26.2q26.31.

    PubMed

    Bouman, Arjan; Knegt, Lia; Gröschel, Stefan; Erpelinck, Claudia; Sanders, Mathijs; Delwel, Ruud; Kuijpers, Taco; Cobben, Jan Maarten

    2016-02-01

    Interstitial deletions encompassing the 3q26.2 region are rare. Only one case-report was published this far describing a patient with an interstitial deletion of 3q26.2 (involving the MDS1-EVI1 complex (MECOM)) and congenital thrombocytopenia. In this report we describe a case of a neonate with congenital thrombocytopenia and a constitutional 4.52 Mb deletion of 3q26.2q26.31 including TERC and the first 2 exons of MECOM, involving MDS1 but not EVI1. The deletion was demonstrated by array-CGH on lymphocytes. Our report confirms that congenital thrombocytopenia can be due to a constitutional deletion of 3q26.2 involving MECOM. We suggest that in case of unexplained neonatal thrombocytopenia, with even just slight facial dysmorphism, DNA microarray on peripheral blood should be considered early in the diagnostic work-up.

  6. Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

    PubMed Central

    Labbé, Catherine; Ogaki, Kotaro; Lorenzo-Betancor, Oswaldo; Carrasquillo, Minerva M.; Heckman, Michael G.; McCarthy, Allan; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Dickson, Dennis W.; Uitti, Ryan J.; Wszolek, Zbigniew K.; Ross, Owen A.

    2015-01-01

    Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. PMID:26090850

  7. The Cannabinoid Receptor 2 Q63R Variant Modulates the Relationship between Childhood Obesity and Age at Menarche

    PubMed Central

    Torella, Marco; Miraglia del Giudice, Emanuele; Nobili, Bruno; Perrone, Laura; Maione, Sabatino; Rossi, Francesca

    2015-01-01

    Background The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement. Aim In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls. Methods We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay. Results In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1–3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years). Conclusion We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls. PMID:26447698

  8. Segregation of a familial balanced (12;10) insertion resulting in Dup(10)(q21.2q22.1) and Del(10)(q21.2q22.1) in first cousins.

    PubMed

    Doheny, K F; Rasmussen, S A; Rutberg, J; Semenza, G L; Stamberg, J; Schwartz, M; Batista, D A; Stetten, G; Thomas, G H

    1997-03-17

    An interchromosomal insertion in 3 generations of a family was ascertained through two developmentally delayed first cousins. Cytogenetic analysis using G-banding and chromosome painting showed an apparently balanced direct insertion of chromosome 10 material into chromosome 12, ins(12;10)(q15;q21.2q22.1), in the mothers and grandfather of these children. The proposita inherited only the derivative 10 chromosome, resulting in deletion of 10q21.2 --> 22.1 while her cousin inherited only the derivative 12, resulting in duplication of 10q21.2 --> 22.1. A comparison of the proposita with published deletion cases suggests a pattern of anomalies attributable to deletion of the 10q21 --> q22 region: developmental delay, hypotonia, a heart murmur, telecanthus, broad nasal root and ear abnormalities. This is the first report of a nontandem duplication of the 10q21 --> q22 region. The phenotype of the cousin with the duplication does not overlap greatly with published tandem 10q duplications. Finally, this report reaffirms the importance of obtaining family studies of patients with interstitial chromosomal abnormalities.

  9. Ordered-subsets linkage analysis detects novel Alzheimer disease loci on chromosomes 2q34 and 15q22.

    PubMed

    Scott, William K; Hauser, Elizabeth R; Schmechel, Donald E; Welsh-Bohmer, Kathleen A; Small, Gary W; Roses, Allen D; Saunders, Ann M; Gilbert, John R; Vance, Jeffery M; Haines, Jonathan L; Pericak-Vance, Margaret A

    2003-11-01

    Alzheimer disease (AD) is a complex disorder characterized by a wide range, within and between families, of ages at onset of symptoms. Consideration of age at onset as a covariate in genetic-linkage studies may reduce genetic heterogeneity and increase statistical power. Ordered-subsets analysis includes continuous covariates in linkage analysis by rank ordering families by a covariate and summing LOD scores to find a subset giving a significantly increased LOD score relative to the overall sample. We have analyzed data from 336 markers in 437 multiplex (>/=2 sampled individuals with AD) families included in a recent genomic screen for AD loci. To identify genetic heterogeneity by age at onset, families were ordered by increasing and decreasing mean and minimum ages at onset. Chromosomewide significance of increases in the LOD score in subsets relative to the overall sample was assessed by permutation. A statistically significant increase in the nonparametric multipoint LOD score was observed on chromosome 2q34, with a peak LOD score of 3.2 at D2S2944 (P=.008) in 31 families with a minimum age at onset between 50 and 60 years. The LOD score in the chromosome 9p region previously linked to AD increased to 4.6 at D9S741 (P=.01) in 334 families with minimum age at onset between 60 and 75 years. LOD scores were also significantly increased on chromosome 15q22: a peak LOD score of 2.8 (P=.0004) was detected at D15S1507 (60 cM) in 38 families with minimum age at onset >/=79 years, and a peak LOD score of 3.1 (P=.0006) was obtained at D15S153 (62 cM) in 43 families with mean age at onset >80 years. Thirty-one families were contained in both 15q22 subsets, indicating that these results are likely detecting the same locus. There is little overlap in these subsets, underscoring the utility of age at onset as a marker of genetic heterogeneity. These results indicate that linkage to chromosome 9p is strongest in late-onset AD and that regions on chromosome 2q34 and 15q22 are

  10. Holoprosencephaly with cerebellar vermis hypoplasia in 13q deletion syndrome: Critical region for cerebellar dysgenesis within 13q32.2q34.

    PubMed

    Mimaki, Masakazu; Shiihara, Takashi; Watanabe, Mio; Hirakata, Kyoko; Sakazume, Satoru; Ishiguro, Akio; Shimojima, Keiko; Yamamoto, Toshiyuki; Oka, Akira; Mizuguchi, Masashi

    2015-08-01

    We describe two unrelated patients with terminal deletions in the long arm of chromosome 13 showing brain malformation consisting of holoprosencephaly and cerebellar vermis hypoplasia. Array comparative genomic hybridization analysis revealed a pure terminal deletion of 13q31.3q34 in one patient and a mosaic ring chromosome with 13q32.2q34 deletion in the other. Mutations in ZIC2, located within region 13q32, cause holoprosencephaly, whereas the 13q32.2q32.3 region is associated with cerebellar vermis hypoplasia (Dandy-Walker syndrome). The rare concurrence of these major brain malformations in our patients provides further evidence that 13q32.2q32.3 deletion, harboring ZIC2 and ZIC5, leads to cerebellar dysgenesis.

  11. Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties.

    PubMed

    Peretz, Asher; Degani, Nurit; Nachman, Rachel; Uziyel, Yael; Gibor, Gilad; Shabat, Doron; Attali, Bernard

    2005-04-01

    The voltage-dependent M-type potassium current (M-current) plays a major role in controlling brain excitability by stabilizing the membrane potential and acting as a brake for neuronal firing. The KCNQ2/Q3 heteromeric channel complex was identified as the molecular correlate of the M-current. Furthermore, the KCNQ2 and KCNQ3 channel alpha subunits are mutated in families with benign familial neonatal convulsions, a neonatal form of epilepsy. Enhancement of KCNQ2/Q3 potassium currents may provide an important target for antiepileptic drug development. Here, we show that meclofenamic acid (meclofenamate) and diclofenac, two related molecules previously used as anti-inflammatory drugs, act as novel KCNQ2/Q3 channel openers. Extracellular application of meclofenamate (EC(50) = 25 microM) and diclofenac (EC(50) = 2.6 microM) resulted in the activation of KCNQ2/Q3 K(+) currents, heterologously expressed in Chinese hamster ovary cells. Both openers activated KCNQ2/Q3 channels by causing a hyperpolarizing shift of the voltage activation curve (-23 and -15 mV, respectively) and by markedly slowing the deactivation kinetics. The effects of the drugs were stronger on KCNQ2 than on KCNQ3 channel alpha subunits. In contrast, they did not enhance KCNQ1 K(+) currents. Both openers increased KCNQ2/Q3 current amplitude at physiologically relevant potentials and led to hyperpolarization of the resting membrane potential. In cultured cortical neurons, meclofenamate and diclofenac enhanced the M-current and reduced evoked and spontaneous action potentials, whereas in vivo diclofenac exhibited an anticonvulsant activity (ED(50) = 43 mg/kg). These compounds potentially constitute novel drug templates for the treatment of neuronal hyperexcitability including epilepsy, migraine, or neuropathic pain.

  12. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

    PubMed Central

    Ghoussaini, Maya; Edwards, Stacey L.

    2015-01-01

    GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the ‘iCOGS’ genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against > 100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER + ) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval = 0.84 – 0.87; P = 1.7 × 10 −43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology. PMID:25248036

  13. 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

    PubMed Central

    Li, Jingmei; Lindström, Linda S.; Foo, Jia N.; Rafiq, Sajjad; Schmidt, Marjanka K.; Pharoah, Paul D. P.; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Van ‘t Veer, Laura J.; Cornelissen, Sten; Rutgers, Emiel; Southey, Melissa C.; Apicella, Carmel; Dite, Gillian S.; Hopper, John L.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Blomqvist, Carl; Muranen, Taru A.; Aittomäki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa; Chenevix-Trench, Georgia; Investigators, kConFab; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe I. Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Hooning, Maartje; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Li, Yi; Hamann, Ute; Torres, Diana; Ulmer, Hans U.; Rüdiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Har Yip, Cheng; Fuang Ho, Gwo; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Maishman, Tom; Tapper, William J.; Dunning, Alison; Shah, Mitul; Luben, Robert; Brown, Judith; Chuen Khor, Chiea; Eccles, Diana M.; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila

    2014-01-01

    Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49–2.19); P for trend=1.90 × 10−9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities. PMID:24937182

  14. Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

    PubMed

    Ghoussaini, Maya; Edwards, Stacey L; Michailidou, Kyriaki; Nord, Silje; Cowper-Sal Lari, Richard; Desai, Kinjal; Kar, Siddhartha; Hillman, Kristine M; Kaufmann, Susanne; Glubb, Dylan M; Beesley, Jonathan; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Guo, Qi; Schmidt, Marjanka K; Shah, Mitul; Luben, Robert; Brown, Judith; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Klevebring, Daniel; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Lambrechts, Diether; Thienpont, Bernard; Neven, Patrick; Wildiers, Hans; Broeks, Annegien; Van't Veer, Laura J; Th Rutgers, Emiel J; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Peto, Julian; Dos-Santos-Silva, Isabel; Gibson, Lorna; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Qiuyin; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Lee, Daphne S C; Wong, Tien Y; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; van Deurzen, Carolien H M; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Kapuscinski, Miroslav K; Shen, Chen-Yang; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Alnæs, Grethe Grenaker; Borresen-Dale, Anne-Lise; Giles, Graham G; Milne, Roger L; McLean, Catriona; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Buhari, Shaik Ahmad Bin Syed; Teo, Yik Ying; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; García-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Brauch, Hiltrud; Brüning, Thomas; Koto, Yon-Dschun; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Dörk, Thilo; Bogdanova, Natalia V; Helbig, Sonja; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Hamann, Ute; Torres, Diana; Zheng, Wei; Long, Jirong; Anton-Culver, Hoda; Neuhausen, Susan L; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Alvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; de Santiago, Ines; Carroll, Jason; Caldas, Carlos; Brown, Melissa A; Lupien, Mathieu; Kristensen, Vessela N; Pharoah, Paul D P; Chenevix-Trench, Georgia; French, Juliet D; Easton, Douglas F; Dunning, Alison M

    2014-09-23

    GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.

  15. 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.

    PubMed

    Li, Jingmei; Lindström, Linda S; Foo, Jia N; Rafiq, Sajjad; Schmidt, Marjanka K; Pharoah, Paul D P; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Van 't Veer, Laura J; Cornelissen, Sten; Rutgers, Emiel; Southey, Melissa C; Apicella, Carmel; Dite, Gillian S; Hopper, John L; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Blomqvist, Carl; Muranen, Taru A; Aittomäki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M; Kataja, Vesa; Chenevix-Trench, Georgia; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe I Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Hooning, Maartje; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Li, Yi; Hamann, Ute; Torres, Diana; Ulmer, Hans U; Rüdiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Har Yip, Cheng; Fuang Ho, Gwo; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Maishman, Tom; Tapper, William J; Dunning, Alison; Shah, Mitul; Luben, Robert; Brown, Judith; Khor, Chiea Chuen; Eccles, Diana M; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila

    2014-06-17

    Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

  16. A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33-34.

    PubMed

    Thiffault, I; Rioux, M F; Tetreault, M; Jarry, J; Loiselle, L; Poirier, J; Gros-Louis, F; Mathieu, J; Vanasse, M; Rouleau, G A; Bouchard, J P; Lesage, J; Brais, B

    2006-09-01

    Recessive ataxias are a heterogeneous group of diseases. We identified a group of 23 French-Canadian cases belonging to 17 families affected by an autosomal recessive spastic ataxia associated with frequent white matter changes. The fact that 59% of these families have a genealogical relationship to the Portneuf County of Quebec suggests that this is a new form of ataxia with a regional founder effect. All cases present with cerebellar ataxia and spasticity. There is great intrafamilial and interfamilial variability, as illustrated by the spectrum of age of diagnosis (range: 2-59 years, mean: 15.0) and the presence of white matter changes on MRI in 52.4% of cases. The more severe cases have spasticity from birth, scoliosis, dystonia and cognitive impairment and were considered cases of cerebral palsy. Brain MRI constantly shows cerebellar atrophy, which in some cases may be associated with cortical atrophy, leucoencephalopathy and corpus callosum thinning. A genome wide scan uncovered linkage of three families to marker D2S2321 localized on chromosome 2q33-34. Linkage analysis confirmed that all families are linked to the same region [multipoint log of the odds (LOD) score of 5.95]. Haplotype analysis and allele sharing suggest that one common mutation may account for 97% of carrier chromosomes in Quebec. The uncovering of the mutated gene may point to a common pathway for pyramidal and cerebellar degeneration as both are often observed in recessive ataxias and complicated paraplegias.

  17. A Genome-Wide Association Study Identifies Susceptibility Loci for Ovarian Cancer at 2q31 and 8q24

    PubMed Central

    Goode, Ellen L.; Chenevix-Trench, Georgia; Song, Honglin; Ramus, Susan J.; Notaridou, Maria; Lawrenson, Kate; Widschwendter, Martin; Vierkant, Robert A.; Larson, Melissa C.; Kjaer, Susanne K.; Birrer, Michael J.; Berchuck, Andrew; Schildkraut, Joellen; Tomlinson, Ian; Kiemeney, Lambertus A.; Cook, Linda S.; Gronwald, Jacek; Garcia-Closas, Montserrat; Gore, Martin E.; Campbell, Ian; Whittemore, Alice S.; Sutphen, Rebecca; Phelan, Catherine; Anton-Culver, Hoda; Pearce, Celeste Leigh; Lambrechts, Diether; Rossing, Mary Anne; Chang-Claude, Jenny; Moysich, Kirsten B.; Goodman, Marc T.; Dörk, Thilo; Nevanlinna, Heli; Ness, Roberta B.; Rafnar, Thorunn; Hogdall, Claus; Hogdall, Estrid; Fridley, Brooke L.; Cunningham, Julie M.; Sieh, Weiva; McGuire, Valerie; Godwin, Andrew K.; Cramer, Daniel W.; Hernandez, Dena; Levine, Douglas; Lu, Karen; Iversen, Edwin S.; Palmieri, Rachel T.; Houlston, Richard; van Altena, Anne M.; Aben, Katja K.H.; Massuger, Leon F.A.G.; Brooks-Wilson, Angela; Kelemen, Linda E.; Le, Nhu D.; Jakubowska, Anna; Lubinski, Jan; Medrek, Krzysztof; Stafford, Anne; Easton, Douglas F.; Tyrer, Jonathan; Bolton, Kelly L.; Harrington, Patricia; Eccles, Diana; Chen, Ann; Molina, Ashley N.; Davila, Barbara N.; Arango, Hector; Tsai, Ya-Yu; Chen, Zhihua; Risch, Harvey A.; McLaughlin, John; Narod, Steven A.; Ziogas, Argyrios; Brewster, Wendy; Gentry-Maharaj, Aleksandra; Menon, Usha; Wu, Anna H.; Stram, Daniel O.; Pike, Malcolm C.; Beesley, Jonathan; Webb, Penelope M.; Chen, Xiaoqing; Ekici, Arif B.; Thiel, Falk C.; Beckmann, Matthias W.; Yang, Hannah; Wentzensen, Nicolas; Lissowska, Jolanta; Fasching, Peter A.; Despierre, Evelyn; Amant, Frederic; Vergote, Ignace; Doherty, Jennifer; Hein, Rebecca; Wang-Gohrke, Shan; Lurie, Galina; Carney, Michael E.; Thompson, Pamela J.; Runnebaum, Ingo; Hillemanns, Peter; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Butzow, Ralf; Heikkinen, Tuomas; Stefansson, Kari; Sulem, Patrick; Besenbacher, Sören; Sellers, Thomas A.; Gayther, Simon A.; Pharoah, Paul D.P.

    2011-01-01

    Ovarian cancer (OC) accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance OC susceptibility genes, we conducted a genome-wide association study (GWAS) of 507,094 SNPs in 1,768 cases and 2,354 controls, with follow-up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (BNC2)1. Here, we report on nine additional candidate loci (p≤10-4), identified after stratifying cases by histology, genotyped in an additional 4,353 cases and 6,021 controls. Two novel susceptibility loci with p≤5×10-8 were confirmed (8q24, p=8.0×10-15 and 2q31, p=3.8×10-14); two additional loci were also identified that approached genome-wide significance (3q25, p=7.1×10-8 and 17q21, p=1.4×10-7). The associations with serous OC were generally stronger than other subtypes. Analysis of HOXD1, MYC, TiPARP, and SKAP1 at these loci, and BNC2 at 9p22, supports a functional role for these genes in OC development. PMID:20852632

  18. Recognition of the Major Histocompatibility Complex (MHC) Class Ib Molecule H2-Q10 by the Natural Killer Cell Receptor Ly49C.

    PubMed

    Sullivan, Lucy C; Berry, Richard; Sosnin, Natasha; Widjaja, Jacqueline M L; Deuss, Felix A; Balaji, Gautham R; LaGruta, Nicole L; Mirams, Michiko; Trapani, Joseph A; Rossjohn, Jamie; Brooks, Andrew G; Andrews, Daniel M

    2016-09-02

    Murine natural killer (NK) cells are regulated by the interaction of Ly49 receptors with major histocompatibility complex class I molecules (MHC-I). Although the ligands for inhibitory Ly49 were considered to be restricted to classical MHC (MHC-Ia), we have shown that the non-classical MHC molecule (MHC-Ib) H2-M3 was a ligand for the inhibitory Ly49A. Here we establish that another MHC-Ib, H2-Q10, is a bona fide ligand for the inhibitory Ly49C receptor. H2-Q10 bound to Ly49C with a marginally lower affinity (∼5 μm) than that observed between Ly49C and MHC-Ia (H-2K(b)/H-2D(d), both ∼1 μm), and this recognition could be prevented by cis interactions with H-2K in situ To understand the molecular details underpinning Ly49·MHC-Ib recognition, we determined the crystal structures of H2-Q10 and Ly49C bound H2-Q10. Unliganded H2-Q10 adopted a classical MHC-I fold and possessed a peptide-binding groove that exhibited features similar to those found in MHC-Ia, explaining the diverse peptide binding repertoire of H2-Q10. Ly49C bound to H2-Q10 underneath the peptide binding platform to a region that encompassed residues from the α1, α2, and α3 domains, as well as the associated β2-microglobulin subunit. This docking mode was conserved with that previously observed for Ly49C·H-2K(b) Indeed, structure-guided mutation of Ly49C indicated that Ly49C·H2-Q10 and Ly49C·H-2K(b) possess similar energetic footprints focused around residues located within the Ly49C β4-stand and L5 loop, which contact the underside of the peptide-binding platform floor. Our data provide a structural basis for Ly49·MHC-Ib recognition and demonstrate that MHC-Ib represent an extended family of ligands for Ly49 molecules.

  19. Interstitial deletion of chromosome 2q32-34 associated with multiple congenital anomalies and a urea cycle defect (CPS I deficiency).

    PubMed

    Loscalzo, M L; Galczynski, R L; Hamosh, A; Summar, M; Chinsky, J M; Thomas, G H

    2004-07-30

    A de novo deletion of the long arm of chromosome 2 at 2q31-33 was observed in the fetal amniocyte G-banded karyotype performed because of possible multiple malformations identified by ultrasound at 23 weeks gestation. Two days after the uneventful term delivery of a 2.45 kg male, the neonate experienced cardiopulmonary decompensation and biochemical changes compatible with carbamoyl phosphate synthetase I (CPS I) deficiency (elevated ammonia with a peak of 948 micromol/L, deficiency of citrulline, and no increase in orotic acid). The child died on day 3 of life. Physical anomalies confirmed at autopsy included double superior vena cava, ectopic adrenal tissue, and metatarsus adductus. The autopsy also revealed histologic evidence consistent with CPS deficiency, most notably microvesicular steatosis of the liver and Alzheimer's Type II changes with hypertrophic astrocytes in the basal ganglia. A postnatal lymphocyte karyotype confirmed the chromosome 2q31-33 deletion. Enzyme analysis on postmortem liver tissue confirmed the diagnosis of CPS deficiency. CPS I is reported to be mapped to 2q35 by NCBI (http://www.ncbi.nlm.nih.gov/mapview/) and 2q34 by ENSEMBL (http://www.ensembl.org/). The UCSC Human Genome Browser July 2003 assembly also places the gene at 2q34 (http://genome.UCSC.edu/). Fluorescence in situ hybridization (FISH) analysis with a BAC clone (RP11-349G4) of CPS I demonstrated that one copy of the gene was deleted in this infant. Using additional probes corresponding to the bands in the region of deletion, we identified the deleted region as 2q32-2q34. Our observations support the CPS I map position (ENSEMBL, UCSC) at 2q34. Additionally, potential conditions associated with deletions narrowly defined by standard cytogenetic techniques merit consideration in prenatal counseling. As demonstrated here, deletions may not only result in malformations and mental retardation but also increase the likelihood of revealing mutated genes located in the undeleted

  20. Assignment of the gastric inhibitory polypeptide receptor gene (GIPR) to chromosome bands 19q13.2-q13.3 by fluorescence in situ hybridization

    SciTech Connect

    Stoffel, M.; Fernald, A.A.; Bell, G.I.; Le Beau, M.M.

    1995-08-10

    The gastric inhibitory polypeptide receptor gene (GIPR) was localized, using fluorescence in situ hybridization (FISH), to human chromosome bands 19q13.2-q13.3. Gastric inhibitory polypeptide (GIP) is a potent stimulator of insulin secretion and mutations in the GIPR gene may be related to non-insulin-dependent diabetes mellitus (NIDDM). 13 refs., 1 fig.

  1. A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil.

    PubMed

    Reis, F G; Pinto, I P; Minasi, L B; Melo, A V; Cunha, D M da C; Ribeiro, C L; da Silva, C C; Silva, D de M; da Cruz, A D

    2017-01-23

    Genomic disorders are genetic diseases that are caused by rearrangements of chromosomal material via deletions, duplications, and inversions of unique genomic segments at specific regions. Such rearrangements could result from recurrent non-allelic homologous recombination between low copy repeats. In cases where the breakpoints flank the low copy repeats, deletion of chromosomal segments is often followed by reciprocal duplication. Variations in genomic copy number manifest differently, with duplication and deletions of the same genomic region showing opposite phenotypes. Sotos syndrome is caused by alterations in the dosage of NSD1 on human chromosome 5 by either deletions or mutations, such as microdeletion of 5q35.2q35.3. In general, patients carrying reciprocal microduplication at 5q35.2q35.3 present no clinical phenotype or milder phenotype than do patients with microdeletion at the same locus. We report the first case of 5q35.2q35.3 microduplication encompassing NSD1 in a patient from central Brazil. We identified a genomic imbalance corresponding to a de novo 0.45 Mb microduplication at 5q35.2q35.3 by chromosomal microarray analysis and study of low-copy repeats. The proband had microduplication in the chromosomal region containing NSD1, which resulted in a Sotos syndrome reversed phenotype, and this duplication was associated with microcephaly, short stature, and developmental delay. Analysis of the genomic structure of the rearranged 5q35.2q35.3 chromosomal region revealed two major low-copy repeat families, which caused the recurrent rearrangements. Chromosomal microarray analysis is a potential tool to identify microrearrangements and guide medical diagnosis, which has to be followed by a non-directive genetic counseling approach to improve the quality of life of the patient.

  2. An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.

    PubMed

    Wyszynski, Asaf; Hong, Chi-Chen; Lam, Kristin; Michailidou, Kyriaki; Lytle, Christian; Yao, Song; Zhang, Yali; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Nordestgaard, Børge G; González-Neira, Anna; Benitez, Javier; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Wu, Anna H; Van Den Berg, David; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Dumont, Martine; Teo, Soo Hwang; Wong, Tien Y; Kristensen, Vessela; Zheng, Wei; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Figueroa, Jonine; Klevebring, Daniel; Czene, Kamila; Hooning, Maartje J; van den Ouweland, Ans M W; Darabi, Hatef; Shu, Xiao-Ou; Gao, Yu-Tang; Cox, Angela; Blot, William; Signorello, Lisa B; Shah, Mitul; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Miao, Hui; Hamann, Ute; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; McKay, James; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Wu, Pei-Ei; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Pharoah, Paul D P; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Bandera, Elisa; Amos, Chris; Ambrosone, Christine; Easton, Douglas F; Cole, Michael D

    2016-09-01

    Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 × 10(-19)) and identify 13 additional linked variants (r(2 )>( )0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 × 10(-15) - 5.6 × 10(-17)). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.

  3. Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality

    PubMed Central

    Kulminski, Alexander M.; He, Liang; Culminskaya, Irina; Loiko, Elena; Arbeeva, Liubov; Bagley, Olivia; Yashkin, Arseniy; Fang, Fang; Ukraintseva, Svetlana V.; Wu, Deqing; Yashin, Anatoliy I.

    2016-01-01

    Gaining insights into genetic predisposition to age-related diseases and lifespan is a challenging task complicated by the elusive role of evolution in these phenotypes. To gain more insights, we combined methods of genome-wide and candidate-gene studies. Genome-wide scan in the Atherosclerosis Risk in Communities (ARIC) Study (N = 9,573) was used to pre-select promising loci. Candidate-gene methods were used to comprehensively analyze associations of novel uncommon variants in Caucasians (minor allele frequency~2.5%) located in band 2q22.3 with risks of coronary heart disease (CHD), heart failure (HF), stroke, diabetes, cancer, neurodegenerative diseases (ND), and mortality in the ARIC study, the Framingham Heart Study (N = 4,434), and the Health and Retirement Study (N = 9,676). We leveraged the analyses of pleiotropy, age-related heterogeneity, and causal inferences. Meta-analysis of the results from these comprehensive analyses shows that the minor allele increases risks of death by about 50% (p = 4.6×10−9), CHD by 35% (p = 8.9×10−6), HF by 55% (p = 9.7×10−5), stroke by 25% (p = 4.0×10−2), and ND by 100% (p = 1.3×10−3). This allele also significantly influences each of two diseases, diabetes and cancer, in antagonistic fashion in different populations. Combined significance of the pleiotropic effects was p = 6.6×10−21. Causal mediation analyses show that endophenotypes explained only small fractions of these effects. This locus harbors an evolutionary conserved gene-desert region with non-coding intergenic sequences likely involved in regulation of protein-coding flanking genes ZEB2 and ACVR2A. This region is intensively studied for mutations causing severe developmental/genetic disorders. Our analyses indicate a promising target region for interventions aimed to reduce risks of many major human diseases and mortality. PMID:27832070

  4. Additional patient with del(12)(q21.2q22): further evidence for a candidate region for cardio-facio-cutaneous syndrome?

    PubMed

    Rauen, Katherine A; Albertson, Donna G; Pinkel, Daniel; Cotter, Philip D

    2002-06-01

    Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinct facial appearance, cardiac defects, ectodermal anomalies and developmental delay. Recently, we reported a 19-month-old girl with phenotypic manifestations consistent with the CFC syndrome who had an interstitial deletion of the long arm of chromosome 12, del(12)(q21.2q22), implicating a possible locus for CFC syndrome. Here, we report an additional patient with a cytogenetically identical interstitial deletion: 47,XYY,del(12)(q21.2q22). To further characterize this deletion we used microarray-based comparative genomic hybridization (array CGH). Array CGH confirmed both the deletion and the second Y chromosome. The deletion on chromosome 12q spanned at least 14 Mb as indicated by the positions on the genome sequence of the 4 BAC clones included in the deletion. While the proband did not have the classic features of CFC, he had some dysmorphic craniofacial characteristics, ectodermal anomalies and moderate developmental delay which were suggestive of CFC syndrome; however, this patient did not have classical CFC. The phenotypic differences between the two del(12)(q21.2q22) patients may be due to variability in the expression of the syndrome, or this deletion may present as a syndrome with overlapping features. Alternatively, the phenotypic differences may result from discordance at the molecular level, which may yield a critical minimal region of deletion for CFC. The region 12q21.2 --> q22 remains a possible candidate region for CFC syndrome. Additional characterization of these and other CFC patients may confirm and further refine this candidate region.

  5. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse.

    PubMed Central

    Foy, C; Newton, V; Wellesley, D; Harris, R; Read, A P

    1990-01-01

    We have demonstrated close linkage between the locus for the autosomal dominant Waardenburg syndrome type I and the placental alkaline phosphatase locus on chromosome 2q37. In five families the peak lod score was 4.76 at a recombination fraction of .023. In the mouse the Splotch locus maps to near the homologous position. Splotch mice have white spotting and hearing defects, suggesting that Splotch may be the murine homologue of Waardenburg syndrome type I. PMID:2339698

  6. Genetic and physical mapping of 2q35 in the region of NRAMP and IL8R genes: Identification of a polymorphic repeat in exon 2 of NRAMP

    SciTech Connect

    White, J.K.; Shaw, M.A.; Barton, C.H.

    1994-11-15

    Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the Il8RB gene in 35 pedigrees previously typed for markers in the 2q33-37 interval provided evidence (lod scores > 3) for linkage between Il8RB and the 2q34-135 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5{prime} LSH to 3{prime} VIL1 representing {approx}3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype. 38 refs., 4 figs., 3 tabs.

  7. Epilepsy phenotype associated with a chromosome 2q24.3 deletion involving SCN1A: Migrating partial seizures of infancy or atypical Dravet syndrome?

    PubMed

    Lim, Byung Chan; Hwang, Hee; Kim, Hunmin; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Yum, Mi-Sun; Ko, Tae-Sung

    2015-01-01

    The deletion of a sodium channel gene cluster located on chromosome 2q24.3 is associated with variable epilepsy phenotypes, including Dravet syndrome and migrating partial seizures of infancy. Although SCN1A is considered as the major contributor to the epilepsy phenotype, the role of other sodium channel genes that map within this cluster has not been delineated. We presented five new cases with a chromosome 2q24.3 deletion involving SCN1A and investigated their epilepsy phenotype in relation to the extent of the deletion. Three cases with deletion of the whole sodium channel gene cluster (SCN3A, SCN2A, SCN1A, SCN9A, and SCN7A) exhibited a complex epilepsy phenotype that was atypical for Dravet syndrome and suggestive of migrating partial seizures of infancy: early seizure onset (before 2 months of age), severe developmental delay from seizure onset, multifocal interictal spikes, polymorphous focal seizures, and acquired microcephaly. Two cases with partial deletion of SCN1A and SCN9A and whole SCN1A deletion had an epilepsy phenotype of Dravet syndrome. A literature review of cases with chromosome 2q24.3 deletion revealed that, in most Dravet syndrome cases, it does not involve SCN2A and SCN3A, whereas a complex epilepsy phenotype that is shared with migrating partial seizures of infancy was associated with cases of deletion of the whole sodium channel gene cluster.

  8. Somatic and germ-line mosaicism of deletion 15q11.2-q13 in a mother of dyzigotic twins with Angelman syndrome.

    PubMed

    Sánchez, Javier; Fernández, Raquel; Madruga, Marcos; Bernabeu-Wittel, José; Antiñolo, Guillermo; Borrego, Salud

    2014-02-01

    Angelman syndrome (AS, OMIM105830) is a neurogenetic disorder caused by different genetic mechanisms. Determining the genetic mechanism is essential to establish the recurrence risk and the accuracy of genetic/reproductive counseling. The majority of AS patients present with a deletion of the 15q11.2-q13 region on the maternally derived chromosome. The other genetic mechanisms are: paternal disomy of chromosome 15, imprinting center defects, and mutations in the ubiquitin-protein ligase E3A gene (UBE3A). Different recurrence risks are associated with each specific genetic mechanism involved. We report on the study of dizygotic twins with classic phenotypic AS due to deletion of the same maternally derived chromosome 15. The mother presented with hypopigmented macular lesions on the inner side of both arms. Fibroblast culture studies of the maternal hypopigmented skin areas from both arms showed mosaicism for a normal cell line and for a second cell line with a 15q11.2-q13 deletion. This family represents the first demonstrated case of maternal somatic and germ line mosaicism for 15q11.2-q13 deletion as the cause of AS.

  9. De Novo 17q24.2-q24.3 microdeletion presenting with generalized hypertrichosis terminalis, gingival fibromatous hyperplasia, and distinctive facial features.

    PubMed

    Afifi, Hanan H; Fukai, Ryoko; Miyake, Noriko; Gamal El Din, Amina A; Eid, Maha M; Eid, Ola M; Thomas, Manal M; El-Badry, Tarek H; Tosson, Angie M S; Abdel-Salam, Ghada M H; Matsumoto, Naomichi

    2015-10-01

    Generalized hypertrichosis is a feature of several genetic disorders, and the nosology of these entities is still provisional. Recent studies have implicated chromosome 17q24.2-q24.3 microdeletion and the reciprocal microduplication in a very rare form of congenital generalized hypertrichosis terminalis (CGHT) with or without gingival hyperplasia. Here, we report on a 5-year-old Egyptian girl born to consanguineous parents. The girl presented with CGHT and gingival hyperplasia for whom we performed detailed clinical, pathological, and molecular studies. The girl had coarse facies characterized by bilateral epicanthic folds, thick and abundant eyelashes, a broad nose, full cheeks, and lips that constituted the distinctive facial features for this syndrome. Biopsy of the gingiva showed epithelial marked acanthosis and hyperkeratosis with hyperplastic thick collagen bundles and dense fibrosis in the underlying tissues. Array analysis indicated a 17q24.2-q24.3 chromosomal microdeletion. We validated this microdeletion by real-time quantitative PCR and confirmed a perfect co-segregation of the disease phenotype within the family. In summary, this study indicates that 17q24.2-q24.3 microdeletion caused CGHT with gingival hyperplasia and distinctive facies, which should be differentiated from the autosomal recessive type that lacks the distinctive facies.

  10. Synthesis and electroluminescence characterization of a new aluminum complex, [8-hydroxyquinoline] bis [2, 2'bipyridine] aluminum Al(Bpy)2q

    NASA Astrophysics Data System (ADS)

    Rahul, Kumar; Ritu, Srivastava; Punita, Singh

    2016-01-01

    We have synthesized and characterized a new electroluminescent material, [8-hydroxyquinoline] bis [2,2'bipyridine] aluminum. A solution of this material Al(Bpy)2q in toluene showed absorption maxima at 380 nm, which was attributed to the moderate energy (π-π*) transitions of the aromatic rings. The photoluminescence spectrum of Al(Bpy)2q in the toluene solution showed a peak at 518 nm. This material shows thermal stability up to 300 °C. The structure of the device is ITO/F4-TCNQ (1 nm)/α-NPD (35 nm)/Al(Bpy)2q (35 nm)/ BCP (6 nm)/Alq3 (28 nm)/LiF (1 nm)/Al (150 nm). This device exhibited a luminescence peak at 515 nm (CIE coordinates, x = 0.32, y = 0.49). The maximum luminescence of the device was 214 cd/m2 at 21 V. The maximum current efficiency of OLED was 0.12 cd/A at 13 V and the maximum power efficiency was 0.03 lm/W at 10 V.

  11. Support for schizophrenia susceptibility locus on chromosome 2q detected in a Swedish isolate using a dense map of microsatellites and SNPs.

    PubMed

    Aberg, Karolina; Axelsson, Elin; Saetre, Peter; Jiang, Lin; Wetterberg, Lennart; Pettersson, Ulf; Lindholm, Eva; Jazin, Elena

    2008-10-05

    Extended pedigrees are not only very useful to identify disease genes for rare Mendelian conditions, but they may also help unravel the genetics of complex diseases such as schizophrenia. In this study we performed genome-wide multipoint non-parametric linkage (NPL) score calculations using 825 microsatellites and 5,366 single nucleotide polymorphisms (SNPs), respectively, and searched for haplotypes shared by affected individuals, in three multiplex families including 29 genotyped affected individuals which in total contains 49 relative pairs useful for linkage studies. The most consistent results for microsatellites and SNPs were observed on 2q12.3-q14.1 (NPL scores 2.0, empirical P-value 0.009). However, the overall highest NPL score was observed on chromosome 2q33.3 using SNPs (NPL score 2.2, empirical P-value 0.007). Other chromosomal regions were detected on 5q15-q22.1, with microsatellites (NPL scores 1.7, empirical P-value 0.021) and with SNPs (NPL scores 2.0, empirical P-value 0.010) and on 5q23.1 (NPL score 1.9, empirical P-value 0.012) and 8q24.1-q24.2 (NPL score 2.1, empirical P-value 0.009) when using SNPs. The analysis of extended pedigrees allowed the search for haplotypes inherited identical by decent (IBD) by affected individuals. In all regions with NPL score >1.9 we found haplotypes inherited IBD by multiple cases. However, no common haplotypes were found for affected individuals in all families. In conclusion our NPL results support earlier findings suggesting that 2q and possibly 5q and 8q contain susceptibility loci for schizophrenia. Haplotype sharing in families helped to delimit the detected regions that potentially are susceptibility loci for schizophrenia.

  12. Occurrence of nephroblastomatosis with dup(18)(q11.2-q23) implicates trisomy 18 tumor screening protocol in select patients with 18q duplication.

    PubMed

    Starr, Lois J; Sanmann, Jennifer N; Olney, Ann Haskins; Wandoloski, Melissa; Sanger, Warren G; Coulter, Donald W

    2014-04-01

    Duplications of the long arm of chromosome 18 have been previously reported in patients with phenotypic findings similar to full trisomy 18. Trisomy 18 increases the risk for Wilms tumor and it is currently recommended that these patients undergo abdominal ultrasonography screening every 6 months. We report on nephroblastomatosis in a 27-month-old male with a 55 Mb duplication of chromosome 18q11.2-q23 (chr18:22693370-77982126, hg 19) and propose that the trisomy 18 tumor screening protocol could also benefit patients with large 18q duplications.

  13. Blepharophimosis sequence (BPES) and microcephaly in a girl with del(3) (q22.2q23): a putative gene responsible for microcephaly close to the BPES gene?

    PubMed

    Ishikiriyama, S; Goto, M

    1993-09-15

    We report on a girl with the blepharophimosis sequence (BPES), microcephaly of postnatal onset, mild developmental retardation, and a deletion: 46,XX,del(3) (q22.2q23) de novo. A gene for BPES is suspected to be located at 3q23. Almost all cases with interstitial deletions containing 3q23 have not only BPES but also microcephaly and developmental retardation, while those without deletions, including those with apparently balanced translocations, only have BPES. Thus, a putative gene responsible for microcephaly may exist close to BPES gene. BPES, microcephaly, developmental retardation, and primary amenorrhea might constitute a contiguous gene syndrome.

  14. Unique de novo interstitial deletion of chromosome 17, del(17) (q23.2q24.3) in a female newborn with multiple congenital anomalies

    SciTech Connect

    Levin, M.L.; Shaffer, L.G.; Lewis, R.L.

    1995-01-02

    We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 (del(17) (q23.2q24.3)) who died on day of life 17 during a recurrent apneic episode. Her phenotype included severe growth retardation, multiple facial anomalies, maldeveloped oralpharyngeal structures, and digital and widespread skeletal anomalies. This patient`s phenotype was compared to two other reported patients with deletion 17q with minor clinical overlap consistent with a unique deletion. 9 refs., 2 figs.

  15. Solvothermal crystal growth of CuSbQ{sub 2} (Q=S, Se) and the correlation between macroscopic morphology and microscopic structure

    SciTech Connect

    Zhou Jian; Bian Guoqing; Zhu Qinyu; Zhang Yong; Li Chunying; Dai Jie

    2009-02-15

    A low temperature solvothermal method has been successfully used for preparation of two semiconductor compounds CuSbQ{sub 2} (Q=S(1), Se(2)) by the reactions of Cu, Sb and S(or Se) powders in 1,2-diaminopropane at 160 deg. C for 10 days. The crystal structure of 2 was determined first time using single crystal X-ray diffraction analyses. The structures of 1 and 2 are discussed in the view of covalent bonds and weak interactions. Double CuSbQ{sub 2} layers are assembled to a 3-D network structure by Cu...Sb and Q...Sb secondary bonds. In contrast with the isostructure of the two materials, the crystal morphology of them is quite different, brick-like crystals for CuSbS{sub 2} and plank-like crystals for CuSbSe{sub 2}. The phenomenon is related to their different inter-planar interactions. Semiconductor properties of the microcrystal samples are measured and the band gaps of 1 and 2 are 1.38 and 1.05 eV, respectively. - Graphical abstract: Two isostructural compounds, CuSbQ{sub 2} (Q=S, Se), display different morphologies in crystals, which is explained by comparing the strength of the interlayer interactions based on the crystal structure data.

  16. Co-occurrence of mosaic supernumerary isochromosome 18p and intermittent 2q13 deletions in a child with multiple congenital anomalies.

    PubMed

    Jaiswal, Sushil Kumar; Kumar, Ashok; Ali, Akhtar; Rai, Amit Kumar

    2015-03-15

    The present study deals with karyotpye-phenotype correlations in a six month old child with multiple congenital abnormalities. Cytogenetic analysis revealed mosaicism of a small metacentric supernumerary marker chromosome with a karyotype mos 47,XY+mar[34]/46,XY[31]. Cytogenetic microarray result showed three copies of chromosome 18p (15,400 kb in size). Moreover, 255 kbp intermittent deletion of chromosome 2q13 involving RGPD5, RGPD6, LIMS3, and LIMS3-LOC440895 was also observed. Correlating microarray data with the mosaic karyotype, the marker chromosome was identified as mosaic isochromosome 18p and was found to be 32,600 kbp in size. Baby resembled clinical characteristics of trisomy chromosome 18p, isochromosome 18p and trisomy chromosome 18. The present study suggested that deletion of evolutionarily conserved developmental genes (RGPD5, RGPD and LIMS3) in the 2q13 region might have contributed to more severity in phenotype as compared to so far such reported cases of 18p trisomy's, as these are involved in nuclear-cytoplasm trafficking, signaling for tissue patterning and differentiation.

  17. Characterization of Redox States of Ru(OH2)(Q)(tpy)2+ (Q = 3,5-di-tert-butyl-1,2-benzoquinone, tpy = 2,2#:6#,2#-terpyridine)and Related Species through Experimental and Theoretical Studies

    SciTech Connect

    Muckerman, J.T.; Tsai, M.-K.; , Rochford, J.; Polyansky, D.E.; Wada, T.; Tanaka, K.; Fujita, E.

    2009-04-27

    The redox states of Ru(OH{sub 2})(Q)(tpy){sup 2+} (Q = 3,5-di-tert-butyl-1,2-benzoquinone, tpy = 2,2':6',2''-terpyridine) are investigated through experimental and theoretical UV-vis spectra and Pourbaix diagrams. The electrochemical properties are reported for the species resulting from deprotonation and redox processes in aqueous solution. The formal oxidation states of the redox couples in the various intermediate complexes are systematically assigned using electronic structure theory. The controversy over the electronic assignment of ferromagnetic vs. antiferromagnetic coupling is investigated through comparison of ab initio methods and the broken-symmetry density functional theory (DFT) approach. The various pK{sub a} values and reduction potentials, including the consideration of proton-coupled electron-transfer (PCET) processes, are calculated, and the theoretical version of the Pourbaix diagram is constructed in order to elucidate and assign several previously ambiguous regions in the experimental diagram.

  18. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers.

    PubMed

    Antoniou, Antonis C; Sinilnikova, Olga M; McGuffog, Lesley; Healey, Sue; Nevanlinna, Heli; Heikkinen, Tuomas; Simard, Jacques; Spurdle, Amanda B; Beesley, Jonathan; Chen, Xiaoqing; Neuhausen, Susan L; Ding, Yuan C; Couch, Fergus J; Wang, Xianshu; Fredericksen, Zachary; Peterlongo, Paolo; Peissel, Bernard; Bonanni, Bernardo; Viel, Alessandra; Bernard, Loris; Radice, Paolo; Szabo, Csilla I; Foretova, Lenka; Zikan, Michal; Claes, Kathleen; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L; Ozcelik, Hilmi; Glendon, Gord; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Caligo, Maria A; Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Kaufman, Bella; Dagan, Efrat; Baruch, Ruth Gershoni; Friedman, Eitan; Harbst, Katja; Barbany-Bustinza, Gisela; Rantala, Johanna; Ehrencrona, Hans; Karlsson, Per; Domchek, Susan M; Nathanson, Katherine L; Osorio, Ana; Blanco, Ignacio; Lasa, Adriana; Benítez, Javier; Hamann, Ute; Hogervorst, Frans B L; Rookus, Matti A; Collee, J Margriet; Devilee, Peter; Ligtenberg, Marjolijn J; van der Luijt, Rob B; Aalfs, Cora M; Waisfisz, Quinten; Wijnen, Juul; van Roozendaal, Cornelis E P; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Evans, D Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Davidson, Rosemarie; Chu, Carol; Eccles, Diana; Cole, Trevor; Hodgson, Shirley; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Léoné, Mélanie; Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Caron, Olivier; Lenoir, Gilbert M; Sevenet, Nicolas; Longy, Michel; Ferrer, Sandra Fert; Prieur, Fabienne; Goldgar, David; Miron, Alexander; John, Esther M; Buys, Saundra S; Daly, Mary B; Hopper, John L; Terry, Mary Beth; Yassin, Yosuf; Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine; Hansen, Thomas v O; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo C; Wakeley, Katie; Boggess, John F; Basil, Jack; Schwartz, Peter E; Blank, Stephanie V; Toland, Amanda E; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny N; Allavena, Anna; Schmutzler, Rita K; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Niederacher, Dieter; Deissler, Helmut; Fiebig, Britta; Suttner, Christian; Schönbuchner, Ines; Gadzicki, Dorothea; Caldes, Trinidad; de la Hoya, Miguel; Pooley, Karen A; Easton, Douglas F; Chenevix-Trench, Georgia

    2009-11-15

    Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.

  19. Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism.

    PubMed

    Dennis, J; Truong, V; Aïssi, D; Medina-Rivera, A; Blankenberg, S; Germain, M; Lemire, M; Antounians, L; Civelek, M; Schnabel, R; Wells, P; Wilson, M D; Morange, P-E; Trégouët, D-A; Gagnon, F

    2016-10-01

    Essentials Tissue factor pathway inhibitor (TFPI) regulates the blood coagulation cascade. We replicated previously reported linkage of TFPI plasma levels to the chromosome 2q region. The putative causal locus, rs62187992, was associated with TFPI plasma levels and thrombosis. rs62187992 was marginally associated with TFPI expression in human aortic endothelial cells. Click to hear Ann Gil's presentation on new insights into thrombin activatable fibrinolysis inhibitor SUMMARY: Background Tissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial thromboembolism and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes. Objectives To replicate the finding of the linkage region in an independent sample, and to identify the causal locus. Methods We first performed a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study, and replicated the finding of the linkage peak on chromosome 2q (LOD = 3.06). We next defined a follow-up region that included 112 603 single nucleotide polymorphisms (SNPs) under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and the Marseille Thrombosis Association (MARTHA) Study, a study of 1033 unrelated VTE patients. SNPs with false discovery rate q-values of < 0.10 were tested for association with TFPI plasma levels in 892 patients with coronary artery disease in the AtheroGene Study. Results and Conclusions One SNP, rs62187992, was associated with TFPI plasma levels in all three samples (β = + 0.14 and P = 4.23 × 10(-6) combined; β = + 0.16 and P = 0.02 in the F5L Family Study; β = + 0.13 and P = 6.3 × 10(-4) in the MARTHA Study; β = + 0.17 and P = 0.03 in the AtheroGene Study), and contributed to the linkage peak in the F5L Family Study. rs

  20. 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

    PubMed

    Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

    2017-04-01

    Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

  1. Regional assignment of the human uroporphyrinogen III synthase (UROS) gene to chromosome 10q25.2----q26.3.

    PubMed

    Astrin, K H; Warner, C A; Yoo, H W; Goodfellow, P J; Tsai, S F; Desnick, R J

    1991-05-01

    Uroporphyrinogen III synthase [UROS; hydroxymethylbilane hydro-lyase (cyclizing), EC 4.2.1.75] is the fourth enzyme in the human heme biosynthetic pathway. The recent isolation of the cDNA encoding human UROS facilitated its chromosomal localization. Human UROS sequences were specifically amplified by the polymerase chain reaction (PCR) from genomic DNA of two independent panels of human-rodent somatic cell hybrids. There was 100% concordance for the presence of the human UROS PCR product and human chromosome 10. For each of the other chromosomes, there was 19%-53% discordance with human UROS. The chromosomal assignment was confirmed by Southern hybridization analysis of DNA from somatic cell hybrids with the full-length UROS cDNA. Using human-rodent hybrids containing different portions of human chromosome 10, we assigned the UROS gene to the region 10q25.2----q26.3.

  2. A new three-way variant t(15;22;17)(q22;q11.2;q21) in acute promyelocytic leukemia.

    PubMed

    Kato, Takayasu; Hangaishi, Akira; Ichikawa, Motoshi; Motokura, Toru; Takahashi, Tsuyoshi; Kurokawa, Mineo

    2009-03-01

    Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARA) at 17q21. We report the case of a 44-year-old man with APL carrying a new complex variant translocation (15;22;17). Karyotypic analysis with G-banding of bone marrow cells revealed t(15;22;17) (q22;q11.2;q21). Fluorescence in situ hybridization with a PML/RARA dual-color DNA probe showed the fusion signals. RT-PCR analysis showed long-form PML/RARA fusion transcripts. A complete remission was attained with a course of conventional chemotherapy with all-trans retinoic acid (ATRA). This is the first report of a new three-way translocation of 22q11 involvement with APL.

  3. Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration

    PubMed Central

    Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

    2008-01-01

    Background Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered. PMID:18405349

  4. An investigation of structural parameters and magnetic and optical properties of EuLn{sub 2}Q{sub 4} (Ln=Tb-Lu, Q=S, Se)

    SciTech Connect

    Jin Gengbang; Choi, Eun Sang; Guertin, Robert P.; Albrecht-Schmitt, Thomas E.

    2008-01-15

    EuLn{sub 2}Q{sub 4} (Ln=Tb-Lu; Q=S, Se) has been synthesized using Sb{sub 2}Q{sub 3} (Q=S, Se) fluxes at 1000 deg. C. These compounds crystallize in a CaFe{sub 2}O{sub 4}-type three-dimensional channel structure that is built from edge-shared double rutile chains of [LnQ{sub 6}] octahedra running down the b-axis. Each double chain is connected at the vertices to four other double chains to form open channels where bicapped trigonal prismatic Eu{sup 2+} ions reside. All of these compounds show antiferromagnetic ordering with Neel temperatures, T{sub N}{approx}3-4 K. The optical band gaps for EuTb{sub 2}Se{sub 4}, EuDy{sub 2}Se{sub 4}, EuHo{sub 2}Se{sub 4}, EuEr{sub 2}Se{sub 4}, EuTm{sub 2}Se{sub 4}, EuYb{sub 2}Se{sub 4} EuLu{sub 2}Se{sub 4}, and EuYb{sub 2}S{sub 4} are found to be 2.0, 1.8, 1.8, 1.7, 1.8, 1.3, 1.7, and 1.6 eV, respectively. - Graphical abstract: A view of the three-dimensional channel structure of EuYb{sub 2}S{sub 4} down the b-axis.

  5. Characterization of two ectrodactyly-associated translocation breakpoints separated by 2.5 Mb on chromosome 2q14.1-q14.2.

    PubMed

    David, Dezso; Marques, Bárbara; Ferreira, Cristina; Vieira, Paula; Corona-Rivera, Alfredo; Ferreira, José Carlos; van Bokhoven, Hans

    2009-08-01

    Split hand-split foot malformation or ectrodactyly is a heterogeneous congenital defect of digit formation. The aim of this study is the mapping of the breakpoints and a detailed molecular characterization of the candidate genes for an isolated and syndromic form of ectrodactyly, both associated with de novo apparently balanced chromosome translocations involving the same chromosome 2 band, [t(2;11)(q14.2;q14.2)] and [t(2;4)(q14.1;q35)], respectively. Breakpoints were mapped by fluorescence in situ hybridization using bacterial artificial chromosome clones. Where possible, these breakpoints were further delimited. Candidate genes were screened for pathogenic mutations and the expression levels of two of them analysed. The isolated bilateral split foot malformation-associated chromosome 2 breakpoint was localized at 120.9 Mb, between the two main candidate genes, encoding GLI-Kruppel family member GLI2 and inhibin-betaB. The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1. No clear pathogenic mutations were identified in any of these genes. The breakpoint between INHBB and GLI2 coincides with a previously identified translocation breakpoint associated with ectrodactyly. We propose a mechanism by which translocations in the 2q14.1-q14.2 region disrupt the specific arrangement of long-range regulatory elements that control the tight quantitative spatiotemporal expression of one or more genes from the breakpoint region.

  6. Copy-number mutations on chromosome 17q24.2-q24.3 in congenital generalized hypertrichosis terminalis with or without gingival hyperplasia.

    PubMed

    Sun, Miao; Li, Ning; Dong, Wu; Chen, Zugen; Liu, Qing; Xu, Yiming; He, Guang; Shi, Yongyong; Li, Xin; Hao, Jiajie; Luo, Yang; Shang, Dandan; Lv, Dan; Ma, Fen; Zhang, Dai; Hua, Rui; Lu, Chaoxia; Wen, Yaran; Cao, Lihua; Irvine, Alan D; McLean, W H Irwin; Dong, Qi; Wang, Ming-Rong; Yu, Jun; He, Lin; Lo, Wilson H Y; Zhang, Xue

    2009-06-01

    Congenital generalized hypertrichosis terminalis (CGHT) is a rare condition characterized by universal excessive growth of pigmented terminal hairs and often accompanied with gingival hyperplasia. In the present study, we describe three Han Chinese families with autosomal-dominant CGHT and a sporadic case with extreme CGHT and gingival hyperplasia. We first did a genome-wide linkage scan in a large four-generation family. Our parametric multipoint linkage analysis revealed a genetic locus for CGHT on chromosome 17q24.2-q24.3. Further two-point linkage and haplotyping with microsatellite markers from the same chromosome region confirmed the genetic mapping and showed in all the families a microdeletion within the critical region that was present in all affected individuals but not in unaffected family members. We then carried out copy-number analysis with the Affymetrix Genome-Wide Human SNP Array 6.0 and detected genomic microdeletions of different sizes and with different breakpoints in the three families. We validated these microdeletions by real-time quantitative PCR and confirmed their perfect cosegregation with the disease phenotype in the three families. In the sporadic case, however, we found a de novo microduplication. Two-color interphase FISH analysis demonstrated that the duplication was inverted. These copy-number variations (CNVs) shared a common genomic region in which CNV is not reported in the public database and was not detected in our 434 unrelated Han Chinese normal controls. Thus, pathogenic copy-number mutations on 17q24.2-q24.3 are responsible for CGHT with or without gingival hyperplasia. Our work identifies CGHT as a genomic disorder.

  7. Satb2 Haploinsufficiency Phenocopies 2q32-q33 Deletions, whereas Loss Suggests a Fundamental Role in the Coordination of Jaw Development

    PubMed Central

    Britanova, Olga; Depew, Michael J.; Schwark, Manuela; Thomas, Bethan L.; Miletich, Isabelle; Sharpe, Paul; Tarabykin, Victor

    2006-01-01

    The recent identification of SATB2 as a candidate gene responsible for the craniofacial dysmorphologies associated with deletions and translocations at 2q32-q33, one of only three regions of the genome for which haploinsufficiency has been significantly associated with isolated cleft palate, led us to investigate the in vivo functions of murine Satb2. We find that, similar to the way in which SATB2 is perceived to act in humans, craniofacial defects due to haploinsufficiency of Satb2, including cleft palate (in ∼25% of cases), phenocopy those seen with 2q32-q33 deletions and translocations in humans. Full functional loss of Satb2 results in amplification of these defects and leads both to increased apoptosis in the craniofacial mesenchyme where Satb2 is usually expressed and to changes in the pattern of expression of three genes implicated in the regulation of craniofacial development in humans and mice: Pax9, Alx4, and Msx1. The Satb2-dosage sensitivity in craniofacial development is conspicuous—along with its control of cell survival, pattern of expression, and reversible functional modification by SUMOylation, it suggests that Satb2/SATB2 function in craniofacial development may prove to be more profound than has been anticipated previously. Because jaw development is Satb2-dosage sensitive, the regulators of Satb2 expression and posttranslational modification become of critical importance both ontogenetically and evolutionarily, especially since such regulators plausibly play undetected roles in jaw and palate development and in the etiology of craniofacial malformations. PMID:16960803

  8. Linkage mapping of the gene for Type III collagen (COL3A1) to human chromosome 2q using a VNTR polymorphism

    SciTech Connect

    Tiller, G.E.; Polumbo, P.A.; Summar, M.L. )

    1994-03-15

    The gene for the [alpha]1(III) chain of type III collagen, COL3A1, has been previously mapped to human chromosome 2q24.3-q31 by in situ hybridization. Physical mapping by pulsed-field gel electrophoresis has demonstrated that COL3A1 lies within 35 kb of COL5A2. The authors genotyped the CEPH families at the COL3A2 locus using a pentanucleotide repeat polymorphism within intron 25. They demonstrated significant linkage to 18 anonymous markers as well as the gene for carbamyl phosphate synthetase (CPSI), which had been previously mapped to this region. No recombination was seen between COL3A1 and COL5A2 (Z = 9.93 at [theta] = 0) or D2S24 (Z = 10.55 at [theta] = 0). The locus order is (D2S32-D2S138-D2S148)-(D2S24-COL5A2-COL3A1)-(D2S118-D2S161), with odds of 1:2300 for the next most likely order. These relationships are consistent with the physical mapping of COL3A1 to the distal portion of 2q and place it proximal to CPSI by means of multipoint analysis. These linkage relationships should prove useful in further studies of Ehlers-Danlos syndrome type IV and carbamyl phosphate synthetase I deficiency and provide an additional framework for localizing other genes in this region. 13 refs., 2 figs., 1 tab.

  9. A novel interstitial deletion of 2q22.3 q23.3 in a patient with dysmorphic features, epilepsy, aganglionosis, pure red cell aplasia, and skeletal malformations.

    PubMed

    Bravo-Oro, Antonio; Lurie, Iosif W; Elizondo-Cárdenas, Gabriela; Peña-Zepeda, Claudia; Salazar-Martínez, Abel; Correa-González, Cecilia; Castrillo, José Luis; Avila, Silvia; Esmer, Carmen

    2015-08-01

    Many chromosomal deletions encompassing the 2q23.1 region have been described ranging from small deletions of 38 kb up to >19 Mb. Most phenotypic features of the 2q23.1 deletion syndrome are due to a MBD5 gene loss independent of the size of the deletion. Here, we describe a male patient harboring a novel interstitial deletion encompassing the 2q22.3 q23.3 chromosomal region. Array-CGH revealed a 7.1 Mb deletion causing haploinsufficiency of several genes including MBD5, ACVR2, KIF5C, and EPC2. This patient presents with additional findings to those already described in individuals who have deletions of MBD5 including toes absence of halluces, pure red cell aplasia, and intestinal aganglionosis. Interestingly, in the deleted region there are previously identified regulatory sequences which are located upstream to ZEB2, which is associated with Hirschsprung disease (HSCR). Several genes have been associated with pure red cell aplasia, but to our knowledge, this is the first time that 2q deletion is associated with this phenotype. These additional findings should be added to the list of manifestations associated with 2q deletion, and provide support for the hypothesis that this individual has a true contiguous gene deletion syndrome.

  10. Molecular cytogenetic characterization of a 2q35-q37 duplication and a 4q35.1-q35.2 deletion in two cousins: a genotype-phenotype analysis.

    PubMed

    Ronzoni, Luisa; Peron, Angela; Bianchi, Vera; Baccarin, Marco; Guerneri, Silvana; Silipigni, Rosamaria; Lalatta, Faustina; Bedeschi, Maria Francesca

    2015-07-01

    The 2q3 duplication and 4q3 deletion are two distinct conditions with variable phenotypes including developmental delay, intellectual disability, Pierre Robin sequence (PRS), and cardiovascular, craniofacial, digital and skeletal anomalies. We describe two cousins, a 37-year-old man (Patient 1) and a 17-year-old girl (Patient 2), with a derivative chromosome leading to a 4q35 deletion-2q35q37 duplication. Conventional karyotype showed in both patients the same rearrangement derived from unbalanced segregation of a parental reciprocal translocation involving the long arms of chromosome 2 and 4. Patient 1's father and Patient 2's mother were identified as the carriers of a balanced translocation t(2;4)(q35;q35). Array-CGH analysis, performed to characterize the rearrangement, documented in both patients the presence of a 26 Mb duplication of the 2q35-q37.3 region of chromosome 2 and a 6.3 Mb deletion of the 4q35.1-q35.2 region of chromosome 4. Both patients showed intellectual disability, minor facial, and digital anomalies, hearing, ocular, and genitourinary abnormalities. The comparison of their features with those of published cases of 2q3 duplication and 4q3 deletion allowed us to further delineate the genotype-phenotype correlation as well as the combined effect of partial 2q duplication and 4q deletion syndromes in adulthood.

  11. Mapping of a gene for alopecia with mental retardation syndrome (APMR3) on chromosome 18q11.2-q12.2.

    PubMed

    Wali, A; Ali, G; John, P; Lee, K; Chishti, M S; Leal, S M; Ahmad, W

    2007-09-01

    Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder characterized by total or partial absence of hair from the scalp and other parts of the body and associated with mental retardation. Previously, we have reported the mapping of two alopecia and mental retardation genes (APMR1 and APMR2) on human chromosome 3. In the present study, after excluding both of these loci through linkage analysis, a whole genome scan was performed by genotyping 396 polymorphic microsatellite markers located on 22 autosomes and the X and Y chromosomes. A disease locus was mapped to a 10.9 cM region, flanked by markers D18S866 and D18S811, on chromosome 18q11.2-q12.2. A maximum two-point LOD score of 3.03 at theta= 0.0 was obtained with marker D18S1102. Multipoint linkage analysis resulted in maximum LOD scores of 4.03 with several markers in the candidate region. According to the Rutgers combined linkage-physical map of the human genome (build 36) this region covers 12.17 Mb. DNA sequence analysis of nine candidate genes including DSC3, DSC1, DSG1, DSG4, DSG3, ZNF397, ZNF271, ZNF24 and ZNF396 did not reveal any sequence variants in the affected individuals of the family presented here.

  12. A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31.

    PubMed

    Wali, A; John, P; Gul, A; Lee, K; Chishti, M S; Ali, G; Hassan, M J; Leal, S M; Ahmad, W

    2006-09-01

    Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2.

  13. Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haploinsufficient genes influencing behavior and fat deposition.

    PubMed

    Migdalska, Anna M; van der Weyden, Louise; Ismail, Ozama; White, Jacqueline K; Sánchez-Andrade, Gabriela; Logan, Darren W; Arends, Mark J; Adams, David J

    2012-01-01

    Haploinsufficiency of part of human chromosome 21 results in a rare condition known as Monosomy 21. This disease displays a variety of clinical phenotypes, including intellectual disability, craniofacial dysmorphology, skeletal and cardiac abnormalities, and respiratory complications. To search for dosage-sensitive genes involved in this disorder, we used chromosome engineering to generate a mouse model carrying a deletion of the Lipi-Usp25 interval, syntenic with 21q11.2-q21.1 in humans. Haploinsufficiency for the 6 genes in this interval resulted in no gross morphological defects and behavioral analysis performed using an open field test, a test of anxiety, and tests for social interaction were normal in monosomic mice. Monosomic mice did, however, display impaired memory retention compared to control animals. Moreover, when fed a high-fat diet (HFD) monosomic mice exhibited a significant increase in fat mass/fat percentage estimate compared with controls, severe fatty changes in their livers, and thickened subcutaneous fat. Thus, genes within the Lipi-Usp25 interval may participate in memory retention and in the regulation of fat deposition.

  14. A cluster of ten novel MHC class I related genes on human chromosome 6q24.2-q25.3.

    PubMed

    Radosavljevic, Mirjana; Cuillerier, Benoît; Wilson, Michael J; Clément, Oliver; Wicker, Sophie; Gilfillan, Susan; Beck, Stephan; Trowsdale, John; Bahram, Seiamak

    2002-01-01

    We have identified a novel family of human major histocompatibility complex (MHC) class I genes. This MHC class I related gene family is defined by 10 members, among which 6 encode potentially functional glycoproteins. The 180-kb cluster containing them has been generated by serial duplication and minimal diversification of an ancestral prototype. They are not located within the MHC on 6p21.3, but near the tip of its long arm at q24.2-q25.3, close to the human equivalent of the mouse H2-linked t-complex, a subchromosomal region syntenic to a segment of mouse chromosome 10 harboring the orthologous MHC class I related retinoic acid early transcript loci, Raet1a-d. Hence we have named the identified loci RAET1E-N. Human RAET1 products are all devoid of the membrane-proximal immunoglobulin-like alpha3 domain and most, but not all, are predicted to remain membrane-anchored via glycosylphosphatidylinositol linkage and are shown to display an atypical pattern of polymorphism. RAET1 transcripts are absent from hematopoietic tissues, but largely expressed in tumors. The involvement of orthologous mouse RAET1A-D/H60 in natural killer and T-cell activation through NKG2D engagement augurs a similar function for the human RAET1 proteins.

  15. Differences Between the Pattern of Developmental Abnormalities in Autism Associated with Duplications 15q11.2-q13 and Idiopathic Autism

    PubMed Central

    Wegiel, Jerzy; Schanen, N. Carolyn; Cook, Edwin H.; Sigman, Marian; Brown, W. Ted; Kuchna, Izabela; Nowicki, Krzysztof; Wegiel, Jarek; Imaki, Humi; Ma, Shuang Yong; Marchi, Elaine; Wierzba-Bobrowicz, Teresa; Chauhan, Abha; Chauhan, Ved; Cohen, Ira L.; London, Eric; Flory, Michael; Lach, Boleslaw; Wisniewski, Thomas

    2013-01-01

    The purpose of this study was to identify differences in patterns of developmental abnormalities between the brains of individuals with autism of unknown etiology and those of individuals with duplications of chromosome 15q11.2-q13 [dup(15)] and autism, and to identify alterations that may contribute to seizures and sudden death in the latter. Brains of 9 subjects with dup(15), 10 with idiopathic autism, and 7 controls were examined. In the dup(15) cohort, 7 subjects (78%) had autism, 7 (78%) had seizures, and 6 (67%) had experienced sudden unexplained death. Subjects with dup(15) autism were microcephalic, with mean brain weights 300 g less (1,177 g) than those of subjects with idiopathic autism (1,477 g; p < 0.001). Heterotopias in the alveus, CA4, and dentate gyrus and dysplasia in the dentate gyrus were detected in 89% of dup(15) autism cases but in only 10% idiopathic autism cases (p < 0.001). By contrast, cerebral cortex dysplasia was detected in 50% of subjects with idiopathic autism and in no dup(15) autism cases (p < 0.04). The different spectrum and higher prevalence of developmental neuropathological findings in the dup(15) cohort than in cases with idiopathic autism may contribute to the high risk of early onset of seizures and sudden death. PMID:22487857

  16. Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease.

    PubMed

    Orlando, Giulia; Law, Philip J; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Aaltonen, Lauri A; Houlston, Richard S

    2016-06-01

    To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10(-8), odds ratio = 1.10, 95% confidence interval = 1.06-1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r(2) = 0.90, D' = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD.

  17. 1q25.2-q31.3 Deletion in a female with mental retardation, clinodactyly, minor facial anomalies but no growth retardation

    PubMed Central

    2013-01-01

    The reports of 1q25-32 deletion cases are rare. We reported here an 11-year-old Chinese Han female with an interstitial 1q25 deletion displaying mental retardation, clinodactyly of the 5th finger and minor facial anomalies. Notably, the patient did not present growth retardation which is quite common in patients with 1q25-32 deletion encompassing LHX4. The heterozygous deletion in this patient was characterized as 46,XX,del(1)(q25.2-q31.3) with a length of 20.5 Mb according to SNP-array test results. STRP (Short Tandem Repeat Polymorphism) analysis of the family trio indicated the genomic abnormality was de novo with paternal origin. After a genotype-phenotype analysis, we proposed here the loss of a 3.1 Mb critical region including 24 genes within 1q25.2 (chr1:174.5-177.6 Mb, build 36) may account for the mental retardation in patients with 1q25-32 deletion. PMID:23915434

  18. Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal gynecomastia: Clinical, chromosomal and aCGH characterization.

    PubMed

    Linhares, Natália D; Valadares, Eugênia R; da Costa, Silvia S; Arantes, Rodrigo R; de Oliveira, Luiz Roberto; Rosenberg, Carla; Vianna-Morgante, Angela M; Svartman, Marta

    2016-09-01

    We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.

  19. Variation at 2q35 (PNKD and TMBIM1) influences colorectal cancer risk and identifies a pleiotropic effect with inflammatory bowel disease

    PubMed Central

    Orlando, Giulia; Law, Philip J.; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A.; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N.; Meyer, Brian F.; Wakil, Salma M.; Campbell, Harry; Smith, Christopher G.; Idziaszczyk, Shelley; Maughan, Timothy S.; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D.; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Taipale, Jussi; Cheadle, Jeremy P.; Dunlop, Malcolm G.; Tomlinson, Ian P.; Aaltonen, Lauri A.; Houlston, Richard S.

    2016-01-01

    To identify new risk loci for colorectal cancer (CRC), we conducted a meta-analysis of seven genome-wide association studies (GWAS) with independent replication, totalling 13 656 CRC cases and 21 667 controls of European ancestry. The combined analysis identified a new risk association for CRC at 2q35 marked by rs992157 (P = 3.15 × 10−8, odds ratio = 1.10, 95% confidence interval = 1.06–1.13), which is intronic to PNKD (paroxysmal non-kinesigenic dyskinesia) and TMBIM1 (transmembrane BAX inhibitor motif containing 1). Intriguingly this susceptibility single-nucleotide polymorphism (SNP) is in strong linkage disequilibrium (r2 = 0.90, D′ = 0.96) with the previously discovered GWAS SNP rs2382817 for inflammatory bowel disease (IBD). Following on from this observation we examined for pleiotropy, or shared genetic susceptibility, between CRC and the 200 established IBD risk loci, identifying an additional 11 significant associations (false discovery rate [FDR]) < 0.05). Our findings provide further insight into the biological basis of inherited genetic susceptibility to CRC, and identify risk factors that may influence the development of both CRC and IBD. PMID:27005424

  20. Line mixing effects in solar occultation spectra of the lower stratosphere: measurements and comparisons with calculations for the 1932-cm(-1) CO(2) Q branch.

    PubMed

    Rinsland, C P; Strow, L L

    1989-02-01

    Line mixing effects have been observed in a CO(2)Q branch recorded in 0.01-cm(-1) resolution IR solar occultation spectra of the lower stratosphere. The spectral data were obtained by the Atmospheric Trace Molecule Spectroscopy Fourier transform spectrometer during the Spacelab 3 shuttle mission in the spring of 1985. Analysis of the 1932.47-cm(-1) (11102)?(00001) band Q branch of (12)C(16)O(2) shows absorption coefficients below the band origin approximately 0.62 times those calculated using a standard Voigt line shape function. Calculations of line mixing using the Lorentz halfwidths of the lines and a simple energy gap scaling law to parametrize rotational energy transfer reproduce the observed absorption coefficients to ~10%. The present results provide the first quantitative information on air-broadened line mixing effects in a Q branch at low temperatures (~210 K) and show that these effects are significant even at the low pressures of the lower stratosphere (~100 mbar).

  1. A Rare Inherited 15q11.2-q13.1 Interstitial Duplication with Maternal Somatic Mosaicism, Renal Carcinoma, and Autism

    PubMed Central

    Urraca, Nora; Potter, Brian; Hundley, Rachel; Pivnick, Eniko K.; McVicar, Kathryn; Thibert, Ronald L.; Ledbetter, Christopher; Chamberlain, Reed; Miravalle, Leticia; Sirois, Carissa L.; Chamberlain, Stormy; Reiter, Lawrence T.

    2016-01-01

    Chromosome 15q11-q13.1 duplication is a common copy number variant associated with autism spectrum disorder (ASD). Most cases are de novo, maternal in origin and fully penetrant for ASD. Here, we describe a unique family with an interstitial 15q11.2-q13.1 maternal duplication and the presence of somatic mosaicism in the mother. She is typically functioning, but formal autism testing showed mild ASD. She had several congenital anomalies, and she is the first 15q Duplication case reported in the literature to develop unilateral renal carcinoma. Her two affected children share some of these clinical characteristics, and have severe ASD. Several tissues in the mother, including blood, skin, a kidney tumor, and normal kidney margin tissues were studied for the presence of the 15q11-q13.1 duplication. We show the mother has somatic mosaicism for the duplication in several tissues to varying degrees. A growth competition assay in two types of stem cells from duplication 15q individuals was also performed. Our results suggest that the presence of this interstitial duplication 15q chromosome may confer a previously unknown growth advantage in this particular individual, but not in the general interstitial duplication 15q population. PMID:27933089

  2. Organization of the human gene for nucleobindin (NUC) and its chromosomal assignment to 19q13.2-q13.4

    SciTech Connect

    Miura, Keiji; Kurosawa, Yoshikazu; Hirai, Momoki

    1996-06-01

    Nucleobindin (Nuc) was first identified as a secreted protein of 55 kDa that promotes production of DNA-specific antibodies in lupus-prone MRL/lpr mice. Analysis of cDNA that encoded Nuc revealed that the protein is composed of a signal peptide, a DNA-binding site, two calcium-binding motifs (EF-hand motifs), and a leucine zipper. In the present study, we analysed the organization of the human gene for Nuc (NUC). It consists of 13 exons that are distributed in a region of 32 kb. The functional motifs listed above are encoded in corresponding exons. NUC was expressed in all organs examined. Comparison of nucleotide sequences in the promotre regions between human and mouse NCU genes revealed several conserved sequences. Among them, two Sp1-binding sites and a CCAAT box are of particular interest. The promoter is of the TATA-less type, and transcription starts at multiple sites in both the human and the mouse genes. These features suggest that NUC might normally play a role as a housekeeping gene. NUC was located at human chromosome 19q13.2-q13.4. 25 refs., 4 figs., 1 tab.

  3. Waardenburg syndrome (WS): the analysis of a single family with a WS1 mutation showing linkage to RFLP markers on human chromosome 2q.

    PubMed Central

    Asher, J H; Morell, R; Friedman, T B

    1991-01-01

    Waardenburg syndrome type I (WS1; MIM 19350) is caused by a pleiotropic, autosomal dominant mutation with variable penetrance and expressivity. Of individuals with this mutation, 20%-25% are hearing impaired. A multilocus linkage analysis of RFLP data from a single WS1 family with 11 affected individuals indicates that the WS1 mutation in this family is linked to the following four marker loci located on the long arm of chromosome 2: ALPP (alkaline phosphatase, placental), FN1 (fibronectin 1), D2S3 (a unique-copy DNA segment), and COL6A3 (collagen VI, alpha 3). For the RFLP marker loci, a multilocus linkage analysis using MLINK produced a peak lod (Z) of 3.23 for the following linkage relationships and recombination fractions (theta i): (ALPP----.000----FN1)----.122----D2S3----.267----CO L6A3. A similar analysis produced a Z of 6.67 for the following linkage relationships and theta i values among the markers and WS1: (FN1----.000----WS1----.000----ALPP)----.123----D2S 3----.246----COL6A3. The data confirm the conclusion of Foy et al. that at least some WS1 mutations map to chromosome 2q. Images Figure 2 PMID:1670751

  4. A unique de novo interstitial deletion of chromosome 17, del(17)(q23.2q24.3) in a female newborn with multiple congenital anomalies

    SciTech Connect

    Levin, M.L.; Shaffer, L.G.; Lewis, R.A.

    1994-09-01

    Contiguous gene or microdeletion syndromes occurring on chromosome 17p include the Smith-Magenis and Miller-Dieker syndromes associated with interstitial deletions of 17p11.2 and 17p13.3, respectively. Other cytogenetically visible interstitial deletions on chromosome 17 are quite rare or unique. We describe a newborn with a novel interstitial deletion of the long arm of chromosome 17 [del(17)(q23.2q24.3)] who died on day of life 17 during a recurrent apneic episode. We have compared our patient`s phenotype and karyotype to two reported patients with deletion 17q with minor clinical overlap. The most striking clinical features of this patient were severe intrauterine growth retardation, widespread skeletal malformations (split sutures, hypoplastic acetabulae and scapulae, vertebral anomalies, and digital hypoplasia), cutis verticis gyrata, dysmorphic facial features, and oropharyngeal malformations (absent uvula and submucous cleft palate). Mild congenital heart disease and anomalous optic nerves were also present. Parental karyotyps were normal. DNA from parents and patient has been collected and cell lines established on both parents. Genes which have been previously mapped to the region that is apparently deleted in this patient include: chorionic somatomammotropin A, growth hormone (normal), acid alpha-glucosidase, apolipoprotein H, and the alpha peptide of type 4 voltage gated sodium channel. As in other clinical cytogenetic syndromes, further descriptions of patients with similar or overlapping rearrangements in this region will be necessary to delineate genotype/phenotype correlations for chromosome 17.

  5. 3.2 Mb microdeletion in chromosome 7 bands q22.2-q22.3 associated with overgrowth and delayed bone age.

    PubMed

    Uliana, Vera; Grosso, Salvatore; Cioni, Maddalena; Ariani, Francesca; Papa, Filomena T; Tamburello, Silvia; Rossi, Elisa; Katzaki, Eleni; Mucciolo, Mafalda; Marozza, Annabella; Pollazzon, Marzia; Mencarelli, Maria Antonietta; Mari, Francesca; Balestri, Paolo; Renieri, Alessandra

    2010-01-01

    We report a patient with mental retardation, epilepsy, overgrowth, delayed bone age, peculiar facial features, corpus callosum hypoplasia, enlarged cisterna magna and right cerebellar hypoplasia. Array-CGH analysis revealed the presence of a de novo 3.2 Mb interstitial deletion of the long arm of chromosome 7 involving bands q22.2-q22.3. The rearrangement includes 15 genes and encompasses a genomic region that represents a site of frequent loss of heterozygosity in myeloid malignancies. Four genes are implicated in the control of cell cycle: SRPK2, MLL5, RINT1 and LHFPL3. Haploinsufficiency of these genes might therefore be associated with overgrowth and could confer susceptibility to cancers or other tumours, so that attention to this possibility would be appropriate during regular medical review. In conclusion, array-CGH analysis should be performed in patients with overgrowth where the known causes have already been excluded, because some still unclassified overgrowth syndromes may be caused by subtle genomic imbalances.

  6. A Rare Inherited 15q11.2-q13.1 Interstitial Duplication with Maternal Somatic Mosaicism, Renal Carcinoma, and Autism.

    PubMed

    Urraca, Nora; Potter, Brian; Hundley, Rachel; Pivnick, Eniko K; McVicar, Kathryn; Thibert, Ronald L; Ledbetter, Christopher; Chamberlain, Reed; Miravalle, Leticia; Sirois, Carissa L; Chamberlain, Stormy; Reiter, Lawrence T

    2016-01-01

    Chromosome 15q11-q13.1 duplication is a common copy number variant associated with autism spectrum disorder (ASD). Most cases are de novo, maternal in origin and fully penetrant for ASD. Here, we describe a unique family with an interstitial 15q11.2-q13.1 maternal duplication and the presence of somatic mosaicism in the mother. She is typically functioning, but formal autism testing showed mild ASD. She had several congenital anomalies, and she is the first 15q Duplication case reported in the literature to develop unilateral renal carcinoma. Her two affected children share some of these clinical characteristics, and have severe ASD. Several tissues in the mother, including blood, skin, a kidney tumor, and normal kidney margin tissues were studied for the presence of the 15q11-q13.1 duplication. We show the mother has somatic mosaicism for the duplication in several tissues to varying degrees. A growth competition assay in two types of stem cells from duplication 15q individuals was also performed. Our results suggest that the presence of this interstitial duplication 15q chromosome may confer a previously unknown growth advantage in this particular individual, but not in the general interstitial duplication 15q population.

  7. Congenital, low penetrance lymphedema of lower limbs maps to chromosome 6q16.2-q22.1 in an inbred Pakistani family.

    PubMed

    Malik, Sajid; Grzeschik, Karl-Heinz

    2008-03-01

    Hereditary lymphedema is a rare, lymphatic disorder resulting in the chronic swelling of the extremities. It shows wide inter- and intra-familial clinical heterogeneity as well as variability in the age of onset. There are more than four genetically distinct lymphedema conditions known and mutations in three genes have been discovered in families with lymphedema. However, many other familial lymphedemas do not show linkage with the known loci, suggesting genetic heterogeneity. Here, we describe a large inbred Pakistani family with congenital, progressive lymphedema confined to the lower limbs, which fades away at 40-45 years of age. This condition segregates in an autosomal dominant fashion with reduced penetrance. The features are close to primary lymphedema I, Nonne-Milory type (MIM 153100). We exclude this condition for linkage to the known loci for lymphedema by employing highly polymorphic microsatellite markers from these intervals. Then, through a genome-wide linkage study we show that the malformation in our family maps to chromosome 6q16.2-q22.1. The highest pair-wise LOD score (Z(max) = 3.19) was obtained with microsatellite marker D6S1671, and a multipoint score of 3.75 was obtained at 108 cM. Haplotype analysis indicated that the critical interval in this family flanks between markers D6S1716 and D6S303. Mutation analysis in FOXO3, a likely candidate within this interval, did not show any pathogenic change in the affected family subjects. Our study provides an evidence of a second locus for lymphedema type I. The discovery of the underlying gene could be helpful for the understanding of this heterogeneous hereditary condition.

  8. Identity by descent fine mapping of familial adult myoclonus epilepsy (FAME) to 2p11.2-2q11.2.

    PubMed

    Henden, Lyndal; Freytag, Saskia; Afawi, Zaid; Baldassari, Sara; Berkovic, Samuel F; Bisulli, Francesca; Canafoglia, Laura; Casari, Giorgio; Crompton, Douglas Ewan; Depienne, Christel; Gecz, Jozef; Guerrini, Renzo; Helbig, Ingo; Hirsch, Edouard; Keren, Boris; Klein, Karl Martin; Labauge, Pierre; LeGuern, Eric; Licchetta, Laura; Mei, Davide; Nava, Caroline; Pippucci, Tommaso; Rudolf, Gabrielle; Scheffer, Ingrid Eileen; Striano, Pasquale; Tinuper, Paolo; Zara, Federico; Corbett, Mark; Bahlo, Melanie

    2016-10-01

    Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder characterized by adult onset, involuntary muscle jerks, cortical myoclonus and occasional seizures. FAME is genetically heterogeneous with more than 70 families reported worldwide and five potential disease loci. The efforts to identify potential causal variants have been unsuccessful in all but three families. To date, linkage analysis has been the main approach to find and narrow FAME critical regions. We propose an alternative method, pedigree free identity-by-descent (IBD) mapping, that infers regions of the genome between individuals that have been inherited from a common ancestor. IBD mapping provides an alternative to linkage analysis in the presence of allelic and locus heterogeneity by detecting clusters of individuals who share a common allele. Succeeding IBD mapping, gene prioritization based on gene co-expression analysis can be used to identify the most promising candidate genes. We performed an IBD analysis using high-density single nucleotide polymorphism (SNP) array data followed by gene prioritization on a FAME cohort of ten European families and one Australian/New Zealander family; eight of which had known disease loci. By identifying IBD regions common to multiple families, we were able to narrow the FAME2 locus to a 9.78 megabase interval within 2p11.2-q11.2. We provide additional evidence of a founder effect in four Italian families and allelic heterogeneity with at least four distinct founders responsible for FAME at the FAME2 locus. In addition, we suggest candidate disease genes using gene prioritization based on gene co-expression analysis.

  9. Assignment of the locus for congenital lactase deficiency to 2q21, in the vicinity of but separate from the lactase-phlorizin hydrolase gene.

    PubMed

    Järvelä, I; Enattah, N S; Kokkonen, J; Varilo, T; Savilahti, E; Peltonen, L

    1998-10-01

    Congenital lactase deficiency (CLD) is an autosomal recessive, gastrointestinal disorder characterized by watery diarrhea starting during the first 1-10 d of life, in infants fed lactose-containing milks. Since 1966, 42 patients have been diagnosed in Finland. CLD is the most severe form of lactase deficiency, with an almost total lack of lactase-phlorizin hydrolase (LPH) activity on jejunal biopsy. In adult-type hypolactasia, the most common genetic enzyme deficiency in humans, this enzyme activity is reduced to 5%-10%. Although the activity of intestinal LPH has been found to be greatly reduced in both forms, the molecular pathogenesis of lactase deficiencies is unknown. On the basis of the initial candidate-gene approach, we assigned the CLD locus to an 8-cM interval on chromosome 2q21 in 19 Finnish families. At the closest marker locus, a specific allele 2 was present in 92% of disease alleles. On the basis of a genealogical study, the CLD mutation was found to be enriched in sparsely populated eastern and northern Finland, because of a founder effect. The results of both the genealogical study and the haplotype analysis indicate that one major mutation in a novel gene causes CLD in the Finnish population. Consequently, the critical region could be restricted further, to an approximately 350-kb interval, by ancient-haplotype and linkage-disequilibrium analyses. Surprisingly, the LPH gene was shown to lie outside the critical CLD region, excluding it as a causative gene for CLD. The LPH locus was found to reside >2 Mb from the critical CLD region.

  10. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

    PubMed Central

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

    2013-01-01

    Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

  11. Paracentric inversion of chromosome 7 (46,XX,inv(7)(q21.2q22)) in a newborn with hypoplastic left heart syndrome

    SciTech Connect

    Kuforjii, T.A.; Pillers, D.M.; Silberbach, M.

    1994-09-01

    Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease that is uniformly fatal without surgical intervention. Fetal echocardiography allows prenatal diagnosis, but this condition may not become apparent until after the mid-second trimester. We report a term baby with severe HLHS who had an 18 week fetal ultrasound that reportedly demonstrated a normal heart. There was no family history of congenital heart disease. She was phenotypically female with no dysmorphic features. Physical examination was otherwise normal. She expired at 48 hours of age. The autopsy was noncontributory. The karyotype was 46,XX, but there was an apparently balanced paracentric inversion of the long arm of chromosome 7 (46,XX,inv(7)(q21.2q22)). The mother`s chromosome study was normal without any inversion, and the father was not available for study. Hypoplastic left heart syndrome has been associated with extracardiac anomalies and chromosomal abnormalities including 45,XO,11q-, and trisomy 18. It has also been reported in 5 members spanning 3 generations of a family with a spectrum of left heart defects suggesting an autosomal dominant pattern with high penetrance. First-degree relatives of infants with HLHS have a thirteen percent incidence of related cardiovascular malformations, a frequency higher than predicted by a multifactorial model of inheritance, suggesting that at least a portion of HLHS have a genetic basis. Karyotype analysis, including high resolution banding, may help define the etiology of this condition. Chromosome 7 has not been implicated in HLHS. This case emphasizes the need for genetic analysis, including a pedigree, of affected families. It also underscores the importance of screening by karyotype analysis to determine whether defects of the long arm of chromosome 7 are important in the pathogenesis of hypoplastic left heart syndrome.

  12. Broader utilization of origins of DNA replication in cancer cell lines along a 78 kb region of human chromosome 2q34.

    PubMed

    Valenzuela, Manuel S; Hu, Lan; Lueders, John; Walker, Robert; Meltzer, Paul S

    2012-01-01

    Human DNA replication depends on the activation of thousands of origins distributed within the genome. The actual distribution of origins is not known, nor whether this distribution is unique to a cell type, or if it changes with the proliferative state of the cell. In this study, we have employed a real-time PCR-based nascent strand DNA abundance assay, to determine the location of origins along a 78 kb region on Chr2q34. Preliminary studies using nascent DNA strands isolated from either HeLa and normal skin fibroblast cells showed that in both cell lines peaks of high origin activity mapped in similar locations. However, the overall origin profile in HeLa cells corresponded to broad origin activation zones, whereas in fibroblasts a more punctuated profile of origin activation was observed. To investigate the relevance of this differential origin profile, we compared the origin distribution profiles in breast cancer cell lines MDA-MB-231, BT-474, and MCF-7, to their normal counterpart MCF-10A. In addition, the CRL7250 cell line was also used as a normal control. Our results validated our earlier observation and showed that the origin profile in normal cell lines exhibited a punctuated pattern, in contrast to broader zone profiles observed in the cancer cell lines. A quantitative analysis of origin peaks revealed that the number of activated origins in cancer cells is statistically larger than that obtained in normal cells, suggesting that the flexibility of origin usage is significantly increased in cancer cells compared to their normal counterparts.

  13. The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature.

    PubMed

    Urraca, Nora; Cleary, Julie; Brewer, Victoria; Pivnick, Eniko K; McVicar, Kathryn; Thibert, Ronald L; Schanen, N Carolyn; Esmer, Carmen; Lamport, Dustin; Reiter, Lawrence T

    2013-08-01

    Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum.

  14. Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study).

    PubMed

    Roten, Linda T; Johnson, Matthew P; Forsmo, Siri; Fitzpatrick, Elizabeth; Dyer, Thomas D; Brennecke, Shaun P; Blangero, John; Moses, Eric K; Austgulen, Rigmor

    2009-02-01

    Genome-wide scans in Icelandic, Australian/New Zealand and Finnish pedigrees have provided evidence for maternal susceptibility loci for pre-eclampsia on chromosome 2, although at different positions (Iceland: 2p13 and 2q23, Australia/New Zealand: 2p11-12 and 2q22, Finland: 2p25). In this project, a large population-based (n=65 000) nested case-control study was performed in Norway to further explore the association between positional candidate genes on chromosome 2q and pre-eclampsia, using single-nucleotide polymorphisms (SNPs). DNA samples from 1139 cases (women with one or more pre-eclamptic pregnancies) and 2269 controls (women with normal pregnancies) were genotyped using the Applied Biosystems SNPlex high-throughput genotyping assay. In total, 71 SNPs within positional candidate genes at 2q22-23 locus on chromosome 2 were genotyped in each individual. Genotype data were statistically analysed with the sequential oligogenic linkage analysis routines (SOLAR) computer package. Nominal evidence of association was found for six SNPs (rs1014064, rs17742134, rs1424941, rs2161983, rs3768687 and rs3764955) within the activin receptor type 2 gene (ACVR2A) (all P-values <0.05). The non-independence of statistical tests due to linkage disequilibrium between SNPs at a false discovery rate of 5% identifies our four best SNPs (rs1424941, rs1014064, rs2161983 and rs3768687) to remain statistically significant. The fact that populations with different ancestors (Iceland/Norway-Australia/New Zealand) demonstrate a common maternal pre-eclampsia susceptibility locus on chromosome 2q22-23, may suggest a general role of this locus, and possibly the ACVR2A gene, in pre-eclampsia pathogenesis.

  15. Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

    PubMed Central

    Wegiel, Jerzy; Frackowiak, Janusz; Mazur-Kolecka, Bozena; Schanen, N. Carolyn; Cook, Edwin H.; Sigman, Marian; Brown, W. Ted; Kuchna, Izabela; Wegiel, Jarek; Nowicki, Krzysztof; Imaki, Humi; Ma, Shuang Yong; Chauhan, Abha; Chauhan, Ved; Miller, David L.; Mehta, Pankaj D.; Flory, Michael; Cohen, Ira L.; London, Eric; Reisberg, Barry; de Leon, Mony J.; Wisniewski, Thomas

    2012-01-01

    Background It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount. Methodology/Principal Findings In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques. Conclusions/Significance The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic

  16. Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy

    PubMed Central

    Coughlin, Curtis R.; Geiger, Elizabeth A.; Salvador, Blake J.; Elias, Ellen R.; Cavanaugh, Jean L.; Chatfield, Kathryn C.; Miyamoto, Shelley D.; Shaikh, Tamim H.

    2016-01-01

    Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inherited TMEM87B mutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations in TMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role of TMEM87B in its etiology, especially the cardiac pathology. PMID:27148590

  17. A de novo 2q35-q36.1 deletion incorporating IHH in a Chinese boy (47,XYY) with syndactyly, type III Waardenburg syndrome, and congenital heart disease.

    PubMed

    Wang, D; Ren, G F; Zhang, H Z; Yi, C Y; Peng, Z J

    2016-12-02

    Reports of terminal and interstitial deletions of the long arm of chromosome 2 are rare in the literature. Here, we present a case report concerning a Chinese boy with a 47,XYY karyotype and a de novo deletion comprising approximately 5 Mb between 2q35 and q36.1, along with syndactyly, type III Waardenburg syndrome, and congenital heart disease. High-resolution chromosome analysis to detect copy number variations was carried out using an Affymetrix microarray platform, and the genes affected by the patient's deletion, including IHH, were determined. However, no copy number changes were observed in his healthy parents. The present case exhibited novel syndactyly features, broadening the spectrum of clinical findings observed in individuals with 2q interstitial deletions. Our data, together with previous observations, suggest that IHH haploinsufficiency is the principal pathogenic factor in the syndactyly phenotype in this study, and that different types of variations at the IHH locus may cause divergent disease phenotypes. This is the first report of the involvement of IHH haploinsufficiency in syndactyly phenotype.

  18. Female patient with autistic disorder, intellectual disability, and co-morbid anxiety disorder: Expanding the phenotype associated with the recurrent 3q13.2-q13.31 microdeletion.

    PubMed

    Quintela, Ines; Gomez-Guerrero, Lorena; Fernandez-Prieto, Montse; Resches, Mariela; Barros, Francisco; Carracedo, Angel

    2015-12-01

    In recent years, the advent of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays and its use as a first genetic test for the diagnosis of patients with neurodevelopmental phenotypes has allowed the identification of novel submicroscopic chromosomal abnormalities (namely, copy number variants or CNVs), imperceptible by conventional cytogenetic techniques. The 3q13.31 microdeletion syndrome (OMIM #615433) has been defined as a genomic disorder mainly characterized by developmental delay, postnatal overgrowth, hypotonia, genital abnormalities in males, and characteristic craniofacial features. Although the 3q13.31 CNVs are variable in size, a 3.4 Mb recurrently altered region at 3q13.2-q13.31 has been recently described and non-allelic homologous recombination (NAHR) mediated by flanking human endogenous retrovirus (HERV-H) elements has been suggested as the mechanism of deletion formation. We expand the phenotypic spectrum associated with this recurrent deletion performing the clinical description of a 9-year-old female patient with autistic disorder, total absence of language, intellectual disability, anxiety disorder and disruptive, and compulsive eating behaviors. The array-based molecular karyotyping allowed the identification of a de novo recurrent 3q13.2-q13.31 deletion encompassing 25 genes. In addition, we compare her clinical phenotype with previous reports of patients with neurodevelopmental and behavioral disorders and proximal 3q microdeletions. Finally, we also review the candidate genes proposed so far for these phenotypes.

  19. The gene for the serpin thrombin inhibitor (P17), protease nexin I, is located on human chromosome 2q33-q35 and on syntenic regions in the mouse and sheep genomes

    SciTech Connect

    Carter, R.E.; Burkin, D.J.; Fournier, R.E.K.

    1995-05-01

    Protease nexin I (PNI) is the most important physiologic regulator of {alpha}-thrombin in tissues. PNI is highly expressed and developmentally regulated in the nervous system where it is concentrated at neuromuscular junctions and also central synapses in the hippocampus and striatum. Approximately 10% of identified proteins at mammalian neuromuscular junctions are serine protease inhibitors, consistent with their central role in balancing serine protease activity to develop, maintain, and remodel synapses. Southern blot hybridization of PNI cDNA to somatic cell hybrids placed the structural gene for PNI (locus PI7) on human chromosome 2q33-q35 and to syntenic chromosomes in the mouse (chromosome 1) and sheep (chromosome 2). 30 refs., 2 figs.

  20. Distinction in binding of peptides (P2E) and its mutations (P2G, P2Q) to a graphene sheet via a hierarchical coarse-grained Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.; Farmer, B. L.

    2013-10-01

    A hierarchical coarse-grained approach is used to study the binding of peptides (P2E: 1E2P3L4Q5L6K7M) and variants (P2G: 1G2P3L4Q5L6K7M and P2Q: 1Q2L3P4M5E6K7L) with a graphene sheet. Simulation-based residue-substrate and hydropathy index-based residue-residue interaction is used as input to a phenomenological interaction potential for peptide chains to execute the stochastic motion with a graphene sheet at the center of a box. Large-scale Monte Carlo simulations are performed at a range (low to high) of temperatures to identify peptides binding with the graphene sheet with a constant peptide concentration (Cp = 0.01). A number of local (energy, mobility, and substrate contact profiles) and global (density profiles, mean square displacement of the center of mass of a peptide and its radius of gyration) physical quantities are examined to monitor the patterns. We find that each peptide can bind to a graphene sheet at low temperatures but the residues that can anchor their binding vary among these three peptides. For example, P2E is anchored by 1E, 4Q, and 6K, P2Q by 1Q, 5E, and 6K, and P2G by nearly all its residues with about the same strength except 1G and 2P. The site-specific binding is reflected in the thermal response of the radius of gyration of the peptides. Despite the lack of a large difference in binding patterns, a systematic variation in radius of gyration and surface binding profile with the temperature reveals the distinction in their binding: the probability of P2E binding is the highest and that of P2G is the lowest.

  1. Improved molecular diagnosis of unparental disomy 15 in Prader-Willi and Angelman syndromes utilizing new short tandem repeats (STRs) mapped to chromosome 15q11.2-q12

    SciTech Connect

    Christian, S.L.; Kubota, T.; Ledbetter, D.H.

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation disorders caused by paternal (PWS) or maternal (AS) deficiencies of chromosome 15q11.2-q12. Three STRs (D15S11, GABRB3, and D15S113) were previously developed utilizing YACs from this region as a molecular diagnostic test for PWS/AS. Since then twenty-three new STRs have been developed by several groups which map to 15q11.2-q12. Fine mapping of some of these markers was accomplished utilizing a 3.5 Mb YAC contig of this region. Three new CEPH-Genethon markers, D15S122, D15S128, and D15S210 were mapped within the smallest PWS/AS critical regions. D15S122 mapped to YACs 230H12 and 132D4, D15S128 mapped to YACs 457B4, 11H11, and B58C7, and D15S210 mapped to 132D4 and B230E3. To improve molecular diagnosis of uniparental disomy in PWS/AS, D15S122 and D15S128 with >70% hetrozygosities were placed in a new multiplex PCR reaction with D15S11. Additionally, three CEPH-Genethon markers with high heterozygosities from distal 15q, D15S123, D15S125, and D15S131, were used establish a second multiplex to increase the total number of markers analyzed to six. Twenty-three patients with uniparental disomy 15 were compared using the original multiplex and the two new multiplexes. The results indicated that 16/23 had at least one fully informative marker with the original multiplex and 23/23 using the two new multiplexes. Using a more rigorous diagnostic criterion of two fully informative markers, only 8/23 were informative with the original multiplex and 21/23 with the two new multiplexes. These results demonstrate that these two new multiplexes composed of a total of six polymorphic STRs provide an improved diagnostic test for uniparental disomy 15.

  2. Refinement of the deletion in 8q22.2-q22.3: the minimum deletion size at 8q22.3 related to intellectual disability and epilepsy.

    PubMed

    Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-ichi; Ida, Kazumi; Naruto, Takuya; Iai, Mizue; Kurosawa, Kenji

    2014-08-01

    Kuechler et al. [2011] reported five patients with interstitial deletions in 8q22.2-q22.3 who had intellectual disability, epilepsy, and dysmorphic features. We report on a new patient with the smallest overlapping de novo deletion in 8q22.3 and refined the phenotype. The proposita was an 8-year-old girl, who developed seizures at 10 months, and her epileptic seizure became severe and difficult to control with antiepileptic drugs. She also exhibited developmental delay and walked alone at 24 months. She was referred to us for evaluation for developmental delay and epilepsy at the age of 8 years. She had intellectual disability (IQ 37 at 7 years) and autistic behavior, and spoke two word sentences at 8 years. She had mild dysmorphic features, including telecanthus and thick vermilion of the lips. Array comparative genomic hybridization detected a 1.36 Mb deletion in 8q22.3 that encompassed RRM2B and NCALD, which encode the small subunit of p53-inducible ribonucleotide reductase and neurocalcin delta in the neuronal calcium sensor family of calcium-binding proteins, respectively. The minimum overlapping region between the present and previously reported patients is considered to be a critical region for the phenotype of the deletion in 8q22.3. We suggest that the deletion in 8q22.3 may represent a clinically recognizable condition, which is characterized by intellectual disability and epilepsy.

  3. Electroproduction of ppi+pi- off protons at 0.2<Q^2<0.6 GeV^2 and 1.3 < W < 1.57 GeV with CLAS.

    SciTech Connect

    Fedotov, Gleb; Mokeev, Viktor; Burkert, Volker; Elouadrhiri, Latifa; Golovach, Evgeny; Ishkhanov, Boris; Isupov, Evgeny; Shvedunov, Nikolay

    2009-01-01

    This paper reports on the most comprehensive data set obtained on differential and fully integrated cross sections for the process $e p \\rightarrow e' p \\pi^{+} \\pi^{-} $. The data were collected with the CLAS detector at Jefferson Laboratory. Measurements were carried out in the so-far unexplored kinematic region of photon virtuality 0.2 $<$ $Q^{2}$ $<$ 0.6 GeV$^{2}$ and invariant mass of the final hadron system $W$ from 1.3 to 1.57~GeV. For the first time, nine independent 1-fold differential cross sections were determined in each bin of $W$ and $Q^{2}$ covered by the measurements. A phenomenological analysis of the data allowed us to establish the most significant mechanisms contributing to the reaction. The non-resonant mechanisms account for a major part of cross-sections. However, we find sensitivity to s-channel excitations of low-mass nucleon resonances, especially to the $N(1440)P_{11}$ and $N(1520)D_{13}$ states in kinematical dependencies of the 1-fold

  4. Common variants at 2q37.3, 8q24.21, 15q21.3, and 16q24.1 influence chronic lymphocytic leukemia risk

    PubMed Central

    Crowther-Swanepoel, Dalemari; Broderick, Peter; Di Bernardo, Maria Chiara; Dobbins, Sara E; Torres, María; Mansouri, Mahmoud; Ruiz-Ponte, Clara; Enjuanes, Anna; Rosenquist, Richard; Carracedo, Angel; Jurlander, Jesper; Campo, Elias; Juliusson, Gunnar; Montserrat, Emilio; Smedby, Karin E; Dyer, Martin JS; Matutes, Estella; Dearden, Claire; Sunter, Nicola J; Hall, Andrew G; Mainou-Fowler, Tryfonia; Jackson, Graham H; Summerfield, Geoffrey; Harris, Robert J; Pettitt, Andrew R; Allsup, David J; Bailey, James R; Pratt, Guy; Pepper, Chris; Fegan, Chris; Parker, Anton; Oscier, David; Allan, James M; Catovsky, Daniel; Houlston, Richard S

    2016-01-01

    To identify novel risk variants for chronic lymphocytic leukemia (CLL) we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio [OR] = 1.39; P = 2.11 x 10-9), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10-10), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10-7) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10-7). There was also evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10-6) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10-6). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy. PMID:20062064

  5. A prenatally ascertained, maternally inherited 14.8 Mb duplication of chromosomal bands Xq13.2-q21.31 associated with multiple congenital abnormalities in a male fetus.

    PubMed

    Sismani, C; Donoghue, J; Alexandrou, A; Karkaletsi, M; Christopoulou, S; Konstantinidou, A E; Livanos, P; Patsalis, P C; Velissariou, V

    2013-11-01

    Duplications of the X chromosome are rare cytogenetic findings, and have been associated with an abnormal phenotype in the male offspring of apparently normal or near normal female carriers. We report on the prenatal diagnosis of a duplication on the long arm of chromosome X from chromosomal band Xq13.2 to q21.31 in a male fetus with increased nuchal translucency in the first trimester and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed additional chromosomal material in the long arm of chromosome X at position Xq13. Analysis with high resolution array CGH revealed the additional material is in fact a duplication of the region Xq13.2-q21.13. The duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022, ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and CHM. Analysis of the parents revealed the mother to be a carrier of the same duplication. After elected termination of the pregnancy at 28 weeks a detailed autopsy of the fetus allowed for genotype-phenotype correlations.

  6. Subtle familial translocation t(11;22)(q24.2;q13.33) resulting in Jacobsen syndrome and distal trisomy 22q13.3: further details of genotype-phenotype maps.

    PubMed

    Jamsheer, Aleksander; Smyk, Marta; Wierzba, Jolanta; Kołowska, Jolanta; Woźniak, Anna; Skołozdrzy, Joanna; Fischer, Maria; Latos-Bieleńska, Anna

    2008-01-01

    We report on 3 kindred patients with terminal 11q monosomy and distal 22q trisomy involving the SHANK3 gene, resulting from a subtle familial translocation t(11;22)(q24.2;q13.33). The patients presented with the characteristic symptoms of Jacobsen syndrome (JBS), including: mental retardation, short stature, and craniofacial dysmorphism in all 3 cases; cardiac defects in 2 cases; and thrombocytopenia, brain abnormality, eye coloboma, recurrent infections, cryptorchidism and toe anomalies in single cases. The oldest patient also had Hashimoto disease and diabetes mellitus type 2. So far, these 2 conditions have not been reported in adult patients with JBS. Features typical for distal 22q trisomy in our patients include muscular hypotonia and prenatal failure to thrive, seen in 2 and 1 cases, respectively. We also present a family member with 11q24.2-qter trisomy and 22q13.33-qter monosomy, whose clinical phenotype is partially overlapping with several dysmorphic features of JBS. In addition, multiple pregnancy losses and infantile deaths occurred in this family, suggesting that these chromosomal imbalances may produce a lethal phenotype. FISH with a panel of BAC probes determined the accurate sizes of the deletion 11q (9.9 Mb) and trisomy 22q (0.8 Mb). To date, only 5 cases of submicroscopic 22q13.3-qter trisomy have been reported. A detailed clinical description of our patients, along with a precise cytogenetic designation of chromosomal breakpoints, allow further refinement of genotype-phenotype correlation for distal imbalances in 11q and 22q.

  7. A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes 2q24, 5q33, 6p12, and 12p12.

    PubMed

    Asher, Julian E; Lamb, Janine A; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P

    2009-02-01

    Synesthesia, a neurological condition affecting between 0.05%-1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception.

  8. Ionization of molecular hydrogen and stripping of oxygen atoms and ions in collisions of Oq++H2 (q = 0- 8): Data for secondary electron production from ion precipitation at Jupiter

    NASA Astrophysics Data System (ADS)

    Schultz, D. R.; Ozak, N.; Cravens, T. E.; Gharibnejad, H.

    2017-01-01

    Energetic oxygen and sulfur ion precipitation into the atmosphere of Jupiter is thought to produce an X-ray aurora as well as to contribute to ionization, heating, and dissociation of the molecules of the atmosphere. At high energy, stripping of electrons from these ions by atmospheric gas molecules results in the production of high charge states throughout a portion of this passage through the atmosphere. Therefore, to enable modeling of the effects of secondary electrons produced by this ion precipitation, from either the solar wind or magnetospheric sources such as the Galilean moons, a large range of ionization and stripping data is calculated and tabulated here that otherwise is not available. The present data are for the abundant precipitating species, oxygen, colliding with the dominant upper atmosphere gas, molecular hydrogen, and cover the principal reaction channels leading to secondary electron production (single and double ionization, transfer ionization, and double capture followed by autoionization, and single and double stripping of electrons from the projectile). Since the ions possess initial energies at the upper atmosphere in the keV to MeV range, and are then slowed as they pass through the atmosphere, results are calculated for 1-2000 keV/u Oq++H2 (q =0-8). In addition to the total cross sections for ionization and stripping processes, models require the distribution in energy and angle of the ejected electrons, so cross sections differential in these parameters are also calculated. The data may be used to model the energy deposited by ion precipitation in Jupiter's atmosphere and thereby contribute to the elucidation of the ionosphere-atmosphere coupling.

  9. A Whole-Genome Scan and Fine-Mapping Linkage Study of Auditory-Visual Synesthesia Reveals Evidence of Linkage to Chromosomes 2q24, 5q33, 6p12, and 12p12

    PubMed Central

    Asher, Julian E.; Lamb, Janine A.; Brocklebank, Denise; Cazier, Jean-Baptiste; Maestrini, Elena; Addis, Laura; Sen, Mallika; Baron-Cohen, Simon; Monaco, Anthony P.

    2009-01-01

    Synesthesia, a neurological condition affecting between 0.05%–1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different aspect of the same modality. Familiality studies show evidence of a strong genetic predisposition; whereas initial pedigree analyses supported a single-gene X-linked dominant mode of inheritance with a skewed F:M ratio and a notable absence of male-to-male transmission, subsequent analyses in larger samples indicated that the mode of inheritance was likely to be more complex. Here, we report the results of a whole-genome linkage scan for auditory-visual synesthesia with 410 microsatellite markers at 9.05 cM density in 43 multiplex families (n = 196) with potential candidate regions fine-mapped at 5 cM density. Using NPL and HLOD analysis, we identified four candidate regions. Significant linkage at the genome-wide level was detected to chromosome 2q24 (HLOD = 3.025, empirical genome-wide p = 0.047). Suggestive linkage was found to chromosomes 5q33, 6p12, and 12p12. No support was found for linkage to the X chromosome; furthermore, we have identified two confirmed cases of male-to-male transmission of synesthesia. Our results demonstrate that auditory-visual synesthesia is likely to be an oligogenic disorder subject to multiple modes of inheritance and locus heterogeneity. This study comprises a significant step toward identifying the genetic substrates underlying synesthesia, with important implications for our understanding of the role of genes in human cognition and perception. PMID:19200526

  10. Deletion 2q: two new cases with karyotypes 46,XY,del(2)(q31q33) and 46,XX,del(2)(q36).

    PubMed Central

    Young, R S; Shapiro, S D; Hansen, K L; Hine, L K; Rainosek, D E; Guerra, F A

    1983-01-01

    We describe the clinical and cytogenetic findings of two patients with deletions of the long arm of chromosome 2. One has an interstitial deletion identical to that found in a previously reported patient, although they are phenotypically dissimilar. The other patient has a terminal deletion, the first such deletion reported to date. Images PMID:6876110

  11. An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9 Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family with an intrachromosomal 19p-into-19q between-arm insertion.

    PubMed

    Lybaek, Helle; Ørstavik, Karen Helene; Prescott, Trine; Hovland, Randi; Breilid, Harald; Stansberg, Christine; Steen, Vidar Martin; Houge, Gunnar

    2009-07-01

    In a 2 and a half-year-old girl with onset of puberty before the age of 5 months, short stature, hand anomalies and severe mental retardation, an 8.9 Mb interstitial 19p13 duplication containing 215 predicted genes was detected. It was initially assumed that the duplication involved the kisspeptin receptor gene, GPR54, known to stimulate induction of puberty, but more refined duplication mapping excluded this possibility. In an attempt to further understand the genotype-phenotype correlation, global gene expression was measured in skin fibroblasts. The overall expression pattern was quite similar to controls, and only about 25% of the duplicated genes had an expression level that was increased by more than 1.3-fold, with no obvious changes that could explain the precocious puberty. The proband's mother carried a balanced between-arm insertion of the duplicated segment that resembled a pericentric inversion. The same insertion was found in several other family members, including one who had lost a daughter with severe mental retardation and menarche at the age of 10 years. Another close relative was severely mentally retarded, but neither dysmorphic nor microcephalic. His phenotype was initially ascribed to a presumed cryptic chromosome 19 imbalance caused by the 19p-into19q insertion, but subsequent array-CGH detected a 3.9-Mb deletion of 2q23.3q24.1. This novel microdeletion involves seven genes, of which FMNL2, a suggested regulator of Rho-GTPases, and NR4A2, an essential gene for differentiation of dopaminergic neurons, may be critical genes for the proposed 2q23q24 microdeletion syndrome.

  12. Shorepower Truck Electrification Project (STEP) - 1Q - 2Q 2013

    SciTech Connect

    2014-02-01

    The Fleet Test and Evaluation Team at the U.S. Department of Energy's National Renewable Energy Laboratory is evaluating and documenting the use of shorepower at 50 planned American Recovery and Reinvestment Act (ARRA)-funded truck stop electrification (TSE) sites across the nation. Trucks participating in the study have idle-reduction equipment installed that was purchased with rebates through the ARRA. A total of 5,000 rebates will be approved. the ARRA. A total of 5,000 rebates will be approved.

  13. Q2/Q3 2016 Solar Industry Update

    SciTech Connect

    Feldman, David; Boff, Daniel; Margolis, Robert

    2016-10-11

    This technical presentation provides an update on the major trends that occurred in the solar industry in the Q2 and Q3 of 2016. Major topics of focus include global and U.S. supply and demand, module and system price, investment trends and business models, and updates on U.S. government programs supporting the solar industry.

  14. Genetics Home Reference: 2q37 deletion syndrome

    MedlinePlus

    ... 25 percent of people with this condition have autism, a developmental condition that affects communication and social ... Additional Information & Resources MedlinePlus (4 links) Health Topic: Autism Spectrum Disorder Health Topic: Developmental Disabilities Health Topic: ...

  15. Synthesizing new [(SnSe)1.15]m(TSe2)n, [(SnSe)1.16]m(VSe2)n[(SnSe)1.16]p(TaSe2)q, and (SnSe)1.16(V.51Ta.49Se2) intergrowth compounds (T = V and Ta)

    NASA Astrophysics Data System (ADS)

    Atkins, Ryan Elliot

    A modification of the modulated elemental reactants synthetic technique was developed and used to synthesize several new layered compounds. Several TSe2, [(SnSe)1+y] m(TSe2)n, [(SnSe) 1+y] m(TSe2) n[(SnSe)1+y]p(T'Se 2)q, and (SnSe)1+y(V 1-xTaxSe2) layered compounds were synthesized by the new modulated elemental reactant (MER) technique with T = V, Ta, and Ti. The MER approach is a low-temperature synthesis that allows the kinetic trapping of metastable compounds, allowing a designed synthesis with control over the value of m, n, p, and q. These layered compounds were structurally characterized by X-ray diffraction and transmission electron microscopy studies. Each integer increase of m, n, p, and q resulted in a linear increase in thickness, representing the single structural units of SnSe (a Sn/Se atomic bilayer) and TSe2 (an X-T-X trilayer sandwich). All of the compounds contained preferentially oriented layering, with the layer's (00l ) plane parallel to the substrate surface. From Bragg-Brentano and in-plane X-ray diffraction studies, the layers are found to be regularly spaced along c with abrupt interfaces and contain crystallinity in their ab-plane. Many of these layered compounds were found to exhibit turbostratic disorder, a random rotational disorder that is usually present in materials made by the MER technique. The presence of turbostratic disorder was found to be dependent on the polytypes that exist in the bulk form of the TSe2 constituent. The electrical properties of the layered compounds were studied by means of temperature-dependent resistivity and Hall measurements. Interesting electrical properties were found as a result of the turbostratic disorder, including a charge density wave transition found in the [(SnSe)1.15]m(VSe2) ferecrystal. The onset temperature of the CDW transition was found to be a sensitive function of the layering sequence, increasing with higher m values. The CDW transition was attributed to the VSe2 constituent and was

  16. Proteomic analysis of the Rett syndrome experimental model mecp2(Q63X) mutant zebrafish.

    PubMed

    Cortelazzo, Alessio; Pietri, Thomas; De Felice, Claudio; Leoncini, Silvia; Guerranti, Roberto; Signorini, Cinzia; Timperio, Anna Maria; Zolla, Lello; Ciccoli, Lucia; Hayek, Joussef

    2017-02-10

    Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Recently, a zebrafish carrying a mecp2-null mutation has been developed with the resulting phenotypes exhibiting defective sensory and thigmotactic responses, and abnormal motor behavior reminiscent of the human disease. Here, we performed a proteomic analysis to examine protein expression changes in mecp2-null vs. wild-type larvae and adult zebrafish. We found a total of 20 proteins differentially expressed between wild-type and mutant zebrafish, suggesting skeletal and cardiac muscle functional defects, a stunted glycolysis and depleted energy availability. This molecular evidence is directly linked to the mecp2-null zebrafish observed phenotype. In addition, we identified changes in expression of proteins critical for a proper redox balance, suggesting an enhanced oxidative stress, a phenomenon also documented in human patients and RTT murine models. The molecular alterations observed in the mecp2-null zebrafish expand our knowledge on the molecular cascade of events that lead to the RTT phenotype.

  17. De novo direct duplication of chromosome segment 22q11.2-q13.1

    SciTech Connect

    Fujimoto, Atsuko; Lin, Ming S.

    1996-03-29

    Lindsay et al. [1995] reported a case of de novo duplication of the segment 22q11-q12. Molecular cytogenetics studies showed that the segment includes the regions responsible for the {open_quotes}cat eye,{close_quotes} DiGeorge, and velo-cardio-facial syndrome, and extends distal to the breakpoint cluster region. The phenotype was milder than that of complete trisomy 22 and der(22)t(11;22) (q23;q11) syndrome and was similar in type and severity to that of {open_quotes}cat eye{close_quotes} syndrome (CES). They suggested that trisomy of gene(s) responsible for the CES might have a predominant phenotypic effect over other genes present in the region duplicated in their patient. 3 refs., 2 figs.

  18. 31 CFR 30.2 - Q-2: To what entities does this part apply?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... apply? 30.2 Section 30.2 Money and Finance: Treasury Office of the Secretary of the Treasury TARP... part applies to any TARP recipient, provided that the requirements of sections 111(b) (portions of § 30... the TARP remains outstanding. For a TARP recipient that has had an obligation to the...

  19. 31 CFR 30.2 - Q-2: To what entities does this part apply?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... apply? 30.2 Section 30.2 Money and Finance: Treasury Office of the Secretary of the Treasury TARP... part applies to any TARP recipient, provided that the requirements of sections 111(b) (portions of § 30... the TARP remains outstanding. For a TARP recipient that has had an obligation to the...

  20. 31 CFR 30.2 - Q-2: To what entities does this part apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... apply? 30.2 Section 30.2 Money and Finance: Treasury Office of the Secretary of the Treasury TARP... part applies to any TARP recipient, provided that the requirements of sections 111(b) (portions of § 30... the TARP remains outstanding. For a TARP recipient that has had an obligation to the...

  1. 31 CFR 30.2 - Q-2: To what entities does this part apply?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... apply? 30.2 Section 30.2 Money and Finance: Treasury Office of the Secretary of the Treasury TARP... part applies to any TARP recipient, provided that the requirements of sections 111(b) (portions of § 30... the TARP remains outstanding. For a TARP recipient that has had an obligation to the...

  2. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3.

    PubMed Central

    Greger, V; Knoll, J H; Wagstaff, J; Woolf, E; Lieske, P; Glatt, H; Benn, P A; Rosengren, S S; Lalande, M

    1997-01-01

    Angelman syndrome (AS) most frequently results from large (> or = 5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located approximately 25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within approximately 1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. Images Figure 2 Figure 3 PMID:9042916

  3. Monte Carlo simulation of a dynamical fermion problem: The light q sup 2 q sup 2 system

    SciTech Connect

    Grondin, G. . Dept. of Physics Oak Ridge National Lab., TN )

    1991-01-01

    We present results from a Guided Random Walk Monte Carlo simulation of the light q{sup 2}{bar q}{sup 2} system in a Coulomb-plus-linear quark potential model using an Intel iPSC/860 hypercube. A solvable model problem is first considered, after which we study the full q{sup 2}{bar q}{sup 2} system in (J,I) = (2,2) and (2,0) sectors. We find evidence for no bound states below the vector-vector threshold in these systems. 17 refs., 6 figs.

  4. Evidence for an exotic S= -2, Q= -2 baryon resonance in proton-proton collisions at the CERN SPS.

    PubMed

    Alt, C; Anticic, T; Baatar, B; Barna, D; Bartke, J; Betev, L; Białkowska, H; Billmeier, A; Blume, C; Boimska, B; Botje, M; Bracinik, J; Bramm, R; Brun, R; Buncić, P; Cerny, V; Christakoglou, P; Chvala, O; Cramer, J G; Csató, P; Darmenov, N; Dimitrov, A; Dinkelaker, P; Eckardt, V; Farantatos, G; Filip, P; Flierl, D; Fodor, Z; Foka, P; Freund, P; Friese, V; Gál, J; Gaździcki, M; Georgopoulos, G; Gładysz, E; Hegyi, S; Höhne, C; Kadija, K; Karev, A; Kniege, S; Kolesnikov, V I; Kollegger, T; Korus, R; Kowalski, M; Kraus, I; Kreps, M; van Leeuwen, M; Lévai, P; Litov, L; Makariev, M; Malakhov, A I; Markert, C; Mateev, M; Mayes, B W; Melkumov, G L; Meurer, C; Mischke, A; Mitrovski, M; Molnár, J; Mrówczyński, St; Pálla, G; Panagiotou, A D; Panayotov, D; Perl, K; Petridis, A; Pikna, M; Pinsky, L; Pühlhofer, F; Reid, J G; Renfordt, R; Retyk, W; Roland, C; Roland, G; Rybczyński, M; Rybicki, A; Sandoval, A; Sann, H; Schmitz, N; Seyboth, P; Siklér, F; Sitar, B; Skrzypczak, E; Stefanek, G; Stock, R; Ströbele, H; Susa, T; Szentpétery, I; Sziklai, J; Trainor, T A; Varga, D; Vassiliou, M; Veres, G I; Vesztergombi, G; Vranić, D; Wetzler, A; Włodarczyk, Z; Yoo, I K; Zaranek, J; Zimányi, J

    2004-01-30

    Results of resonance searches in the Xi(-)pi(-), Xi(-)pi(+), Xi;(+)pi(-), and Xi;(+)pi(+) invariant mass spectra in proton-proton collisions at sqrt[s]=17.2 GeV are presented. Evidence is shown for the existence of a narrow Xi(-)pi(-) baryon resonance with mass of 1.862+/-0.002 GeV/c(2) and width below the detector resolution of about 0.018 GeV/c(2). The significance is estimated to be above 4.2sigma. This state is a candidate for the hypothetical exotic Xi(--)(3/2) baryon with S=-2, I=3 / 2, and a quark content of (dsdsū). At the same mass, a peak is observed in the Xi(-)pi(+) spectrum which is a candidate for the Xi(0)(3/2) member of this isospin quartet with a quark content of (dsus[-]d). The corresponding antibaryon spectra also show enhancements at the same invariant mass.

  5. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

    SciTech Connect

    Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M.

    1997-03-01

    Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

  6. Mosaic marker chromosome 16 resulting in 16q11.2-q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia.

    PubMed

    Zerem, Ayelet; Vinkler, Chana; Michelson, Marina; Leshinsky-Silver, Esther; Lerman-Sagie, Tally; Lev, Dorit

    2011-12-01

    Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia.

  7. Velocardiofacial syndrome in father and daughter: What is the mechanism for the deletion 22(q11.2q11.2) in only the daughter?

    SciTech Connect

    Magenis, R.E.; Gunter, K.; Toth-Fejel, S.

    1994-09-01

    E.G. had marked feeding difficulty noted at birth; the cause was determined to be a paralyzed palate. In 1992 chromosome studies were performed because of the provisional diagnosis of velocardiofacial syndrome, and a small interstitial deletion of chromosome 22 was found. Recently the family was seen in our Genetics Clinic. The father had unusual facial features shared by his daughter, a paralyzed upper lip and a history of repaired Tetralogy of Fallot. His chromosomes appeared normal. FISH studies were performed on the child`s peripheral blood using the ONCOR DiGeorge region probe (D22S75) and the deletion verified. However, the father`s chromosomes were not deleted for the ONCOR probe (D22S75) and probe DO832 sent to us by Peter Scambler. Skin cells were then obtained and no deletion was detected in a total of 66 cells examined using both probes. Several questions arise from these data: does the father have velocardiofacial syndrome? Does he have occult mosaicism? Does he have a molecular deletion not detected by the probes used? And was this deletion somehow {open_quotes}amplified{close_quotes} in his daughter?

  8. Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

    PubMed Central

    Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, André G.; Marsman, Roos F.; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W.; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J.; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W. H. Linda; Psaty, Bruce M.; Tomaselli, Gordon F.; Sotoodehnia, Nona; Siscovick, David S.; Burke, Greg L.; Marbán, Eduardo; Spooner, Peter M.; Cupples, L. Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y. Antero; Wilde, Arthur A. M.; Tardif, Jean-Claude; O'Donnell, Christopher J.; Bezzina, Connie R.; Virmani, Renu; Stricker, Bruno H. C. h.; Tan, Hanno L.; Albert, Christine M.; Chakravarti, Aravinda; Rioux, John D.; Huikuri, Heikki V.; Chugh, Sumeet S.

    2011-01-01

    Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). PMID:21738491

  9. Room-temperature synthesis of CuInQ2 (Q = S or Se) in non-aqueous solution using an organoindium reagent

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Andras, Maria T.; Landry, Christopher C.; Barron, Andrew R.

    1994-01-01

    We have discovered a novel two-phase synthesis of CuInSe2 at 25 deg C from Cu2Se and (C5H5)3In in 4-methylpyridine (4-MePy). An analogous reaction to produce CuInS2 must be run at 140 deg C in refluxing 4-MePy in the presence of 2-mercaptopyridine. Microscopy of CuInSe2 produced at 25 deg C shows it to be platelet-shaped crystallites with an approximate particle size of 10 microns, less than 2 percent C and H, with a small amount of unidentified crystalline impurity. Our results demonstrate that it is possible to produce from solution a material that is ordinarily synthesized in bulk or films at much higher temperatures or using extraneous reagents and/or electrons.

  10. Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

    SciTech Connect

    Vamvakopoulos, N.C.; Sioutopoulou, T.O.; Durkin, S.A.

    1995-01-01

    Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

  11. In situ localization of the genetic locus encoding the lysosomal acid lipase/cholesteryl esterase (LIPA) deficient in wolman disease to chromosome 10q23. 2-q23. 3

    SciTech Connect

    Anderson, R.A.; Rao, N.; Byrum, R.S.; Rothschild, C.B.; Bowden, D.W.; Hayworth, R.; Pettenati, M. )

    1993-01-01

    Human acid lipase/cholesteryl esterase (EC 3.1.1.13) is a 46-kDa glycoprotein required for the lysosomal hydrolysis of cholesteryl esters and triglycerides that cells acquire through the receptor-mediated endocytosis of low-density lipoproteins. This activity is essential in the provision of free cholesterol for cell metabolism as well as for the feedback signal that modulates endogenous cellular cholesterol production. The extremely low level of lysosomal acid lipase in patients afflicted with the hereditary, allelic lysosomal storage disorders Woman disease (WD) and cholesteryl ester storage disease (CESD) (MIM Number 278000 (6)) is associated with the massive intralysosomal lipid storage and derangements in the regulation of cellular cholesterol production (10). Both WD and CESD cells lack a specific acid lipase isoenzyme and it is thought that the different mutations associated with WD and CESD are in the structural gene for this isoenzyme, LIPA. Analysis of the activity of the acid lipase isoenzyme in cell extracts from human-Chinese hamster somatic cell hybrids (4, 11) demonstrated the concordant segregation of the gene locus for lysosomal acid lipase with the glutamate oxaloacetate transaminase-1 (GOT1) enzyme marker for human chromosome 10 which was subsequently localized to 10q24.1 q25.1 (8). 11 refs., 1 figs.

  12. Transformed aggressive γδ-variant T-cell large granular lymphocytic leukemia with acquired copy neutral loss of heterozygosity at 17q11.2q25.3 and additional aberrations.

    PubMed

    Zhang, Ling; Ramchandren, Radhakrishnan; Papenhausen, Peter; Loughran, Thomas P; Sokol, Lubomir

    2014-09-01

    T-cell large granular lymphocytic leukemia (T-LGLL) is a rare indolent lymphoproliferative disorder characterized by cytopenias, splenomegaly, and various degrees of T-cell lymphocytosis, due to a clonal expansion of CD8-positive cytotoxic T-cells. Phenotypic variants of T-LGLL include CD4(+) /CD8(-) T-cells, with dual CD4(-) /CD8(-) /γδ(+) T-cells being even rarer. Cytogenetic abnormalities in T-LGLL have rarely been reported, and there is scientific debate regarding the existence of aggressive or transformed variants of T-LGLL. We report a patient with T-LGLL, γδ variant, with nearly 20-year-long duration of cytopenias before transformation to an unusual clinical scenario, manifesting with marked lymphocytosis >100 × 10(9) /L and infiltration of lymph nodes, tonsils, and subcutaneous tissue. Single-nucleotide polymorphism assays revealed acquired copy neutral loss of heterozygosity at 17q and deletion of 3p21.31, in addition to trisomy 5, monosomy X, and monosomy 21. These genetic abnormalities provided a better understanding of the molecular nature and the potentiality of disease transformation.

  13. Further delineation of the phenotype maps for partial trisomy 16q24 and Jacobsen syndrome by a subtle familial translocation t(11;16)(q24.2;q24.1).

    PubMed

    Zahn, Susanne; Ehrbrecht, Antje; Bosse, Kristin; Kalscheuer, Vera; Propping, Peter; Schwanitz, Gesa; Albrecht, Beate; Engels, Hartmut

    2005-11-15

    We report on two cases of distal monosomy 11q and partial trisomy 16q due to a familial subtle translocation detected by FISH subtelomere screening. Exact breakpoint analyses by FISH with panels of BAC probes demonstrated a 9.3-9.5 megabase partial monosomy of 11q24.2-qter and a 4.9-5.4 megabase partial trisomy of 16q24.1-qter. The index patient displayed craniofacial dysmorphisms, mild mental retardation and postnatal growth retardation, muscular hypotonia, mild periventricular leukodystrophy, patent ductus arteriosus, thrombocytopenia, recurrent infections, inguinal hernia, cryptorchidism, pes equinovarus, and hearing deficiencies. In his mother's cousin who bears the identical unbalanced translocation, mild mental retardation, patent ductus arteriosus, hypogammaglobulinemia, recurrent infections, unilateral kidney hypoplasia, pes equinovarus, and hearing deficiencies were reported. Since only four descriptions of cryptic or subtle partial trisomies 16q have been published to date, our patients contribute greatly to the delineation of the phenotype of this genomic imbalance. In contrast to this, terminal deletions of the long arm of chromosome 11 cause a haploinsufficiency disorder (Jacobsen syndrome) in which karyotype-phenotype correlations are already being established. Here, our findings contribute to the refinement of a phenotype map for several Jacobsen syndrome features including abnormal brain imaging, renal malformations, thrombocytopenia/pancytopenia, inguinal hernia, testicular ectopy, pes equinovarus, and hearing deficiency.

  14. Localization of the genes encoding the melanocortin-2 (Adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11. 2 and 20q13. 2-q13. 3 by fluorescence in situ hybridization

    SciTech Connect

    Gantz, I.; Tashiro, Takao; Konda, Yoshitaka; Shimoto, Yoshimasa; Miwa, Hiroto; Munzert, G.; Barcroft, C.; Glover, T.; Yamada, Tadataka )

    1993-10-01

    Adrenocorticotropic hormone (ACTH) and [alpha]-, [beta]-, and [gamma]-melanocyte-stimulating hormone (MSH) are products of propiomelanocortin post-translational processing. These compounds are collectively labeled as melanocortins (MC). Aside from their established effects on the regulation of the adrenal cortex (ACTH) and melanocytes ([alpha]-MSH), the melanocortins have been implicated in a broad array of physiological events. Melanocortins mediate their effects through cell membrane receptors belonging to the superfamily of seven transmembrane G-protein-linked receptors. Using the technique of polymerase chain reaction with primers based on conserved areas of the seven transmembrane G-protein-linked receptor family, the authors recently isolated an [open quotes]orphan[close quotes] subfamily of this receptor group. Within the past year, two of these receptors were identified as specific for [alpha]-MSH (MC1) and ACTH (MC2). They have recently described a third melanocortin receptor (MC3) that appears to recognize the core heptapeptide sequence of melanocortins with equal potency and efficacy and identified its presence in the brain, placenta, and gut. Using the FISH technique, they localized the ACTH and the melanocortin-3 receptors to chromosome loci 18p11.2 and 20q12.3-q13.2, respectively. 19 refs., 1 fig.

  15. A novel pseudo-dicentric variant of 16p11.2-q11.2 contains euchromatin from 16p11.2-p11.1 and resembles pathogenic duplications of proximal 16q.

    PubMed

    Barber, J C K; Brasch-Andersen, C; Maloney, V K; Huang, S; Bateman, M S; Graakjaer, J; Heinl, U D; Fagerberg, C

    2013-01-01

    An unusually large G-light band between 2 G-dark bands in the proximal long arm of chromosome 16 was found in a boy of 5 years of age ascertained with growth retardation, microcephaly, and dysmorphic features. Dual color bacterial artificial chromosome fluorescence in situ hybridization (BAC FISH) and oligonucleotide array comparative genomic hybridization (oaCGH) were used to show that these bands contained a euchromatic duplication of a minimum of 940 kb between base pairs 34,197,413-35,137,025 in 16p11.2-p11.1 as well as a duplication of the centromere and major 16qh/16p11.2 heterochromatic block, covering a minimum of 12.3 Mb. The same pseudo-dicentric chromosome was found in the father who has attention deficit hyperactivity disorder (ADHD). The euchromatic region is not known to be subject to imprinting and overlaps multiple large copy number variations (CNVs) in the Database of Genomic Variants as well as similar CNVs that are benign or of uncertain significance in the International Standards for Cytogenomic Arrays database. We conclude that this family has a novel pseudo-dicentric euchromatic variant of chromosome 16 that is unlikely to be the cause of the variable phenotype in father and son but needs to be distinguished from heterochromatic variants or pathogenic duplications of proximal 16q.

  16. A yeast artificial chromosome contig and NotI restriction map that spans the tumor suppressor gene(s) locus, 11q22.2-q23.3

    SciTech Connect

    Arai, Yasuhito; Hosoda, Fumie; Nakayama, Kyoko; Ohki, Misao

    1996-07-01

    Human chromosome 11q22-q23 is a pathologically important region in which a high level of loss of heterozygosity has been reported for breast, ovary, cervical, colon, and lung carcinomas, malignant melanomas, and hematologic malignancies. This strongly indicates that one or more tumor suppressor genes reside within the deleted region. In this report, we report the development of a contig map that covers most of the deleted regions found in these malignancies. The map comprises a contig of 66 overlapping yeast artificial chromosomes (YACs) and spans a region of 17 Mb from the PGR gene at 11q22.2 to the MLL gene at q23.3. In the process of screening the YACs, 50 new sequence-tagged site markers were developed from the termini of the YAC inserts. These markers were used for chromosome walking, and the data were then integrated into the contig map. NotI sites in the region. Using 22 of them, a NotI restriction map of the region from PGR to D11S939 was developed. This YAC contig will provide efficient tools for identification of the putative tumor suppressor gene(s). 49 refs., 3 figs., 2 tabs.

  17. A Cluster-Randomized Controlled Trial Evaluating the Effectiveness and Cost-Effectiveness of Tobacco Cessation on Prescription in Swedish Primary Health Care: A Protocol of the Motivation 2 Quit (M2Q) Study

    PubMed Central

    Lindgren, Peter; Sundberg, Carl Johan; Petzold, Max; Tomson, Tanja

    2016-01-01

    Background In Sweden, the prevalence of tobacco use is disproportionately high among socioeconomically disadvantaged groups. Previous research and clinical experience suggest that prescribed lifestyle interventions in the primary health care (PHC) setting such as Physical Activity on Prescription are effective in changing behavior. However, there is a lack of evidence for if and how such a prescription approach could be effectively transferred into the tobacco cessation context. Objective The aim of this trial is to evaluate the effectiveness and cost-effectiveness of Tobacco Cessation on Prescription (TCP) compared to current practice for tobacco cessation targeting socioeconomically disadvantaged groups in the PHC setting in Sweden. Methods The design is a pragmatic cluster-randomized controlled trial. The sample will consist of 928 daily tobacco users with Swedish social security numbers and permanent resident permits, recruited from 14-20 PHC centers located in socioeconomically disadvantaged areas in Stockholm County. The primary outcome will be measured in self-reported 7-day abstinence at 6 and 12 months after the intervention. The secondary outcomes will be measured in daily tobacco consumption, number of quit attempts, and health-related quality of life at 6 and 12 months after the intervention. Data will be collected through questionnaires and review of electronic medical records. Cost-effectiveness will be estimated through decision analytic modeling and measured by the incremental cost per quality-adjusted life year. Results In the first set of PHC centers participating in the study, eight centers have been included. Recruitment of individual study participants is currently ongoing. Inclusion of a second set of PHC centers is ongoing with expected study start in September 2016. Conclusions If TCP is found effective and cost-effective compared to standard treatment, the method could be implemented to facilitate tobacco cessation for socioeconomically disadvantaged groups in the PHC setting in Sweden. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 11498135; http://www.isrctn.com/ISRCTN11498135 (Archived by WebCite at http://www.webcitation.org/6kTu6giYQ) PMID:27637517

  18. Pre- and postnatal findings in a patient with a novel rec(8)dup(8q)inv(8)(p23.2q22.3) associated with San Luis Valley syndrome.

    PubMed

    Vera-Carbonell, Ascensión; López-González, Vanesa; Bafalliu, Juan Antonio; Piñero-Fernández, Juan; Susmozas, Joaquín; Sorli, Moisés; López-Pérez, Rocío; Fernández, Asunción; Guillén-Navarro, Encarna; López-Expósito, Isabel

    2013-09-01

    San Luis Valley syndrome, which is due to a recombinant chromosome 8 (SLV Rec8) found in Hispanic individuals from Southwestern United States, is a well-established syndrome associated with intellectual disabilities and, frequently, severe cardiac anomalies. We report for the first time on a Moroccan girl with a recombinant chromosome 8 prenatally diagnosed as SLV Rec8 by conventional cytogenetic studies. At birth, an oligo array-CGH (105 K) defined the breakpoints and the size of the imbalanced segments, with a deletion of ≈ 2.27 Mb (8p23.2-pter) and a duplication of ≈ 41.93 Mb (8q22.3-qter); thus this recombinant chromosome 8 differed from that previously reported in SLV Rec8 syndrome. The phenotypic characteristics associated with this SLV Rec8 genotype overlap those commonly found in patients with 8q duplication reported in the literature. We review SLV Rec8 and other chromosome 8 aberrations and suggest that the overexpression of cardiogenic genes located at 8q may be the cause of the cardiac defects in this patient.

  19. De novo interstitial duplication of 15q11.2-q13.1 with complex maternal uniparental trisomy for the 15q11-q13 region in a patient with Prader-Willi syndrome.

    PubMed

    Burrage, Lindsay C; Person, Richard E; Flores, Angela; Villanos, Maria Theresa M; Bi, Weimin; Wiszniewska, Joanna; Bacino, Carlos A

    2012-10-01

    Prader-Willi syndrome is caused by the lack of paternal contribution for the imprinted 15q11-q13 region that originates through a number of mechanisms such as paternal deletion of 15q11-q13, maternal uniparental disomy, or by an imprinting defect due to epimutations in the paternal imprinting center. In the present report, we describe a female patient with complex maternal uniparental trisomy for the 15q11-q13 Prader-Willi syndrome critical region due to a de novo interstitial duplication of 15q11-q13 region that is present in one of the maternal homologs. As a result, the patient has three maternally derived copies of the Prader-Willi syndrome critical region and absence of paternal 15 contribution and thus, presents with a Prader-Willi syndrome phenotype with risk for developing additional phenotypes (e.g., autism and psychiatric phenotypes) characteristic of maternally derived duplications of this region. We suggest that this is a rather unique mechanism leading to Prader-Willi syndrome that has not been previously reported.

  20. Measurement of the Deuteron Spin Structure Function g{sub 1}{sup d}(x) for 1 (GeV/c){sup 2} < Q{sup 2} < 40 (GeV/c){sup 2}

    SciTech Connect

    Perry Anthony; R.G. Arnold; Todd Averett; H.R. Band; M.C. Berisso; H. Borel; Peter Bosted; Stephen Bueltmann; M. Buenerd; T. Chupp; Steve Churchwell; G.R. Court; Donald Crabb; Donal Day; Piotr Decowski; P. DePietro; R. Erbacher; R. Erickson; Andrew Feltham; Helene Fonvieille; Emil Frlez; R. Gearhart; V. Ghazikhanian; Javier Gomez; Keith Griffioen; C. Harris; M.A. Houlden; E.W. Hughes; Charles Hyde-Wright; G. Igo; Sebastien Incerti; John Jensen; J.R. Johnson; Paul King; Yu.G. Kolomensky; Sebastian Kuhn; Richard Lindgren; R.M. Lombard-Nelsen; Jacques Marroncle; James Mccarthy; Paul McKee; W. Meyer; G.S. Mitchell; Joseph Mitchell; Michael Olson; S. Penttila; Gerald Peterson; Gerassimos Petratos; R. Pitthan; Dinko Pocanic; R. Prepost; C. Prescott; Liming Qin; Brian Raue; D. Reyna; L.S. Rochester; Stephen Rock; Oscar Rondon-Aramayo; Franck Sabatie; Ingo Sick; T. Smith; L. Sorrell; F. Staley; S. St. Lorant; L.M. Stuart; Z. Szalata; Y. Terrien; William Tobias; Luminita Todor; T. Toole; S. Trentalange; Dieter Walz; Robert Welsh; Frank Wesselmann; T.R. Wright; C.C. Young; Markus Zeier; Hong Guo Zhu; Benedikt Zihlmann

    1999-09-30

    New measurements are reported on the deuteron spin structure function g{sub 1}{sup d}. These results were obtained from deep inelastic scattering of 48.3 GeV electrons on polarized deuterons in the kinematic range 0.01 < x < 0.9 and 1 < Q{sup 2} < 40 (GeV/c){sup 2}. These are the first high dose electron scattering data obtained using lithium deuteride ({sup 6}Li{sup 2}H) as the target material. Extrapolations of the data were performed to obtain moments of g{sub 1}{sup d}, including {Gamma}{sub 1}{sup d}, and the net quark polarization {Delta} {Sigma}.

  1. An infant with a mosaic 45,X/46,X,psu dic(Y) (pter {r_arrow} q11.2::q11.2 {r_arrow}pter) karyotype and mixed gonadal dysgenesis studied for extent of mosaicism in the gonads

    SciTech Connect

    Reddy, K.S.; Sulcova, V.; Ho, C.K.; Conner, E.D.; Khurana, A.

    1996-12-30

    An infant with mixed gonadal dysgenesis was found to have a 45,X/46,X,psu dic(Y) karyotype. A low level (8%) of mosaicism for the dic(Y) cell line was observed in peripheral blood lymphocytes and skin fibroblasts. The dicentric nature of the Y chromosome became apparent in fluorescence in situ hybridization studies. The presence of Y centromeric sequences was demonstrated in the paraffin-embedded testis and streak ovary sections. The ratio of Y-positive cells was higher in the testis than in the streak ovary. 7 refs., 2 figs.

  2. Three-region specific microdissection libraries for the long arm of human chromosome 2, regions q33-q35, q31-q32, and q23-q24

    SciTech Connect

    Yu, J.; Tong, S.; Whittier, A.

    1995-09-01

    Three region-specific libraries have been constructed from the long arm of human chromosome 2, including regions 2q33-35 (2Q2 library), 2q31-32 (2Q3) and 2q23-24 (2Q4). Chromosome microdissection and the MboI linker-adaptor microcloning techniques were used in constructing these libraries. The libraries comprised hundreds of thousands of microclones in each library. Approximately half of the microclones in the library contained unique or low-copy number sequence inserts. The insert sizes ranged between 50 and 800 bp, with a mean of 130-190 bp. Southern blot analysis of individual unique sequence microclones showed that 70-94% of the microclones were derived from the dissected region. 31 unique sequence microclones from the 2Q2 library, 31 from 2Q3, and 30 from 2Q4, were analyzed for insert sizes, the hybridizing genomic HindIII fragment sizes, and cross-hybridization to rodent species. These libraries and the short insert microclones derived from the libraries should be useful for high resolution physical mapping, sequence-ready reagents for large scale genomic sequencing, and positional cloning of disease-related genes assigned to these regions, e.g. the recessive familial amyotrophic lateral sclerosis assigned to 2q33-q35, and a type I diabetes susceptibility gene to 2q31-q33. 17 refs., 5 figs., 2 tabs.

  3. Consent Agreement and Final Order for AMVAC Chemical Corporation

    EPA Pesticide Factsheets

    EPA has reason to believe that the pesticide Fluensulfone 480EC (a/k/a Nimitz) is misbranded as defined in section 2(q)(1)(F) of FIFRA, 7 U.S.C. § 136(q)(1)(F) and section 2(q)(1)(G) of FIFRA, 7 U.S.C. § 136(q)(1)(G).

  4. Brief Report: Peculiar Evolution of Autistic Behaviors in Two Unrelated Children with Brachidactyly-Mental Retardation Syndrome

    ERIC Educational Resources Information Center

    Mazzone, Luigi; Vassena, Lia; Ruta, Liliana; Mugno, Diego; Galesi, Ornella; Fichera, Marco

    2012-01-01

    Brachidactyly-Mental Retardation (BDMR) Syndrome (MIM 600430) is associated with terminal deletions at chromosome 2q37 and a limited number of studies also reported an association between 2q37 [right arrow] qter deletion and autism. Herein we describe two cases of autism in unrelated children with BDMR Syndrome, showing physical, cognitive,…

  5. Delivery of QTIiv2 Question Types

    ERIC Educational Resources Information Center

    Wills, Gary B.; Davis, Hugh C.; Gilbert, Lester; Hare, Jonathon; Howard, Yvonne; Jeyes, Steve; Millard, David; Sherratt, Robert

    2009-01-01

    The IMS Question and Test Interoperability (QTI) standard identifies 16 different question types which may be used in online assessment. While some partial implementations exist, the R2Q2 project has developed a complete solution that renders and responds to all 16 question types as specified. In addition, care has been taken in the R2Q2 project…

  6. 76 FR 15046 - Office of Hazardous Materials Safety; Notice of Application for Special Permits

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ...-DOT Okeechobee, FL. specification inside metal container similar to a DOT specification 2Q for the...) commerce of anhydrous hydrogen fluoride in a DOT 112S500I car with a minimum shell thick- thickness of...

  7. PRN 75-5: Unacceptable Use of the Word Chlorine in the Name and Labeling of Pesticides

    EPA Pesticide Factsheets

    Use of the word CHLORINE on labels other than in products containing liquified chlorine under pressure has been determined to be in violation of Section 2(q)(l)(A) of the Federal Insecticide, Fungicide, and Rodenticide Act.

  8. Host-guest complexation of cucurbit[8]uril with two enantiomers

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Zheng; Lin, Rui-Lian; Bai, Dong; Tao, Zhu; Liu, Jing-Xin; Xiao, Xin

    2017-03-01

    Host-guest complexation of cucurbit[8]uril (Q[8]) with two enantiomers, D-3-(2-naphthyl)-alanine (D-NA) and L-3-(2-naphthyl)-alanine (L-NA), has been fully investigated. Experimental data indicate that double guests reside within the cavity of Q[8] in both aqueous solution and solid state, generating highly stable homoternary complexes D-NA2@Q[8] and L-NA2@Q[8].

  9. Host-guest complexation of cucurbit[8]uril with two enantiomers

    PubMed Central

    Gao, Zhong-Zheng; Lin, Rui-Lian; Bai, Dong; Tao, Zhu; Liu, Jing-Xin; Xiao, Xin

    2017-01-01

    Host-guest complexation of cucurbit[8]uril (Q[8]) with two enantiomers, D-3-(2-naphthyl)-alanine (D-NA) and L-3-(2-naphthyl)-alanine (L-NA), has been fully investigated. Experimental data indicate that double guests reside within the cavity of Q[8] in both aqueous solution and solid state, generating highly stable homoternary complexes D-NA2@Q[8] and L-NA2@Q[8]. PMID:28300189

  10. Formal-Language-Theoretic Control & Coordination of Mobile Robots

    DTIC Science & Technology

    2007-10-29

    Control Specification q1 q2 q3 qA (−1) qB (+1) +1 +1 +1 −1 −1 −1 qA3 qA1 qA2 qB2 qB3 qB1 1/0.4 1/0.2 0/0.6 0/0.8 1/0.3 0/0.70/0.6 1/0.2 0/0.8 1/0.4 1...qB2 qB3 qB1 1/0.4 1/0.2 0/0.6 0/0.8 1/0.3 0/0.70/0.6 1/0.2 0/0.8 1/0.4 1/0.3 0/0.7 qA3 qA1 qA2 qB2 qB3 qB1 1/0.9 1/0.9 0/0.3 0/0.3 1/0.7 0/0.10/0.1 1

  11. Synthesis of Structured Macroporous TiO2 Thin Films and Investigation on Their Photocatalytic Activities

    NASA Astrophysics Data System (ADS)

    Kamegawa, Takashi; Suzuki, Norihiko; Yamashita, Hiromi

    2011-10-01

    Synthesis of structured macroporous TiO2 thin films on quartz substrate (macro-TiO2/Q) was performed by a dip-coating method using poly(methyl methacrylate) (PMMA) microspheres as template. Obtained TiO2 thin films kept high transparency and had anatase crystalline structure. SEM observations revealed that the macropores were uniformly formed on the film surface. The size of macropores was quite similar to the diameter of PMMA microspheres as template. In comparison to the nonporous TiO2 thin films (TiO2/Q), macro-TiO2/Q exhibited twice higher photocatalytic activity for decolorization of methylene blue in water. Decomposition of acetaldehyde in gas phase also proceeded efficiently on macro-TiO2/Q. Moreover, the surface of macro-TiO2/Q was easily hydrophilized after a short period of UV light irradiation and maintained lower water contact angle in the dark for a long period as compared to those of TiO2/Q.

  12. Genome-wide significant risk associations for mucinous ovarian carcinoma

    PubMed Central

    Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  13. Transverse space-charge effects in the AGS booster during injection

    SciTech Connect

    Colton, E.P.; Shi, D.; Parsa, Z.

    1988-04-29

    We have analyzed the transverse motion for 200 MeV protons under strong space-charge conditions. We considered up to 5 /times/ 10/sup 12/ protons per bunch; for the assumed distribution this corresponds to a maximum tune shift of /minus/0.75. We utilized single particle tracking to study the motion in normalized phase space as a function of initial particle amplitude. Subsequent FFT analyses were used to obtain the fractional betatron tunes at different z values along the bunch. The motion shows x /minus/ y coupling due to the so-called Montague resonance (2Q/sub x//minus/2Q/sub y//equals/0). Perturbations arise when particles have tunes in the neighborhood of the 2Q /equals/ 9 half-integral resonances but losses do not occur. It appears that the motion is stabilized simply due to the strong amplitude dependence of the tunes. 2 refs., 5 figs., 4 tabs.

  14. Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma

    SciTech Connect

    Turc-Carel, C.; Cin, P.D.; Limon, J.; Rao, U.; Li, F.P.; Corson, J.M.; Zimmerman, R.; Parry, D.M.; Cowan, J.M.; Sandberg, A.A.

    1987-04-01

    A translocation that involves chromosome X (band p11.2) and chromosome 18 (band q11.2) was observed in short-term in vitro cultures of cells from five synovial sarcomas and one malignant fibrous histiocytoma. In four of these tumors, the translocation t(X;18)(p11.2;q11.2) was reciprocal. The two other tumors had complex translocations: t(X;18;21)(p11.2;q11.2;p13) and t(X;15;18)(p11.2;q23;q11.2). A translocation between chromosomes X and 18 was not detected in other histological types of soft tissue sarcoma. The X;18 rearrangement appears to characterize the synovial sarcoma and is the first description of a primary, nonrandom change in the sex chromosome of a human solid tumor.

  15. Array comparative genomic hybridization analysis of olfactory neuroblastoma.

    PubMed

    Guled, Mohamed; Myllykangas, Samuel; Frierson, Henry F; Mills, Stacey E; Knuutila, Sakari; Stelow, Edward B

    2008-06-01

    Olfactory neuroblastoma is an unusual neuroectodermal malignancy, which is thought to arise at the olfactory membrane of the sinonasal tract. Due to its rarity, little is understood regarding its molecular and cytogenetic abnormalities. The aim of the current study is to identify specific DNA copy number changes in olfactory neuroblastoma. Thirteen dissected tissue samples were analyzed using array comparative genomic hybridization. Our results show that gene copy number profiles of olfactory neuroblastoma samples are complex. The most frequent changes included gains at 7q11.22-q21.11, 9p13.3, 13q, 20p/q, and Xp/q, and losses at 2q31.1, 2q33.3, 2q37.1, 6q16.3, 6q21.33, 6q22.1, 22q11.23, 22q12.1, and Xp/q. Gains were more frequent than losses, and high-stage tumors showed more alterations than low-stage olfactory neuroblastoma. Frequent changes in high-stage tumors were gains at 13q14.2-q14.3, 13q31.1, and 20q11.21-q11.23, and loss of Xp21.1 (in 66% of cases). Gains at 5q35, 13q, and 20q, and losses at 2q31.1, 2q33.3, and 6q16-q22, were present in 50% of cases. The identified regions of gene copy number change have been implicated in a variety of tumors, especially carcinomas. In addition, our results indicate that gains in 20q and 13q may be important in the progression of this cancer, and that these regions possibly harbor genes with functional relevance in olfactory neuroblastoma.

  16. Stability and Degradation Mechanisms of Metal-Organic Frameworks Containing the Zr6O4(OH)4 Secondary Building Unit

    DTIC Science & Technology

    2013-03-18

    shows the appearance of peaks at 2Q z 30.5 and 35.0, which are indic- ative of the (111) and the (200) planes of tetragonal zirconia respectively. As...and (200) planes of monoclinic zirconia respectively.28 The transition from an amorphous phase to the tetragonal phase and nally to the monoclinic...show the presence of new XRD peaks. These peaks are in good agreement with the XRD pattern of monoclinic zirconia . The peaks at 2Q z 17.5, 25.1, and

  17. Finite-size effect of η-deformed AdS5 × S5 at strong coupling

    NASA Astrophysics Data System (ADS)

    Ahn, Changrim

    2017-04-01

    We compute Lüscher corrections for a giant magnon in the η-deformed (AdS5×S5)η using the su(2 | 2) q-invariant S-matrix at strong coupling and compare with the finite-size effect of the corresponding string state, derived previously. We find that these two results match and confirm that the su(2 | 2) q-invariant S-matrix is describing world-sheet excitations of the η-deformed background.

  18. Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's disease.

    PubMed

    Tang, Bin; Seredenina, Tamara; Coppola, Giovanni; Kuhn, Alexandre; Geschwind, Daniel H; Luthi-Carter, Ruth; Thomas, Elizabeth A

    2011-06-01

    R6/2 transgenic mice with expanded CAG repeats (>300) have a surprisingly prolonged disease progression and longer lifespan than prototypical parent R6/2 mice (carrying 150 CAGs); however, the mechanism of this phenotype amelioration is unknown. We compared gene expression profiles in the striatum of R6/2 transgenic mice carrying ~300 CAG repeats (R6/2(Q300) transgenic mice) to those carrying ~150 CAG repeats (R6/2(Q150) transgenic mice) and littermate wildtype controls in order to identify genes that may play determinant roles in the time course of phenotypic expression in these mice. Of the top genes showing concordant expression changes in the striatum of both R6/2 lines, 85% were decreased in expression, while discordant expression changes were observed mostly for genes upregulated in R6/2(Q300) transgenic mice. Upregulated genes in the R6/2(Q300) mice were associated with the ubiquitin ligase complex, cell adhesion, protein folding, and establishment of protein localization. We qPCR-validated increases in expression of genes related to the latter category, including Lrsam1, Erp29, Nasp, Tap1, Rab9b, and Pfdn5 in R6/2(Q300) mice, changes that were not observed in R6/2 mice with shorter CAG repeats, even in late stages (i.e., 12 weeks of age). We further tested Lrsam1 and Erp29, the two genes showing the greatest upregulation in R6/2(Q300) transgenic mice, for potential neuroprotective effects in primary striatal cultures overexpressing a mutated human huntingtin (htt) fragment. Overexpression of Lrsam1 prevented the loss of NeuN-positive cell bodies in htt171-82Q cultures, concomitant with a reduction of nuclear htt aggregates. Erp29 showed no significant effects in this model. This is consistent with the distinct pattern of htt inclusion localization observed in R6/2(Q300) transgenic mice, in which smaller cytoplasmic inclusions represent the major form of insoluble htt in the cell, as opposed to large nuclear inclusions observed in R6/2(Q150) transgenic mice

  19. Multiloop Calculus in P-Adic String Theory and Bruhat-Tits Trees

    NASA Astrophysics Data System (ADS)

    Chekhov, L. O.; Mironov, A. D.; Zabrodin, A. V.

    We treat the open p-adic string world sheet as a coset space F=T/Γ, where T is the Bruhat-Tits tree for the p-adic linear group GL(2, Q p) and Γ⊂PGL(2, Q p) is some Schottky group. The boundary of this world sheet corresponds to p-adic Mumford curve of finite genus. The string dynamics is governed by the local gaussian action on the tree T. We find the amplitudes for emission processes of the tachyon states from the boundary.

  20. [New perspectives in the approach to diabetic macular edema. Aflibercept therapy].

    PubMed

    Ruiz-Moreno, J M

    2015-03-01

    The VISTA and VIVID trials were conducted to compare the safety and efficacy of two intravitreal injection (IVI) regimens of aflibercept versus macular laser photocoagulation for the treatment of diabetic macular edema (DME). These double-masked, phase III clinical trials randomized (461/402) patients with DME to receive either 2mg aflibercept IVI every 4 weeks (2q4) or 2mg aflibercept IVI every 8 weeks (2q8) after 5 initial monthly doses vs macular laser photocoagularion. The primary efficacy endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 52. Secondary efficacy endpoints were the change in central retinal thickness (CRT), the proportion of patients who gained ≥10 amd ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the change in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in near and distance vision. The mean BCVA gains in the 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (p<0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (p<0.0001) in VIVID. The proportions of patients gaining ≥ 15 letters and the proportion of patients with an improvement of > 2 levels in the severity of diabetic retinopathy was significant in the treatment groups versus the laser group. Mean reductions in CRT in the 2q4 and 2q8 groups vs the laser group were 185.9 and 183.1 versus 73.3 μm (p<0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (p<0.0001) in VIVID. The incidences of ocular and nonocular adverse events were similar in all groups. In conclusion, IIV aflibercept demonstrated statistically significant superiority in improvement in BCVA and reduction in DME over laser, with similar efficacy in the 2q4 and 2q8 groups in VISTA and VIVID.

  1. The Learning Principal[R]. Volume 5, Number 2

    ERIC Educational Resources Information Center

    Crow, Tracy, Ed.

    2009-01-01

    "The Learning Principal" is an eight-page newsletter published eight times a year. It focuses on the important and unique work of school principals. This issue includes: (1) Data Analysis Is a Courageous Look in the Mirror (Valerie von Frank); (2) Q&A: Opening Doors, Opening Minds (Valerie von Frank); (3) Focus on NSDC's [National Staff…

  2. The Learning Principal[R]. Volume 4, Number 8

    ERIC Educational Resources Information Center

    von Frank, Valerie, Ed.

    2009-01-01

    "The Learning Principal" is an eight-page newsletter published eight times a year. It focuses on the important and unique work of school principals. This issue includes: (1) Efficacy Can Overcome Classroom Barriers (Valerie von Frank); (2) Q & A: Leadership, Learning Communities Change School Culture (Valerie von Frank); (3) Focus on NSDC's…

  3. The Learning Principal[R]. Volume 5, Number 1

    ERIC Educational Resources Information Center

    von Frank, Valerie, Ed.

    2009-01-01

    "The Learning Principal" is an eight-page newsletter published eight times a year. It focuses on the important and unique work of school principals. This issue includes: (1) Framework "for" Improvement: Effective School Leadership Translates into Increased Student Learning (Valerie von Frank); (2) Q & A: Instructional…

  4. REAL-TIME MEASUREMENT OF AIRWAY RESPONSES TO SULOFUR DIOXIDE (SO2) IN AN INTACT, AWAKE GUINEA PIG MODEL

    EPA Science Inventory

    Real-time measurment of airway responses to Sulfur Dioxide (SO2) in an intact, awake guinea pig model. J Stanek1,2, Q Krantz2, J Nolan2, D Winsett2, W Watkinson2, and D Costa2. 1College of Veterinary Medicine, NCSU, Raleigh, NC, USA; 2Pulmonary Toxicology Branch, ETD, NHEERL, US...

  5. 42 CFR 414.1001 - Basis of payment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... is paid to a pharmacy for the first prescription of drugs and biologicals described in sections 1861(s)(2)(J), 1861(s)(2)(Q), and 1861(s)(2)(T) of the Act, that the pharmacy provided to a beneficiary during a 30-day period. (2) A supplying fee of $16 is paid to a pharmacy for each prescription...

  6. 42 CFR 414.1001 - Basis of payment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... is paid to a pharmacy for the first prescription of drugs and biologicals described in sections 1861(s)(2)(J), 1861(s)(2)(Q), and 1861(s)(2)(T) of the Act, that the pharmacy provided to a beneficiary during a 30-day period. (2) A supplying fee of $16 is paid to a pharmacy for each prescription...

  7. 42 CFR 414.1001 - Basis of payment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... is paid to a pharmacy for the first prescription of drugs and biologicals described in sections 1861(s)(2)(J), 1861(s)(2)(Q), and 1861(s)(2)(T) of the Act, that the pharmacy provided to a beneficiary during a 30-day period. (2) A supplying fee of $16 is paid to a pharmacy for each prescription...

  8. Effect of twice quenching and tempering on the mechanical properties and microstructures of SCRAM steel for fusion application

    NASA Astrophysics Data System (ADS)

    Xiong, Xuesong; Yang, Feng; Zou, Xingrong; Suo, Jinping

    2012-11-01

    The effect of twice quenching and tempering on the mechanical properties and microstructures of SCRAM steel was investigated. The results from tensile tests showed that whether twice quenching and tempering processes(1253 K/0.5 h/W.C(water cool) + 1033 K/2 h/A.C(air cool) + 1233 K/0.5 h/W.C + 1033 K/2 h/A.C named after 2Q&2TI, and 1253 K/0.5 h/W.C + 1033 K/2 h/A.C + 1233 K/0.5 h/W.C + 1013 K/2 h/A.C named after 2Q&2TII)increased strength of steel or not depended largely on the second tempering temperature compared to quenching and tempering process(1253 K/0.5 h/W.C + 1033 K/2 h/A.C named after 1Q&1T). Charpy V-notch impact tests indicated that twice quenching and tempering processes reduced the ductile brittle transition temperature (DBTT). Microstructure inspection revealed that the prior austenitic grain size and martensite lath width were refined after twice quenching and tempering treatments. Precipitate growth was inhibited by a slight decrease of the second tempering temperature from 1033 to 1013 K. The finer average size of precipitates is considered to be the main possible reason for the higher strength and lower DBTT of 2Q&2TII compared with 2Q&2TI.

  9. Gender-Based Violence Prevention. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on gender-based violence prevention. This issue contains the following articles: (1) Preventing Gender-Based Violence: An Overview (Linda Langford); (2) Q&A With Amelia Cobb; (3) Denim Day at HBCUs; (4) Dear Colleague Letter; (5) ED Grants for Violence Prevention; and (6) Higher Education Center…

  10. The Poisson-Boltzmann theory for the two-plates problem: some exact results.

    PubMed

    Xing, Xiang-Jun

    2011-12-01

    The general solution to the nonlinear Poisson-Boltzmann equation for two parallel charged plates, either inside a symmetric electrolyte, or inside a 2q:-q asymmetric electrolyte, is found in terms of Weierstrass elliptic functions. From this we derive some exact asymptotic results for the interaction between charged plates, as well as the exact form of the renormalized surface charge density.

  11. Earthquake Characteristics and Earthquake-Explosion Discrimination

    DTIC Science & Technology

    1979-01-01

    than a function of exponential order ( Lathi , 1968). The Q filter is an exponential defined by -wT/2Q A=A e (8) where T is travel time and QE is...Res., 1977. Lathi , B.P., Communication Systems, John Wiley and Sons, New York, 1968. Liu, H.P., D.L. Anderson, and H. Kanamori, Velocity dispersion

  12. 42 CFR 414.1001 - Basis of payment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... a pharmacy for the first prescription of drugs and biologicals described in sections 1861(s)(2)(J), 1861(s)(2)(Q), and 1861(s)(2)(T) of the Act, that the pharmacy provided to a beneficiary during a 30-day period. (2) A supplying fee of $16 is paid to a pharmacy for each prescription following the...

  13. 42 CFR 414.1001 - Basis of payment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... a pharmacy for the first prescription of drugs and biologicals described in sections 1861(s)(2)(J), 1861(s)(2)(Q), and 1861(s)(2)(T) of the Act, that the pharmacy provided to a beneficiary during a 30-day period. (2) A supplying fee of $16 is paid to a pharmacy for each prescription following the...

  14. Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease.

    PubMed

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco; Miraglia del Giudice, Emanuele; Nobili, Valerio

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis.Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD.CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage.We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02).Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.

  15. Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis. Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD. CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage. We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02). Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage. PMID:22927922

  16. Validation of linkage between BCWD resistance and spleen size QTL on Omy19 in rainbow trout: Pleiotropy versus linkage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial cold water disease (BCWD) is caused by infection with Flavobacterium psychrophilum, and results in significant economic losses in salmonid aquaculture. Previously, we identified a major QTL for BCWD resistance on Omy19 (h2q=0.57-0.67) as well as a QTL for surrogate measures of disease resi...

  17. A twin sibling with Prader-Willi syndrome caused by type 2 microdeletion following assisted reproductive technology: A case report

    PubMed Central

    HAN, JI YOON; PARK, JOONHONG; JANG, WOORI; CHAE, HYOJIN; KIM, MYUNGSHIN; KIM, YONGGOO

    2016-01-01

    Prader-Willi syndrome (PWS) is a neurobehavioral imprinting disorder, which arises due to an absence of paternally expressed genes within the 15q11.2-q13 region. This occurs via one of the three main genetic mechanisms, as follows: Deletion of the paternally inherited 15q11.2-q13 region, maternal uniparental disomy and imprinting defect. Recent studies have reported an association between imprinting disorders and assisted reproductive technologies (ART). The current study presents a 6-year-old female patient who is a dizygotic twin, in which one was born with de novo microdeletion at 15q11.2-q13.1 following in vitro fertilization. The patient had characteristic facial features including narrow bifrontal diameter, strabismus, downturned mouth, feeding problems and generalized hypotonia during infancy, developmental delay, mental retardation and rapid weight gain. Based upon phenotypic resemblance and the medical records, methylation-specific multiplex ligation-dependent probe amplification and array-based comparative genome hybridization analyses demonstrate type 2 microdeletion between breaking point 2 (BP2) and BP3, which occur from MKRN3 through HERC2 at 15q11.2-q13.1. To the best of our knowledge, the present study is the first to report a PWS case born following ART reported in South Korea. In addition to previous studies, the present study contributes to the consensus regarding genotype-phenotype comparisons in this respect. PMID:27330749

  18. Technical Evaluation of the RHS 200 for High Speed Ferry Applications and Coast Guard Missions

    DTIC Science & Technology

    1983-12-01

    GUARD THE NATIONAL TECHNICAL INFORMATION SERVICE ,, FERRY SERVICE SERVICE , SPRIN(;IELD. VIRGINIA 22161 RHS 200 PERFORMANCE EVALUATION S~tiett 14 .1 . s...TOE FERRY SERVICE EVALUATION INCLUDED SHIP COMPLIANCE WITH USCG APPLICABLE REQUIREMENIS AND OPERATIONAL AND ARRANGEMENT INFORMATION PERTINENT TO FERkY...Maintenpnce Cost fttimat.e ............................. o. 165 2q - Niqhliqhts of Passenqer Service Reliability, Maintainahility avid Availabiltity Per

  19. Comparison of gull-specific assays targeting 16S rRNA gene of Catellicoccus marimammalium and Streptococcus spp.

    EPA Science Inventory

    Gulls have been implicated as a source of fecal contamination in inland and coastal waters. Only one gull-specific assay is currently available (i.e., gull2 qPCR assay). This assay is based on the 16S rRNA gene of Catellicocclls marimammalium and has showed a high level of host-s...

  20. Improved Analysis Algorithms for UXO Filler Identification

    DTIC Science & Technology

    2009-02-01

    ratio SPectrum Interpolation and DEconvolution Routine Thermal neutron analysis Tri- nitro toluene Technic~r Support Working Group micro Curies...pairs has similar chemical composition. 40 "" ,. I) I il.2 Q,3 0 .. O".S ~ (<\\) Histogram of confidence vallll.’ . (b) Probabili ty of COffee I

  1. Synergistic extraction equilibrium of gallium(III) with di(2-ethylhexyl)phosphoric acid and 8-quinolinol derivatives into supercritical carbon dioxide.

    PubMed

    Ohashi, Akira; Kawashima, Natsumi; Sato, Kazuaki; Kim, Haeng-Boo

    2013-01-01

    The synergistic effect of five 8-quinolinol derivatives (HQs) on the extraction of gallium(III) with di(2-ethylhexyl)-phosphoric acid (D2EHPA or HA) from weak nitric acid into supercritical carbon dioxide (SC-CO(2)) was investigated. 8-Quinolinol (Hq), 5-ethoxymethyl-8-quinolinol (HO(2)q), 5-hexyloxymethyl-8-quinolinol (HO(6)q), 5-(2,2,2-trifluoroethoxymethyl)-8-quinolinol (HFO(2)q), and 5-chloro-8-quinolinol (5-Cl-Hq) were used as synergists. Synergism was observed for all of the HQs. The synergistic effect increased in the following order: Hq < HO(2)q < HFO(2)q < 5-Cl-Hq ≍ HO(6)q. The extent of synergism can be related to both the distribution constant and the acid dissociation constant of the HQ. The synergistic extraction equilibrium of gallium(III) with D2EHPA and 5-Cl-Hq into SC-CO(2) was investigated; the results suggest that the composition of the extracted complex is as GaA(2)Q·HA. The synergistic extraction mechanism was the same for both SC-CO(2) and n-heptane. The synergistic extraction equilibrium constants in both cases were calculated based on the experimental results.

  2. Runtime Monitoring and Verification of Systems with Hidden Information

    DTIC Science & Technology

    2012-02-01

    RV using UML-based statechart assertions. Section 3 provides an overview of HMM’s and HMM related algorithms . Section 4 describes our proposed...state sequence Q = q1 q2...qT? 3. How do we calculate the model parameters = (A,B, ) to maximize P(O| )? The most well known algorithms used to

  3. Tools for Large Graph Mining

    DTIC Science & Technology

    2005-06-01

    Edo , Leonid, Anya, Jason, and all others for their help and insights; and finally to Krishna, old friend, for his constant “Are you done yet?” which...17 3.4.1 (Q1) Accuracy of dynamical system ...4.4.1 (Q1) Accuracy of the dynamical system . . . . . . . . . . . . . . . . . . . 33 4.4.2 (Q2) Accuracy of the threshold condition

  4. "Give Me a Name for What's Wrong with Him": A Case Study of a Rare Chromosome Disorder

    ERIC Educational Resources Information Center

    Gilmore, Linda; Campbell, Marilyn

    2006-01-01

    The case is presented of a young boy with a rare chromosome disorder involving an interstitial deletion on chromosome 16 (16q11.2q13). Background information on chromosome disorders is presented along with a review of previous findings about the developmental consequences of chromosome 16q deletions. The case description illustrates the…

  5. Periodic and chaotic behaviors in optical bistability

    NASA Astrophysics Data System (ADS)

    Chen, Li-xue; Li, Chun-fei; Hong, Jing

    1984-11-01

    The periodic and chaotic behaviors for both long and short delay time are demonstrated successfully using a hybrid OBD. The degree of stability S is introduced into the dynamic equations of optical bistability with a delayed feedback. The instability threshold is S = 2 for long delay time and S = 1 + π/2Q for short delay time.

  6. Superposition of super-integrable pseudo-Euclidean potentials in N = 2 with a fundamental constant of motion of arbitrary order in the momenta

    NASA Astrophysics Data System (ADS)

    Campoamor-Stursberg, R.

    2014-04-01

    It is shown that for any α,β in {R} and kin {Z}, the Hamiltonian Hk=p1p2 -α q2^{(2k+1)}q1^{(-2k-3)}-β /2 q2kq1^{(-k-2)} is super-integrable, possessing fundamental constants of motion of degrees 2 and 2k + 2 in the momenta.

  7. Community Colleges--Prevention Challenges. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This issue of "Issues in Prevention" focuses on prevention challenges facing community colleges. This issue contains the following articles: (1) Prevention at Community Colleges; (2) Q&A With William Auvenshine; (3) Chancellor's Initiative at the University of Wisconsin-Stout; (4) Alcohol Marketing in the Digital Age; and (5) Higher Education…

  8. Drug Abuse on College Campuses: Emerging Issues. Issues in Prevention

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2012

    2012-01-01

    This "Issues in Prevention" focuses on emerging issues concerning drug abuse on college campuses. This issue contains the following articles: (1) Drug Abuse Trends; (2) Q&A With Jim Lange; (3) Bath Salts; (4) Refuse to Abuse; (5) Related Federal Resource; and (6) Higher Education Center Resources.

  9. Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2.

    PubMed

    Tammachote, Rachaneekorn; Kingsuwannapong, Nelawat; Tongkobpetch, Siraprapa; Srichomthong, Chalurmpon; Yeetong, Patra; Kingwatanakul, Pornchai; Monico, Carla G; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

    2012-09-01

    Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the alanine:glyoxylate aminotransferase (AGXT) gene, located on chromosome 2q37. Mutant AGXT leads to excess production and excretion of oxalate, resulting in accumulation of calcium oxalate in the kidney, and progressive loss of renal function. Brachydactyly mental retardation syndrome (BDMR) is an autosomal dominant disorder, caused by haploinsufficiency of histone deacetylase 4 (HDAC4), also on chromosome 2q37. It is characterized by skeletal abnormalities and developmental delay. Here, we report on a girl who had phenotypes of both PH1 and BDMR. PCR-sequencing of the coding regions of AGXT showed a novel missense mutation, c.32C>G (p.Pro11Arg) inherited from her mother. Functional analyses demonstrated that it reduced the enzymatic activity to 31% of the wild-type and redirected some percentage of the enzyme away from the peroxisome. Microsatellite and array-CGH analyses indicated that the proband had a paternal de novo telomeric deletion of chromosome 2q, which included HDAC4. To our knowledge, this is the first report of PH1 and BDMR, with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2q.

  10. Abusing the privelege to care: shame on us.

    PubMed

    Churchill, Karin M

    Ian Peate, Consultant Editor of BJN, wrote the editorial 'Abusing the privelege: to care - shame on us' which was adapted and published on the BBC website (http://tinyurl.com/6cf2q5t). There was an overwhelming response to Ian's piece and some examples are shown here.

  11. Chromosomal localization of the human diazepam binding inhibitor gene

    SciTech Connect

    DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

    1988-09-01

    The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the /gamma/-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes.

  12. Chromosome region-specific libraries for human genome analysis. Final progress report, 1 March 1991--28 February 1994

    SciTech Connect

    Kao, F.T.

    1994-04-01

    The objectives of this grant proposal include (1) development of a chromosome microdissection and PCR-mediated microcloning technology, (2) application of this microtechnology to the construction of region-specific libraries for human genome analysis. During this grant period, the authors have successfully developed this microtechnology and have applied it to the construction of microdissection libraries for the following chromosome regions: a whole chromosome 21 (21E), 2 region-specific libraries for the long arm of chromosome 2, 2q35-q37 (2Q1) and 2q33-q35 (2Q2), and 4 region-specific libraries for the entire short arm of chromosome 2, 2p23-p25 (2P1), 2p21-p23 (2P2), 2p14-p16 (wP3) and 2p11-p13 (2P4). In addition, 20--40 unique sequence microclones have been isolated and characterized for genomic studies. These region-specific libraries and the single-copy microclones from the library have been used as valuable resources for (1) isolating microsatellite probes in linkage analysis to further refine the disease locus; (2) isolating corresponding clones with large inserts, e.g. YAC, BAC, P1, cosmid and phage, to facilitate construction of contigs for high resolution physical mapping; and (3) isolating region-specific cDNA clones for use as candidate genes. These libraries are being deposited in the American Type Culture Collection (ATCC) for general distribution.

  13. The global cell therapy industry continues to rise during the second and third quarters of 2012.

    PubMed

    Mason, Chris; McCall, Mark J; Culme-Seymour, Emily J; Suthasan, Shalini; Edwards-Parton, Simon; Bonfiglio, Gregory A; Reeve, Brock C

    2012-12-07

    During Q2-Q3 2012, the cell therapy industry benefited from a number of positive external influences including advantageous changes to future FDA regulation, but stock market activity was highly mixed. The FDA approved two more products and an appreciable number of public-company-sponsored clinical trials are progressing through phases 1-3.

  14. Photocopy of drawing (this photograph is an 8" x 10" ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing (this photograph is an 8" x 10" copy of an 8" x 10" negative; 1875 original architectural drawing located at NARA) Officers quarters US Navy Yard Pensacola, partition wall quarters B, C,D,E,H,K,M - U.S. Naval Air Station, Senior Officers' Quarters Q-2, Q-2 North Avenue, Pensacola, Escambia County, FL

  15. Spectroscopic Observation of Comet P/de Vico: Comparison with P/Halley and P/Brorsen-Metcalf

    NASA Astrophysics Data System (ADS)

    Kawakita, Hideyo; Ayani, Kazuya; Matsubara, Keiji

    1998-06-01

    A spectroscopic observation of Comet P/de Vico in the visible region was made at Bisei Astronomical Observatory on 1995 October 11. The obtained spectrum covers the wavelengths from 5200 to 7200 Angstroms, and includes several emissions, such as C_2, NH_2, and [O I]. The ratios of the gas-production rates of C_2 and NH_2 relative to that of H_2O, Q(C_2)/Q(H_2O), and Q(NH_2)/Q(H_2O), were determined from our observation based on the Haser model. The production-rate ratio and gas-to-dust ratio were: Q(C_2)/Q(H_2O) = 0.25%, Q(NH_2)/Q(H_2O) = 0.14%, and log_ {10}[ Q(H_2O)/Af rho ] = 26.9 at the time of observation. Comet P/de Vico was similar to P/Halley from the viewpoint of the chemical composition (C_2 and NH_2 relative to the H_2O), and P/de Vico was comparable to P/Brorsen-Metcalf concerning the gas-to-dust ratio. P/de Vico was one of the most gas-rich comets ever known.

  16. Waardenberg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS consortium

    PubMed Central

    Farrer, Lindsay A.; Grundfast, Kenneth M.; Amos, Jean; Arnos, Kathleen S.; Asher, James H.; Beighton, Peter; Diehl, Scott R.; Fex, Jörgen; Foy, Carole; Friedman, Thomas B.; Greenberg, Jacquie; Hoth, Christopher; Marazita, Mary; Milunsky, Aubrey; Morell, Robert; Nance, Walter; Newton, Valerie; Ramesar, Rajkumar; Agustin, Theresa B. San; Skare, James; Stevens, Cathy A.; Wagner, Ronald G.; Wilcox, Edward R.; Winship, Ingrid; Read, Andrew P.

    1992-01-01

    Previous studies have localized the gene for Waardenburg syndrome (WS) type I to the distal portion of chromosome 2q, near the ALPP locus. We pooled linkage data obtained from 41 WS type I and 3 WS type II families which were typed for six polymorphic loci on chromosome 2q in order to refine the location of the WS locus (WS1) and evaluate the extent of genetic heterogeneity. In the course of this work, we developed diagnostic criteria for genetic and phenotypic studies. Our findings, based on two-locus and multilocus analysis using a linkage map established from reference pedigrees, suggest that there are two or more mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q, between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each marker, respectively. The results also indicate that WS1 is responsible for the illness in approximately 45% of all families in this sample. However, the odds favoring this position over a location between ALPP and SAG are only 2:1 when alternate assumptions about the proportion of linked families are considered. We conclude that a more saturated map of this region of chromosome 2q, including highly polymorphic markers, will be needed to accurately distinguish linked families and, ultimately, isolate the mutant gene. PMID:1349198

  17. 40 CFR 162.156 - General requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... thereunder: (i) Sec. 12(a)(1) (A) through (E), in accordance with: (A) Sec. 2(q)(1) (A) through (G). (B) Sec... registered by the Administrator in accordance with sec. 7 of FIFRA and 40 CFR part 167. (c) Books and...

  18. 26 CFR 1.509(a)-5 - Special rules of attribution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... described in subparagraph (1) of this paragraph. Example 2. Q is a local medical research organization... medical research of interest to Q. It receives support through small government grants and a few research... organization seeking section 509(a)(3) status, for the purpose of carrying on research and study projects...

  19. 26 CFR 1.509(a)-5 - Special rules of attribution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... described in subparagraph (1) of this paragraph. Example 2. Q is a local medical research organization... medical research of interest to Q. It receives support through small government grants and a few research... organization seeking section 509(a)(3) status, for the purpose of carrying on research and study projects...

  20. 26 CFR 1.509(a)-5 - Special rules of attribution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... described in subparagraph (1) of this paragraph. Example 2. Q is a local medical research organization... medical research of interest to Q. It receives support through small government grants and a few research... organization seeking section 509(a)(3) status, for the purpose of carrying on research and study projects...

  1. 26 CFR 1.509(a)-5 - Special rules of attribution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... described in subparagraph (1) of this paragraph. Example 2. Q is a local medical research organization... medical research of interest to Q. It receives support through small government grants and a few research... organization seeking section 509(a)(3) status, for the purpose of carrying on research and study projects...

  2. 26 CFR 1.509(a)-5 - Special rules of attribution.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... described in subparagraph (1) of this paragraph. Example 2. Q is a local medical research organization... medical research of interest to Q. It receives support through small government grants and a few research... organization seeking section 509(a)(3) status, for the purpose of carrying on research and study projects...

  3. Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4-naphthohydroquinone.

    PubMed

    Yuan, Xiu; Miller, Christopher J; Pham, A Ninh; Waite, T David

    2014-06-01

    Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH2Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5-7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH2Q increased with increasing pH and initial NH2Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ(2-), has been shown to be the reactive species with regard to the one-electron oxidation by O2 and comproportionation with the quinone species, both generating the semiquinone radical (NSQ(·-)). The oxidation of NSQ(·-) by O2 is shown to be the most important pathway for superoxide (O2(·-)) generation with a high intrinsic rate constant of 1.0×10(8)M(-1)s(-1). Both NSQ(·-) and O2(·-) served as chain-propagating species in the autoxidation of NH2Q. Cu(II) is capable of catalyzing the oxidation of NH2Q in the presence of O2 with the oxidation also accelerated by increasing the pH. Both the uncharged (NH2Q(0)) and the mono-anionic (NHQ(-)) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×10(4) and 1.2×10(7)M(-1)s(-1), respectively. The presence of O2 facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ(·-) resulting in the generation of O2(·-). The half-cell reduction potentials of various redox couples at neutral p

  4. LEOPARD-type SHP2 mutant Gln510Glu attenuates cardiomyocyte differentiation and promotes cardiac hypertrophy via dysregulation of Akt/GSK-3β/β-catenin signaling.

    PubMed

    Ishida, Hidekazu; Kogaki, Shigetoyo; Narita, Jun; Ichimori, Hiroaki; Nawa, Nobutoshi; Okada, Yoko; Takahashi, Kunihiko; Ozono, Keiichi

    2011-10-01

    LEOPARD syndrome (LS) is an autosomal dominant inherited multisystemic disorder. Most cases involve mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Src homology 2-containing protein phosphatase 2 (SHP2). LS frequently causes severe hypertrophic cardiomyopathy (HCM), even from the fetal period. However, the molecular pathogenesis has not been clearly elucidated. Here, we analyzed the roles of the LS-type SHP2 mutant Gln510Glu (Q510E), which showed the most severe type of HCM in LS, in cardiomyocyte differentiation, and in morphological changes. We generated mutant P19CL6 cell lines, the most convenient cardiomyocyte differentiation model, which continuously expressed SHP2-Q510E, SHP2-D61N (Noonan-type mutant), wild-type SHP2, and green fluorescent protein (native SHP2 expression only). SHP2-Q510E mutant P19CL6 cells showed significant attenuation of myofibrillogenesis, with increased proliferative activity. Mature cardiomyocytes from the SHP2-Q510E mutant were significantly larger than those of controls and the other mutants. However, expression of cardiac-specific transcriptional factors (Gata4, Tbx5, and Nkx2.5) did not differ significantly between the LS-type SHP2-Q510E mutants and the other mutants and controls. Our results indicate that SHP2-Q510E mutants can differentiate into cardiac progenitors but are inhibited from undergoing terminal differentiation into mature cardiomyocytes. In contrast, Akt and glycogen synthase kinase (GSK)-3β phosphorylation were upregulated, and nuclear β-catenin at the late stage of differentiation was highly accumulated in SHP2-Q510E mutant P19CL6 cells. Supplementation with the phosphoinositide 3-kinase/Akt inhibitor LY-294002 during the late stage of differentiation was found to partially restore myofibrillogenesis while suppressing the increase in size of individual mature cardiomyocytes derived from the SHP2-Q510E mutants. Our findings suggest that dysregulation of the Akt/GSK-3

  5. High-resolution solid-state NMR of quadrupolar nuclei

    PubMed Central

    Meadows, Michael D.; Smith, Karen A.; Kinsey, Robert A.; Rothgeb, T. Michael; Skarjune, Robert P.; Oldfield, Eric

    1982-01-01

    We report the observation of high-resolution solid-state NMR spectra of 23Na (I = [unk]), 27Al (I = [unk]) and 51V (I = [unk]) in various inorganic systems. We show that, contrary to popular belief, relatively high-resolution (≈10 ppm linewidth) spectra may be obtained from quadrupolar systems, in which electric quadrupole coupling constants (e2qQ/h) are in the range ≈1-5 MHz, by means of observation of the (½, -½) spin transition. The (½, -½) transition for all nonintegral spin quadrupolar nuclei (I = [unk], [unk], [unk], or [unk]) is only normally broadened by dipolar, chemical shift (or Knight shift) anisotropy or second-order quadrupolar effects, all of which are to a greater or lesser extent averaged under fast magic-angle sample rotation. In the case of 23Na and 27Al, high-resolution spectra of 23NaNO3 (e2qQ/h ≈300 kHz) and α-27Al2O3 (e2qQ/h ≈2-3 MHz) are presented; in the case of 51V2O5 (e2qQ/h ≈800 kHz), rotational echo decays are observed due to the presence of a ≈103-ppm chemical shift anisotropy. The observation of high-resolution solid-state spectra of systems having spins I = [unk], [unk], and [unk] in asymmetric environments opens up the possibility of examining about two out of three nuclei by solid-state NMR that were previously thought of as “inaccessible” due to the presence of large (a few megahertz) quadrupole coupling constants. Preliminary results for an I = [unk] system, 93Nb, having e2qQ/h ≈19.5 MHz, are also reported. PMID:16593165

  6. MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith–Magenis and fragile X syndromes

    PubMed Central

    Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

    2015-01-01

    Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith–Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders. PMID:25271084

  7. Low-power broadband homonuclear dipolar recoupling in MAS NMR by two-fold symmetry pulse schemes for magnetization transfers and double-quantum excitation

    NASA Astrophysics Data System (ADS)

    Teymoori, Gholamhasan; Pahari, Bholanath; Edén, Mattias

    2015-12-01

    We provide an experimental, numerical, and high-order average Hamiltonian evaluation of an open-ended series of homonuclear dipolar recoupling sequences, SR2 2p 1 with p = 1, 2, 3, … . While operating at a very low radio-frequency (rf) power, corresponding to a nutation frequency of 1/2 of the magic-angle spinning (MAS) rate (ωnut =ωr / 2), these recursively generated double-quantum (2Q) dipolar recoupling schemes offer a progressively improved compensation to resonance offsets and rf inhomogeneity for increasing pulse-sequence order p. The excellent recoupling robustness to these experimental obstacles, as well as to CSA, is demonstrated for 2Q filtering (2QF) experiments and for driving magnetization transfers in 2D NMR correlation spectroscopy, where the sequences may provide either double or zero quantum dipolar Hamiltonians during mixing. Experimental and numerical demonstrations, which mostly target conditions of "ultra-fast" MAS (≳50 kHz) and high magnetic fields, are provided for recoupling of 13C across a wide range of isotropic and anisotropic chemical shifts, as well as dipolar coupling constants, encompassing [2,3-13C2 ]alanine, [1,3-13C2 ]alanine, diammonium [1,4-13C2 ]fumarate, and [U-13 C]tyrosine. When compared at equal power levels, a superior performance is observed for the SR2p 1 sequences with p ⩾ 3 relative to existing and well-established 2Q recoupling techniques. At ultra-fast MAS, proton decoupling is redundant during the homonuclear dipolar recoupling of dilute spins in organic solids, which renders the family of SR2p 1 schemes the first efficient 2Q recoupling option for general applications, such as 2Q-1Q correlation NMR and high-order multiple-quantum excitation, under truly low-power rf conditions.

  8. Angelman syndrome in Denmark. birth incidence, genetic findings, and age at diagnosis.

    PubMed

    Mertz, Line Granild Bie; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Nielsen, Karen Brøndum; Grønskov, Karen; Østergaard, John R

    2013-09-01

    Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2-q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were to examine the birth incidence of AS in Denmark and to characterize the size of the 15q11.2-q13 deletions with 1,000K array CGH. In addition, we analyzed genotype differences in regard to age at diagnosis and investigated the occurrence of deletions/duplications outside the 15q11.2-q13 regions. We identified 51 patients with genetically verified AS, which corresponded to a birth incidence of 1:24,580 (95%CI: 1:23,727-1:25,433). Thirty-six patients showed a deletion; 13 had a Class I deletion and 20 had a Class II deletion. There was bimodal distribution of the BP3 breakpoint. Three patients had larger and atypical deletions, with distal breakpoints telomeric to BP3. Five patients had paternal uniparental disomy (pUPD) of chromosome 15, and four had a verified UBE3A mutation. Additional deletions/duplications outside the 15q11.2-q13 areas were demonstrated in half the participants. Six harbored more than one CNV. Mean age at diagnosis was 21 months (95%CI: 17-23 months) for children with a deletion and 46 months (95%CI: 36-55 months) for children with pUPD or a UBE3A mutation (P < 0.01). The presence of a CNV outside 15q11.2-q13 did not have an impact on age at diagnosis.

  9. Suppression of sodium nuclear magnetic resonance double-quantum coherence by chemical shift and relaxation reagents

    NASA Astrophysics Data System (ADS)

    Hutchison, Robert B.; Huntley, James J. A.; Jin, Haoran; Shapiro, Joseph I.

    1992-12-01

    An investigation into the signal suppression behavior of the paramagnetic shift and relaxation reagents, Dy(P3O10)27- and Gd(P3O10)27-, with regard to their use in the nuclear magnetic resonance spectroscopic study of sodium has been performed. Measurements of T1 and T2 relaxation time constants of sodium in normal saline, Krebs-Henseleit buffer, and human blood serum, as a function of concentration of these reagents showed that, although closely coupled in the saline and K-H buffer environments, in plasma T1 and T2 become decoupled, transverse relaxation dominating in comparison to longitudinal relaxation. Linewidth measurements further suggest that relaxation in the plasma milieu is controlled primarily by inherent T2 relaxation, rather than by field inhomogeneity or diffusion effects. Quantitative single-quantum (1Q) and double-quantum (2Q) intensity measurements, biexponential T2 relaxation measurements, and parametric studies of the preparation time of the 2Q pulse sequence, were obtained in suspensions of bovine serum albumin and human erythrocytes. The observed suppression of sodium 2Q coherence by paramagnetic shift and relaxation reagents was found to exhibit a complex behavior in albumin solutions, involving the biexponential T2 decay to be expected during the preparation time of the 2Q filter pulse sequence, as well as the optimum preparation time for production of the double-quantum coherence itself. The controlling factor for both of these effects is the biexponential amplitude function in the expression for the transverse magnetization observed following application of the 2Q pulse sequence. This in turn is determined entirely by the values for the slow and fast components of biexponential relaxation in sodium, which themselves depend upon the concentration of the macromolecular binding sites for quadrupolar interaction. A similar behavior has been observed in suspensions of human erythrocytes.

  10. Low-power broadband homonuclear dipolar recoupling in MAS NMR by two-fold symmetry pulse schemes for magnetization transfers and double-quantum excitation.

    PubMed

    Teymoori, Gholamhasan; Pahari, Bholanath; Edén, Mattias

    2015-12-01

    We provide an experimental, numerical, and high-order average Hamiltonian evaluation of an open-ended series of homonuclear dipolar recoupling sequences, SR [Formula: see text] with p=1,2,3,…. While operating at a very low radio-frequency (rf) power, corresponding to a nutation frequency of 1/2 of the magic-angle spinning (MAS) rate (ωnut=ωr/2), these recursively generated double-quantum (2Q) dipolar recoupling schemes offer a progressively improved compensation to resonance offsets and rf inhomogeneity for increasing pulse-sequence order p. The excellent recoupling robustness to these experimental obstacles, as well as to CSA, is demonstrated for 2Q filtering (2QF) experiments and for driving magnetization transfers in 2D NMR correlation spectroscopy, where the sequences may provide either double or zero quantum dipolar Hamiltonians during mixing. Experimental and numerical demonstrations, which mostly target conditions of "ultra-fast" MAS (≳50kHz) and high magnetic fields, are provided for recoupling of (13)C across a wide range of isotropic and anisotropic chemical shifts, as well as dipolar coupling constants, encompassing [2,3-(13)C2]alanine, [1,3-(13)C2]alanine, diammonium [1,4-(13)C2]fumarate, and [U-(13)C]tyrosine. When compared at equal power levels, a superior performance is observed for the SR [Formula: see text] sequences with p⩾3 relative to existing and well-established 2Q recoupling techniques. At ultra-fast MAS, proton decoupling is redundant during the homonuclear dipolar recoupling of dilute spins in organic solids, which renders the family of SR [Formula: see text] schemes the first efficient 2Q recoupling option for general applications, such as 2Q-1Q correlation NMR and high-order multiple-quantum excitation, under truly low-power rf conditions.

  11. MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.

    PubMed

    Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

    2015-06-01

    Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders.

  12. Three novel polymorphic microsatellite markers for the glaucoma locus GLC1B by datamining tetranucleotide repeats on chromosome 2p12-q12

    PubMed Central

    2009-01-01

    In order to identify new markers around the glaucoma locus GLC1B as a tool to refine its critical region at 2p11.2-2q11.2, we searched the critical region sequence obtained from the UCSC database for tetranucleotide (GATA)n and (GTCT)n repeats of at least 10 units in length. Three out of four potential microsatellite loci were found to be polymorphic, heterozygosity ranging from 64.56% to 79.59%. The identified markers are useful not only for GLC1B locus but also for the study of other disease loci at 2p11.2-2q11.2, a region with scarcity of microsatellite markers. PMID:21637444

  13. The Role of MicroRNAs in Human Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    mir -455 9q33.2-q34.3 124.017-140.242 9.8 (1) 0.0066 271,8,65 - hsa- mir -600,hsa- mir -601,hsa- mir - 181a-2,hsa- mir - 181b -2,hsa- mir - 199b,hsa- mir -219- 2...e.g., our recent results on mir -143 as a determinant of aggressive liposarcoma, our work and Sam Singer, private communication). We are currently...Genetic element of interest microRNAs 1q21.2-q21.3 148.035-151.149 8.2 (1.5) 0.0124 101,1,37 MCL1,ARNT hsa- mir -554 1q21.3-q22 151.576-153.639 8.2 (1.5

  14. Mesoscopic Study of a Square Cavity Ventilated and heated by the bottom

    NASA Astrophysics Data System (ADS)

    Bouayed, Z. E.; Houat, S.

    2017-03-01

    In this paper, we present a numerical study of the laminar mixed convection in a ventilated cavity square; one of the walls is subjected to a constant temperature, while the other walls are considered adiabatic. The thermal lattice Boltzmann method with the double population model was used. A computer code was developed with the D2Q9 model for the velocity field and D2Q5 for the temperature field to determine the whole structure of the flow. The results are presented in the form of thermal fields for the Richardson number Ri = 10. Those show that each time the Richardson number increases, the number of Nusselt increases too what justifies an increase in the heat transfer.

  15. Optical Excitations and Energy Transfer in Nanoparticle Waveguides

    DTIC Science & Technology

    2009-03-01

    OffDiag_int_B(2*q*R*sin(ii*%pi/N), %pi/2, 0, m, n, mu, nu); end y=Summ; endfunction function y= Miel (n, z, n_r) //Mie scattering coefficient for...0.0000000001; q=q_0; n=l; mm=N/2; disp("lst transverse mode tl"); delt=l; k=0; while abs(delt/q) > hA(3/2) k=k+l; denomin=l/ Miel (l, q, n_r...2, 0, n, 0, n, N)- 4*OffDiag_int_B_Four_xy_sph(mm-l/2, q, 2, 0, 1, 1, 1, N)A2/denomin ; denominh=l/ Miel (l, q+h, n_r)+Diag_int_A_Four_xy_sph(mm-l, q

  16. Angular Rate Estimation for Multi-Body Spacecraft Attitude Control

    DTIC Science & Technology

    2001-06-01

    q2oi,q3oi,sqrt(1-q1oi^2-q2oi^2-q3oi^2)]; %Initial body with respect to inertial direction cosine matrix dcmi (1,1)=qi(1)^2-qi(2)^2-qi(3)^2+qi(4)^2... dcmi (1,2)=2*(qi(1)*qi(2)+qi(3)*qi(4)); dcmi (1,3)=2*(qi(1)*qi(3)-qi(2)*qi(4)); dcmi (2,1)=2*(qi(1)*qi(2)-qi(3)*qi(4)); dcmi (2,2)=-qi(1)^2+qi(2)^2...qi(3)^2+qi(4)^2; dcmi (2,3)=2*(qi(2)*qi(3)+qi(1)*qi(4)); dcmi (3,1)=2*(qi(1)*qi(3)+qi(2)*qi(4)); dcmi (3,2)=2*(qi(2)*qi(3)-qi(1)*qi(4)); dcmi (3,3)=-qi

  17. The Color Dipole Picture and the Ratio of the Longitudinal to the Transverse Photoabsorption Cross Section

    SciTech Connect

    Schildknecht, Dieter

    2009-03-23

    The transverse size of qq-bar fluctuations of a longitudinally polarized photon is reduced relative to the transverse size of qq-bar fluctuations of a transversely polarized photon. This implies a model-independent prediction of the ratio R(W{sup 2},Q{sup 2}){identical_to}{sigma}{sub L}/{sigma}{sub T} = 0.375, or, equivalently, F{sub L}/F{sub 2} = 0.27, for x congruent with Q{sup 2}/W{sup 2}<<1 and Q{sup 2} sufficiently large, while R(W{sup 2},Q{sup 2}) 0.50, if this effect is ignored. Experimental data from HERA confirm the transverse-size reduction.

  18. APPLICATION OF 129I MOSSBAUER EFFECT TO BIOLOGICAL SYSTEMS: STUDIES WITH HEME MODELS*

    PubMed Central

    Pasternak, M.; Debrunner, Peter G.; DePasquali, G.; Hager, Lowell P.; Yeoman, L.

    1970-01-01

    The Mossbauer effect associated with 129I, 125Te, and 57Fe has been applied to investigate structural properties of the axial ligands in ferric-high spin hematoheme-I, hematoheme-Te, and hematoheme-histidine-iodide. The magnitude and sign of the 129I quadrupole coupling constant (e2qQ) and the isomer shift, as deduced from the Mossbauer effect spectra, are consistent with an axial, s-p hybridized bond of overwhelming σ-character. Identical coupling constant (e2qQ(127I) = -1826 ± 3 MHz) were measured for both heme-I and hematoheme-histidine-iodide. Implications of this result to the nature of ferric-high spin heme-histidine complexing are discussed. A stable heme 125Te species formed in the electron-capture decay of heme-125I is observed, and structural properties of this singly bonded telluride ligand are discussed. PMID:16591848

  19. The spectrum of comet C/2009 R1 (McNaught) in 4140-5240 Å wavelength region

    NASA Astrophysics Data System (ADS)

    Korsun, Pavlo; Kulyk, Irina; Velichko, Sergey

    2012-01-01

    The spectroscopic observations of comet C/2009 R1 (McNaught) were carried out with the 2 m Zeiss-RCC Telescope of Pik Terskol Observatory operated by the International Center for Astronomical and Medico-Ecological Research (Ukraine, Russia). The Multi Mode Cassegrain spectrometer was used to obtain spectra of moderate spectral resolving power with a wavelength coverage from 4140 to 5240 Å. The spectrum is characterized by the extremely low continuum level and strong molecular features. 192 emission lines of C2, CN, CH, NH2, CO+, and CH+ have been identified by the comparison of the observed and theoretical spectra of the molecules. The ratios of the gas production rates of Q(C2)/Q(CN)=1.32, Q(CH)/Q(CN)=0.49, and Q(NH2)/Q(CN)=0.81 were derived using a Haser model.

  20. On the cubic velocity deviations in lattice Boltzmann methods

    NASA Astrophysics Data System (ADS)

    Házi, Gábor; Kávrán, Péter

    2006-03-01

    The macroscopic equations derived from the lattice Boltzmann equation are not exactly the Navier-Stokes equations. Here the cubic deviation terms and the methods proposed to eliminate them are studied. The most popular two- and three-dimensional models (D2Q9, D3Q15, D3Q19, D3Q27) are considered in the paper. It is demonstrated that the compensation methods provide only partial elimination of the deviations for these models. It is also shown that the compensation of Qian and Zhou (1998 Europhys. Lett. 42 359) using the compensation parameter K = 1 in a D2Q9 or D3Q27 model can eliminate all the cross terms perfectly, but the deviation terms ∂xρu3x, ∂yρu3y and ∂zρu3z still survive the compensation.

  1. Multiscale Talbot effects in Fibonacci geometry

    NASA Astrophysics Data System (ADS)

    Ho, I.-Lin; Chang, Yia-Chung

    2015-04-01

    This article investigates the Talbot effects in Fibonacci geometry by introducing the cut-and-projection construction, which allows for capturing the entire infinite Fibonacci structure in a single computational cell. Theoretical and numerical calculations demonstrate the Talbot foci of Fibonacci geometry at distances that are multiples (τ +2){{({{F}μ }+τ {{F}μ +1})}-1}p/(2q) or (τ +2){{({{L}μ }+τ {{L}μ +1})}-1}p/(2q) of the Talbot distance. Here (p, q) are coprime integers, μ is an integer, τ is the golden mean, and {{F}μ } and {{L}μ } are Fibonacci and Lucas numbers, respectively. The image of a single Talbot focus exhibits a multiscale-interval pattern due to the self-similarity of the scaling Fourier spectrum.

  2. Redundancies and Don’t Cares in Sequential Logic Synthesis

    DTIC Science & Technology

    1989-05-01

    relation 2 sa1 sa3 INT2 INT2 qbl qb3 ot2 q - q2, with similar compatibility relations q2 -q and il sa2 sal INT2 INT1 qb2 qb2 out3 q - s. However, the three...intersection, implying that qi, and qsa ii sa3 sal INTl INT1 qb3 qb2 out4 not be merged into a single state, even thou allthe req e pairwise compatibility...relations exist. In the binary-valuedi2 sa3 sa2 INT1 INT2 qb3 qb3 out1 output case,ifte possible output combinations can be repre- sented as a single cube

  3. Low-power broadband homonuclear dipolar recoupling without decoupling: Double-quantum 13C NMR correlations at very fast magic-angle spinning

    NASA Astrophysics Data System (ADS)

    Teymoori, Gholamhasan; Pahari, Bholanath; Stevensson, Baltzar; Edén, Mattias

    2012-09-01

    We report novel symmetry-based radio-frequency (rf) pulse sequences for efficient excitation of double-quantum (2Q) coherences under very fast (>60 kHz) magic-angle spinning (MAS) conditions. The recursively generated pulse-scheme series, R22p1R22p-1(p=1,2,3,…), offers broadband 13C-13C recoupling in organic solids at a very low rf power. No proton decoupling is required. A high-order average Hamiltonian theory analysis reveals a progressively enhanced resonance-offset compensation for increasing p, as verified both by numerical simulations and 2Q filtration NMR experiments on 13C2-glycine, [2,3-13C2]alanine, and [U-13C]tyrosine at 14.1 T and 66 kHz MAS, where the pulse schemes with p⩾3 compare favorably to current state-of-the-art recoupling options.

  4. Quadratic Herman-Wallis factors in the fundamental bands of linear molecules

    NASA Astrophysics Data System (ADS)

    Watson, James K. G.

    1987-10-01

    General theoretical formulas are derived for the coefficients in the terms M˜12 and M˜13 of the effective molecular dipole moment operator, and applied to the parallel and perpendicular fundamentals of linear molecules. The Herman-Wallis factors for P- and R-branch lines are F PR = [1 + A 1m + A 2PRm 2] 2, m = δ J( J' + J″ + 1)/2 and for Q-branch lines F Q = [1 + A 2QJ ( J + 1)] 2 The quadratic coefficients A2PR and A2Q depend on up to cubic potential derivatives and quadratic dipole derivatives. Calculated A2PR and A2Q values for the fundamentals of CO 2 do not agree well with recent measurements of Johns, and possible reasons for the discrepancies are discussed.

  5. Three novel polymorphic microsatellite markers for the glaucoma locus GLC1B by datamining tetranucleotide repeats on chromosome 2p12-q12.

    PubMed

    Murga-Zamalloa, Carlos; Guevara-Fujita, Maria Luisa; Estrada-Cuzcano, Alejandro; Fujita, Ricardo

    2009-10-01

    In order to identify new markers around the glaucoma locus GLC1B as a tool to refine its critical region at 2p11.2-2q11.2, we searched the critical region sequence obtained from the UCSC database for tetranucleotide (GATA)n and (GTCT)n repeats of at least 10 units in length. Three out of four potential microsatellite loci were found to be polymorphic, heterozygosity ranging from 64.56% to 79.59%. The identified markers are useful not only for GLC1B locus but also for the study of other disease loci at 2p11.2-2q11.2, a region with scarcity of microsatellite markers.

  6. A Model of Direct Gauge Mediation of Supersymmetry Breaking

    NASA Astrophysics Data System (ADS)

    Murayama, Hitoshi

    1997-07-01

    We present the first phenomenologically viable model of gauge meditation of supersymmetry breaking without a messenger sector or gauge singlet fields. The standard model gauge groups couple directly to the sector which breaks supersymmetry dynamically. Despite the direct coupling, it can preserve perturbative gauge unification thanks to the inverted hierarchy mechanism. There is no dangerous negative contribution to m2q~, m2l~ due to two-loop renormalization group equation. The potentially nonuniversal supergravity contribution to m2q~ and m2l~ can be suppressed enough. The model is completely chiral, and one does not need to forbid mass terms for the messenger fields by hand. Cosmology of the model is briefly discussed.

  7. Form of 15q proximal duplication appears to be a normal euchromatic variant

    SciTech Connect

    Jalal, S.M.; Persons, D.L.; DeWald, G.W.; Lindor, N.M.

    1994-10-01

    Deletions involving often leads to either Prader-Willi or Angelman syndrome, depending on the hereditary path of the deletion (paternal or maternal). A number of cases have been reported in which duplications involving 15q11.2-q13 have not been associated with any detectable phenotypic abnormalities. Ludowese et al. (1991) have summarized 25 such cases that include 10 of their own cases from 5 unrelated families. They conclude that duplication of 15q12-13 does not have an adverse phenotypic effect, though they do not completely rule out the possibility that, instead of 15q12-13 duplication, the extra material could be an insertion from another chromosome. Thus, the dilemma is when duplication of 15q11.2-q13 is clinically significant. We suggest that certain kinds of amplification or duplication involving distal 15q12 and 15q13 may represent a normal variant. 14 refs., 1 fig., 1 tab.

  8. Array CGH characterization of an unbalanced X-autosome translocation associated with Xq27.2-qter deletion, 11q24.3-qter duplication and Xq22.3-q27.1 duplication in a girl with primary amenorrhea and mental retardation.

    PubMed

    Chen, Chih-Ping; Lin, Shuan-Pei; Chern, Schu-Rern; Kuo, Yu-Ling; Wu, Peih-Shan; Chen, Yu-Ting; Lee, Meng-Shan; Wang, Wayseen

    2014-02-01

    We present array comparative genomic hybridization (aCGH) characterization of an unbalanced X-autosome translocation with an Xq interstitial segmental duplication in a 16-year-old girl with primary ovarian failure, mental retardation, attention deficit disorder, learning difficulty and facial dysmorphism. aCGH analysis revealed an Xq27.2-q28 deletion, an 11q24.3-q25 duplication, and an inverted duplication of Xq22.3-q27.1. The karyotype was 46,X,der(X)t(X;11)(q27.2;q24.3) dup(X)(q27.1q22.3). We discuss the genotype-phenotype correlation in this case. Our case provides evidence for an association of primary amenorrhea and mental retardation with concomitant unbalanced X-autosome translocation and X chromosome rearrangement.

  9. First Principles Study of Nuclear Quadrupole Interactions in Single and Double Chain DNA and Solid Nucleobases

    NASA Astrophysics Data System (ADS)

    Das, T. P.; Pink, R. H.; Badu, S. R.; Dubey, Archana; Scheicher, R. H.; Saha, H. P.; Chow, Lee; Huang, M. B.

    2009-03-01

    Nuclear Quadrupole Interactions (NQI) of ^17O, ^14N and ^2H nuclei have been studied for free nucleobases and nucleobases in single strand and double strand DNA and in solid state. Our first-principles investigations were carried out using the Gaussian 2003 set of programs to implement the Hartree-Fock procedure combined with many-body effects included using many-body perturbation theory. As expected for NQI in general, many-body effects are found to be small. Results will be presented for the quadrupole coupling constants (e^2qQ) and asymmetry parameters (η) for the nucleobases in the various environments. Trends in e^2qQ and η in the different environments will be discussed. In the case of the solid nucleobases, comparisons will be made with available experimental data [1] for ^17O nuclei.[3pt] [1] Gang Wu et al., J. Am. Chem. Soc. 124, 1768 (2002)

  10. Economic Feasibility of DLA (Defense Logistics Agency) Materiel Maintenance Mission

    DTIC Science & Technology

    1988-10-01

    Costs Indirect Labor 185 192 191 191 759 Overhead 515 515 515 515 2060 Depreciation 80 80 80 80 320 Admin. Costs 34 37 35 35 141 Total Fixed Costs 814...4Q86 1Q87 2Q87 3Q87 4Q87 Depreciation 80 80 80 80 80 80 except as noted, itt figures in thousands e.7 Stock Maintenance Dtyision Defense Depot O&den

  11. Two-photon exchange corrections to the pion form factor

    DOE PAGES

    Peter G. Blunden; Melnitchouk, Wally; Tjon, John A.

    2010-01-06

    Here, we compute two-photon exchange corrections to the electromagnetic form factor of the pion, taking into account the finite size of the pion. Compared to the soft-photon approximation for the infrared divergent contribution which neglects hadron structure effects, the corrections are found to be ≲ 1% for small Q2 (Q2 < 0.1 GeV2), but increase to several percent for Q2 ≳ 1 GeV2 at extreme backward angles.

  12. International Symposium on Epidemic Hemorrhagic Fever (Hemorrhagic Fever with Renal Syndrome) Held in Wuhan, Hubei, China on 31 October - 2 November 1988

    DTIC Science & Technology

    1989-10-01

    Effect of Type I Allergy on the Pathogenesis of likso Rill CLINICAL MANAGEMENT OF HERS CHAIRMENsT.M. COSGRIFF, Wut 2q00 Yang W.S. A Double Blind Study...through the whole year, the highest rate was in September to November and its seasonal fluctuation was conformable to the incidence of humen EHF cases...populations. The prevalence of antibody positive bank voles shows considerable seasonal variation. The pattern of seasonal va- riation is different when

  13. Genetic and Physiological Control of Protective Antigen Synthesis by Bacillus Anthracis

    DTIC Science & Technology

    1981-12-01

    Unclassified AD REPORT NUMBER TWO GENETIC AND PHYSIOLOGICAL CONTROL OF PROTECTIVE ANTIGEN SYNTHESIS BY BACILLUS ANTHRACIS ANNUAL PROGRESS REPORT...Physiological Control of Protective Annual Report Antigen Synthesis by Bacillus anthracis Jan. 1, 1981 - Dec. 31,198 6. PERFORMING ORG. REPORT NUMBER...neceteemy mid Identify by block number) Bacillus anthracis Anthrax protective antigen Anthrax toxin 2Q. ASSMI*ACT (Camnot en r everit stO neneesemy md fd

  14. Invariants of Boundary Link Cobordism

    NASA Astrophysics Data System (ADS)

    Sheiham, Desmond

    2001-10-01

    An n-dimensional μ-component boundary link is a codimension 2 embedding of spheres L=bigsqcup_{μ}S^n subset S^{n+2} such that there exist μ disjoint oriented embedded (n+1)-manifolds which span the components of L. An F_μ-link is a boundary link together with a cobordism class of such spanning manifolds. The F_μ-link cobordism group C_n(F_μ) is known to be trivial when n is even but not finitely generated when n is odd. Our main result is an algorithm to decide whether two odd-dimensional F_μ-links represent the same cobordism class in C_{2q-1}(F_μ) assuming q>1. We proceed to compute the isomorphism class of C_{2q-1}(F_μ), generalizing Levine's computation of the knot cobordism group C_{2q-1}(F_1). Our starting point is the algebraic formulation of Levine, Ko and Mio who identify C_{2q-1}(F_μ) with a surgery obstruction group, the Witt group G^{(-1)^q,μ}(Z) of μ-component Seifert matrices. We obtain a complete set of torsion-free invariants by passing from integer coefficients to complex coefficients and by applying the algebraic machinery of Quebbemann, Scharlau and Schulte. Signatures correspond to `algebraically integral' simple self-dual representations of a certain quiver (directed graph with loops). These representations, in turn, correspond to algebraic integers on an infinite disjoint union of real affine varieties. To distinguish torsion classes, we consider rational coefficients in place of complex coefficients, expressing G^{(-1)^q,μ}(Q) as an infinite direct sum of Witt groups of finite-dimensional division Q-algebras with involution. Numerical invariants of such Witt groups are available in the literature.

  15. Comparison of Sonar Discrimination by an Echolocating Dolphin and a Counterpropagation Neural Network

    DTIC Science & Technology

    1992-09-01

    AND SUBTITLE 5 FUNDING NUMBERS COMPARISON OF SONAR DISCRIMINATION BY AN ECHOLOCATING PR: MMB2 DOLPHIN AND A COUNTERPROPAGATION NEURAL NETWORK PE...COMPARISON OF SONAR DISCRIMINATION BY AN constanB-1 filter cal fe expressed as ECIHOLOCATING DOLPHIN AND A COUNTERPROPAGATION 2Q-1 NEURAL NETWORK ’ " -- 1...In this study, a counterpropagation artificial layer of N+1 elements, a Kohonen layer of N elements neural network was used to examine the broadband

  16. National Dam Safety Program. West Millpond Dam (NY 01060), Mohawk River Basin, City of Gloversville, Fulton County, New York. Phase I Inspection Report,

    DTIC Science & Technology

    1981-09-02

    KNowN, 8) Data on Electrical & Mechanical Equipment Affecting Safe Operation of Dam Not.Kjp jtJ j,. 9) Other, OIL F2-2 t 4576 b. Modifications (review...ny~RERS OF_- _ :~iI 0LMOT BUCK CLOVES AND MIuTE ~~" ~Gloversville, N...2Q .... 19. TeCon-2crn-ton Commizosion, RECEIVED Albany, It .SEP 16 1913 Cc

  17. Industrial Hygiene Special Study Number 55-66-0216-81 N-Nitrosodimethylamine, Hydrazine, and 1-1-Dimethylhydrazine Exposures at the Hydrazine Blending Facility, Rocky Mountain Arsenal, Commerce City, CO

    DTIC Science & Technology

    1980-10-28

    toxicity and presumed zarzinoge.aic potential of N-Nitrosodimethylamine, contact should not be permitted by any route." (b) OSHA Standard 2q CFR 1910.ll06...Even though the sump is now being precharged with calcium hypochlorite to oxidize the hydrazines, and a floating plastic cover has been added to reduce ...references 14 & 15). 8. RECOMMENDATIONS. a. The following recommendations are made for reducing the number of sources of exposures at the hydrazine

  18. Gene Fusion Analysis of Positive Charge-Induced Segment Re-orientation in the Tetracycline Resistance Protein

    DTIC Science & Technology

    1993-02-01

    indicated by hydrolysis of p- nitrophenyl phosphate and is measured at A.2Q- Turbidity is corrected by measuring the optical density at Asso and using... nitrophenyl phosphate hydrolysis assay (Table II). The 10 mutation conferred a 3.5-fold increase in Miller Unit activity compared to the wild-type...Nevertheless, the p- nitrophenyl phosphate assay demonstrates that the alkaline phosphatase domain is exported to the periplasm, whereas the wild-type TetS-AP

  19. National Dam Safety Program. Longstreet Lake Dam (MO 30832), Missouri - Kansas City Basin, Warren County, Missouri. Phase I Inspection Report.

    DTIC Science & Technology

    1980-09-01

    elevrtions to determine the discharge rating curve for the drop inlet spillway. 3. The emergency spillway section consists of a broad - crested , trapezoidal...was considered negligible. Tie following equ:ation was used for crest control: 3/2 Q = C (2 R HO s where "C " is a coefficient obtained from Figure...Brater, pages 8-5 and 8-6. Discharge quantities, determined by the methods described herein were plotted versus corresponding lake water surface

  20. Studies on Radar and Non-radar Sensor Networks

    DTIC Science & Technology

    2006-06-15

    selection based on specific applications. References [1] Q . Liang, "Waveform Design and Diversity in Radar Sensor Networks: Theoretical Analysis and...Application to Automatic Target Recognition," submitted to IEEE Trans on Aerospace and Electronic Systems. [2] Q . Liang, "Waveform Design and Diversity in...Sensor Networks, June 2006, New York. [3] Q . Liang, "Radar Sensor Networks: Algorithms for Waveform Design and Diversity with Appli- cation to ATR with

  1. The Impact of Cohesion on Platoon Performance at the Joint Readiness Training Center

    DTIC Science & Technology

    1988-10-01

    Army Project Number Manpower and Personnel 2Q263731A792 Approved for public release: distribution unlimited. iii FOREWORD A primary mission of the...in the platoon. DISCUSSION T. It is an understatement to say that it is difficult to measure the wholistic performance of an infantry platoon on a 12...JRTC. THE IMPACT OF COHESION. The primary purpose of this report was to describe the relationship between the home station measures of cohesion on 9

  2. The Clemson University, University Research Initiative Program in Discrete Mathematics and Computational Analysis

    DTIC Science & Technology

    1990-03-01

    Final Report D T IC The Clemson University A LECTE University Research Initiative Program APR 0 2 1990 in Discrete Mathematics & D Computational...Analsis AIOOlVI-2-- q3 March 1990 - Clemson University created in September 1986 a University Research Initiative Program in Discrete Mathematics and...year the Steering Committee selected outstanding visiting faculty who were supported by funds supplied by Clemson University with reduced teaching

  3. Nanophase and Nanocomposite Materials II. Symposium Held December 2-5, 1996, Boston, Massachusetts, U.S.A. Volume 457.

    DTIC Science & Technology

    1996-12-01

    ZIRCONIA NANOPHASES BOKHMI*, A. MORALES*, 0. NOVARO*, M. PORTILLA **, T. LOPEZ***, F. TZOMPANTZI***, R. GOMEZ*** *Institute of Physics, UNAM, A. P. 20...813. (30) International Tables for X-ray Crystallography; The Kynoch Press: Birmingham, UK, 1968; Vol. 3. (31) Miguel , J. J. d.; Cebollada, A...M. Janicke, B. F. Chmelka, Science 261, 1299 (1993). 2Q. Huo, D. I. Margolese, U. Ciesla, P. Feng, T. E. Gier, P. Sieger, R. Leon , P. M. Petroff, F

  4. A Test Fixture for Simulating Human Limb Physiology and Soft Tissue Biomechanics

    DTIC Science & Technology

    1989-04-14

    int, int); vodse p~rocess-di sp(vcd)3void d,-cwLoop-outline(void); "T~ eor disclosure of report data is subject to the restriction on the Title 27...setstclr( &briQ• htgr •, &bright green); s1:ext• ecstbL ); setstctr( &li3•_blue, &kigh•, blue ); i det [cur,’); ) el,•e if (gl grlh• == 2 !! Q1_gr• == 3) ( l•s

  5. Modeling HIV Immune Response and Validation with Clinical Data

    DTIC Science & Technology

    2007-03-28

    Harvard Medical School I.D. Unit–Gray 5 Boston, MA 02114 March 28, 2007 Abstract A system of ordinary differential equations is formulated to describe the...2 + 1 σ̂22 Nj2∑ i=1 |yij2 − z2(tij2 ; q)|2   σ̂2k = 1 N jk Njk∑ i=1 |yijk − zk (tijk ; q̂j)|2, k = 1, 2, (5.1) for the log10-transformed system of

  6. Down syndrome due to a recombination of a chromosome 21 paracentric inversion in 1 of 2 cases with a review of paracentric recombinants

    SciTech Connect

    Jewett, T.; Rao, P.N.; Berry, M.

    1994-09-01

    We recently identified 2 paracentric inversions (PAI) of chromosome 21. Case 1 was identified prenatally and paternally inherited: 46,XY,inv(21)(q21.2q22.13). The outcome is pending. Case 2 was a newborn male infant with clinical features of Down syndrome and an apparent inversion-duplication within chromosome 21. Parental chromosome analysis showed a maternal PAI: 46,XX,inv(21)(q21.2q22.3). The resulting child`s karyotype was: 46,XY,rec(21)(pter{yields}q21.2::q22.3{yields}q21.2::q22.3{yields}pter). Duplication of chromosome region q22.3{yields}qter was confirmed by FISH using a Down syndrome region specific probe (Cambio). Cytologically, the cornerstone of meiotic recombination from a paracentric inversion is the {open_quotes}reverse loop{close_quotes} model. In this model, a crossover event in the inversion loop results in the formation of gametes carrying either a dicentric chromatid, an acentric fragment, a normal chromatid or a chromatid with an inversion. However, a literature review of 326 PAI identified only 2 dicentrics and 15 other recombinants: 1 duplication/deletion; 6 deletions; 8 duplications. A U-type exchange model during meiosis within the inversion loop may best account for duplication/deletion recombinants. In contrast, the recombination in our case 2 would have occurred outside the loop. It is possible that no single explanation for PAI recombination may account for all outcomes. Alternative models of PAI recominational events will be presented. The literature suggests a low risk for prenatal loss due to abnormal PAI recombinants. In our review, viable offspring with recombinant chromosomes occurred in 3.8% of the PAI. Considering the potential for an increased incidence of recombination, prenatal diagnosis for all PAI carriers is warranted.

  7. Toxicological Evaluation of Pyrethroid Insecticide (5-Benzyl-3-Furyl) Methyl-2,2-Dimethyl-3-(2-methylpropenyl) Cyclopropanecarboxylate (Resmethrin)

    DTIC Science & Technology

    1977-05-16

    administration clinical chemistry tests tA Unclassified 66CUmITY CLASIIFICATION OF THIS PAOltWhee Da te Ento,,d...P-2 Q - Tabl4 1. 90-Day Feeding Study - Summary of Clinical Chemistry Results - Female Rats...Q-1 Table 2. 90-Day Feeding Studu’ - summary of Clinical Chemistry Resulte - Male Rate . Q-2 R - 21-Day Intravenous Study Summary of Orgazi-To

  8. Cell class-specific regulation of neocortical dendrite and spine growth by AMPA receptor splice and editing variants.

    PubMed

    Hamad, Mohammad I K; Ma-Högemeier, Zhan-Lu; Riedel, Christian; Conrads, Claudius; Veitinger, Thomas; Habijan, Tim; Schulz, Jan-Niklas; Krause, Martin; Wirth, Marcus J; Hollmann, Michael; Wahle, Petra

    2011-10-01

    Glutamatergic transmission converging on calcium signaling plays a key role in dendritic differentiation. In early development, AMPA receptor (AMPAR) transcripts are extensively spliced and edited to generate subunits that differ in their biophysical properties. Whether these subunits have specific roles in the context of structural differentiation is unclear. We have investigated the role of nine GluA variants and revealed a correlation between the expression of flip variants and the period of major dendritic growth. In interneurons, only GluA1(Q)-flip increased dendritic length and branching. In pyramidal cells, GluA2(Q)-flop, GluA2(Q)-flip, GluA3(Q)-flip and calcium-impermeable GluA2(R)-flip promoted dendritic growth, suggesting that flip variants with slower desensitization kinetics are more important than receptors with elevated calcium permeability. Imaging revealed significantly higher calcium signals in pyramidal cells transfected with GluA2(R)-flip as compared with GluA2(R)-flop, suggesting a contribution of voltage-activated calcium channels. Indeed, dendritic growth induced by GluA2(R)-flip in pyramidal cells was prevented by blocking NMDA receptors (NMDARs) or voltage-gated calcium channels (VGCCs), suggesting that they act downstream of AMPARs. Intriguingly, the action of GluA1(Q)-flip in interneurons was also dependent on NMDARs and VGCCs. Cell class-specific effects were not observed for spine formation, as GluA2(Q)-flip and GluA2(Q)-flop increased spine density in pyramidal cells as well as in interneurons. The results suggest that AMPAR variants expressed early in development are important determinants for activity-dependent dendritic growth in a cell type-specific and cell compartment-specific manner.

  9. Design of Tunable, Thin, and Wide-band Microwave Absorbers

    DTIC Science & Technology

    2012-04-05

    switchable or tunable radar absorbers, which are very useful in electromagnetic compatibility test facilities, radar camouflage and deception roles, and...applications requires switchable or tunable radar absorbers, which are very useful in electromagnetic compatibility test facilities, radar camouflage ...2012. [2] Q. Zhang and Z. Shen, “A dual-polarized switchable microwave absorber,” IEEE AP- S International Symposium , Chicago, July 2012.

  10. Dressed skeleton expansion and the coupling scale ambiguity problem

    SciTech Connect

    Lu, Hung Jung

    1992-09-01

    Perturbative expansions in quantum field theories are usually expressed in powers of a coupling constant. In principle, the infinite sum of the expansion series is independent of the renormalization scale of the coupling constant. In practice, there is a remnant dependence of the truncated series on the renormalization scale. This scale ambiguity can severely restrict the predictive power of theoretical calculations. The dressed skeleton expansion is developed as a calculational method which avoids the coupling scale ambiguity problem. In this method, physical quantities are expressed as functional expansions in terms of a coupling vertex function. The arguments of the vertex function are given by the physical momenta of each process. These physical momenta effectively replace the unspecified renormalization scale and eliminate the ambiguity problem. This method is applied to various field theoretical models and its main features and limitations are explored. For quantum chromodynamics, an expression for the running coupling constant of the three-gluon vertex is obtained. The effective coupling scale of this vertex is shown to be essentially given by {mu}{sup 2} {approximately} Q{sub min}{sup 2}Q{sub med}{sup 2}/Q{sub max}{sup 2} where Q{sub min}{sup 2}Q{sub med}{sup 2}/Q{sub max}{sup 2} are respectively the smallest, the next-to-smallest and the largest scale among the three gluon virtualities. This functional form suggests that the three-gluon vertex becomes non-perturbative at asymmetric momentum configurations. Implications for four-jet physics is discussed.

  11. Improved Tactical Engagement Simulation Training Techniques: Two Training Programs for the Conduct of After Action Reviews

    DTIC Science & Technology

    1979-01-01

    the skills required for accurate reconstruction of exercise events and the management of the exercise partici- pants to produce the most effective le...Project 2Q763743A773 and the TRADOC System Manager for Tactical Engagement Simulation of the US Army Training Support Center, Fort Eustis, Virginia. ~JO...SAsking open-ended questions. e Maintaining a low profile. * Managing a learning group. * Summarizing. You probably have most of these skills right

  12. Neuroergonomics Deep Dive Literature Review, Volume 2: Neuroergonomics and Performance: Prediction, Assessment, and Facilitation

    DTIC Science & Technology

    2010-11-01

    Monaco, A.P. (2009). A whole-genome scan and fine-mapping linkage study of auditory-visual synesthesia reveals evidence of linkage to chromosomes...2q24, 5q33, 6p12, and 12p12. American Journal of Human Genetics, 84 (2), 279-85. Synesthesia is characterized by anomalous sensory perception and...inheritance was likely to be more complex. These authors thus conducted a whole-genome linkage scan for auditory-visual synesthesia . Significant

  13. SOLFEAS: An Interactive Program for Estimating the Economic Feasibility of an Active Solar Thermal Energy System.

    DTIC Science & Technology

    1983-01-01

    7 Background Purpose Approach Scope Mode of Technology Transfer 2 SOLAR SYSTEM THERMAL ANALYSIS...collectors and employs sensible heat storage; however, it does not consider passive solar techniques at this time. Mode of Technology Transfer The information...1>23050 L, P, G, OR R? ARRAY Nt!MBER? EG. 6 I>5 bV HOT WATER LOAD, MBTU(MONTH), MONTH1,2,...12 E1TER 12 MONIlS DATA: QI,Q2 ...... ,Q12 I

  14. Initial Strategies for Tactical Operations Systems (TOS) Support of the Command and Control Process. Volume 2. Description of TOS Functions for Division Elements

    DTIC Science & Technology

    1978-06-01

    Description of TOS Functions for Division Elements by B. R. Modisette R. R. Michel G. W. Stevens S1STEM DEVELOPMENT CORPORATION Santa Monica, California...contract to the Department of the Army System Development Corporation 4 NOTICES DISTRIBUTION Primary distribution of this report has beer. made by...NAME AND ADDRESSv0 PROGRAM ELEMENT. PROJECT TAStK ~~ System Development Corporation N 6 2Q7627 2A765~ 2500 Colorado Avenue 2234A7 Santa Monica

  15. Atmospheric Optical Communication Systems.

    DTIC Science & Technology

    1981-02-01

    Tnteral system noise due to dark current id is Oven by . 1d = 2qGrB"" (2-9) Dark current is due to detecor biasing in some instances, and in somue...8217 without extansive pro- gr-=:ing exer’ence. Although. the znodel is designed to be Lteracdve, slight mod-.- i~cadons winl ezw :&31 r~ing of the progrsm

  16. Mechanism of inhibition of GluA2 AMPA receptor channel opening by 2,3-benzodiazepine derivatives: functional consequences of replacing a 7,8-methylenedioxy with a 7,8-ethylenedioxy moiety.

    PubMed

    Qneibi, Mohammad S; Micale, Nicola; Grasso, Silvana; Niu, Li

    2012-02-28

    2,3-Benzodiazepine (2,3-BDZ) compounds are a group of AMPA receptor inhibitors and are drug candidates for treating neurological diseases involving excessive AMPA receptor activity. We investigated the mechanism by which GluA2Q(flip) receptor channel opening is inhibited by two 2,3-BDZ derivatives, i.e., 1-(4-aminophenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (2,3-BDZ-11-2) and its 1-(4-amino-3-chlorophenyl) analogue (2,3-BDZ-11-4). Both compounds have a 7,8-ethylenedioxy moiety instead of the 7,8-methylenedioxy feature present in the structure of GYKI 52466, the prototypic 2,3-BDZ compound. Using a laser-pulse photolysis approach with a time resolution of ~60 μs and a rapid solution flow technique, we characterized the effect of the two compounds on the channel opening process of the homomeric GluA2Q(flip) receptor. We found that both 2,3-BDZ-11-2 and 2,3-BDZ-11-4 are noncompetitive inhibitors with specificity for the closed-channel conformation of the GluA2Q(flip) receptor. However, 2,3-BDZ-11-4 is ~10-fold stronger, defined by its inhibition constant for the closed-channel conformation (i.e., K(I) = 2 μM), than 2,3-BDZ-11-2. From double-inhibitor experiments, we determined that both compounds bind to the same site, but this site is different from two other known, noncompetitive binding sites on the GluA2Q(flip) receptor previously reported. Our results provide both mechanistic clues to improve our understanding of AMPA receptor regulation and a structure-activity relationship for designing more potent 2,3-BDZ compounds with predictable properties for this new noncompetitive site.

  17. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems.

    PubMed

    Williams, Stephen R; Aldred, Micheala A; Der Kaloustian, Vazken M; Halal, Fahed; Gowans, Gordon; McLeod, D Ross; Zondag, Sara; Toriello, Helga V; Magenis, R Ellen; Elsea, Sarah H

    2010-08-13

    Brachydactyly mental retardation syndrome (BDMR) is associated with a deletion involving chromosome 2q37. BDMR presents with a range of features, including intellectual disabilities, developmental delays, behavioral abnormalities, sleep disturbance, craniofacial and skeletal abnormalities (including brachydactyly type E), and autism spectrum disorder. To date, only large deletions of 2q37 have been reported, making delineation of a critical region and subsequent identification of candidate genes difficult. We present clinical and molecular analysis of six individuals with overlapping deletions involving 2q37.3 that refine the critical region, reducing the candidate genes from >20 to a single gene, histone deacetylase 4 (HDAC4). Driven by the distinct hand and foot anomalies and similar cognitive features, we identified other cases with clinical findings consistent with BDMR but without a 2q37 deletion, and sequencing of HDAC4 identified de novo mutations, including one intragenic deletion probably disrupting normal splicing and one intragenic insertion that results in a frameshift and premature stop codon. HDAC4 is a histone deacetylase that regulates genes important in bone, muscle, neurological, and cardiac development. Reportedly, Hdac4(-/-) mice have severe bone malformations resulting from premature ossification of developing bones. Data presented here show that deletion or mutation of HDAC4 results in reduced expression of RAI1, which causes Smith-Magenis syndrome when haploinsufficient, providing a link to the overlapping findings in these disorders. Considering the known molecular function of HDAC4 and the mouse knockout phenotype, taken together with deletion or mutation of HDAC4 in multiple subjects with BDMR, we conclude that haploinsufficiency of HDAC4 results in brachydactyly mental retardation syndrome.

  18. Protective and Therapeutic Agents for War Gases: Therapeutic Agents for Mustard and Nitrogen Mustards 2

    DTIC Science & Technology

    1946-01-10

    amount of product), made strongly alkaline with concentrated ammonia while cooling In ice, and filtered. The crude free base thus obtained was...SK Step III. Isolation of Crude ^-Amlno-3-mercaptobenzolc Acid (NDR-602^ (N.B. S2Q1-12S^ A caustic hydrolysate containing O.652 mole of...porcelain evaporating dish and dried under vacuum over P20c for two to three days. The crude faintly greenish solid contained large amounts of

  19. An Investigation of Geometric Radar Shapes for Stereotyping

    DTIC Science & Technology

    1981-08-01

    COSBY JOSEPH ZEIDNER Colonel, IN Technical Director Commander NOTICES DISTRIBUTION: Primary distribution of this report has been made by ARI. Please...Department of the Army position , unless so designated by other authorized documents. UNCLASSI FIED SECURITY CLASSIFICATION OF THIS PAGE Whwn Dete Entered...under Army Project 2Q762722A765 and is responsive to the needs of the U.S. Army Air Defense School , Directorate of Combat Developments, Fort Bliss

  20. Delineation of a minimal region of deletion at 6q16.3 in follicular lymphoma and construction of a bacterial artificial chromosome contig spanning a 6-megabase region of 6q16-q21.

    PubMed

    Henderson, Laura-Jane; Okamoto, Ichiro; Lestou, Valia S; Ludkovski, Olga; Robichaud, Marc; Chhanabhai, Mukesh; Gascoyne, Randy D; Klasa, Richard J; Connors, Joseph M; Marra, Marco A; Horsman, Douglas E; Lam, Wan L

    2004-05-01

    Regional deletions of 6q are frequent karyotypic alterations in malignant lymphoma and are associated with an adverse clinical outcome. One such region of recurrent deletion is 6q16-q21; however, the specific genes affected have not been identified. Our objective in this study was to identify cases with deletion of 6q16-q21 in follicular lymphoma and to define a minimal region of deletion. A physical map of 6q16.2-q21 was constructed using map information from both sequence-based and bacterial artificial chromosome (BAC) fingerprint-based maps. Forty-three BAC clones spanning a 6-Mb region of 6q16.2-q21 were identified and obtained from the RP-11 library. Selected BACs were fluorescence-labeled and hybridized to a series of 34 follicular lymphomas with a regional 6q deletion detected by G banding. Twenty-four cases with deletion of the 6q16.3 region were detected. A minimal deletion of 2.3 Mb was defined. Our study has identified a limited region of deletion of 6q16.3 that may implicate four known genes in follicular lymphoma and possibly in other cancers. A BAC contig spanning a 6-Mb region has been anchored to the 6q16.2-q21 region. This map represents a useful resource for gene identification in this region, not only in lymphoma but also in other neoplasms with 6q alterations.

  1. First-Principles Study of Nuclear Quadruple Interaction of ^19F* and Binding in Solid Fluorine

    NASA Astrophysics Data System (ADS)

    Mishra, D. R.; Aryal, M. M.; Adhikari, N. P.; Badu, S. R.; Pink, R. H.; Scheicher, R. H.; Chow, Lee; Das, T. P.

    2010-03-01

    We have studied the binding energy (BE) and nuclear quadrupule interaction (NQI) parameters for the ^19F* excited nuclear state in solid fluorine as part of our investigation [1] of the properties of solid halogens using the first principles Hartree-Fock Cluster procedure combined with many-body perturbation theory (MBPT), implemented by the Gaussian set of programs. Our results show that Van der Waals interaction obtained from intermolecular electron correlation effects has dominant influence on the BE but negligible effect on the NQI parameters. For the latter, ourcalculated e^2qQ is 119.0MHz using for Q(19F*), the value of 0.072 *10-28m2 [2], and η, the asymmetry parameter, is essentially zero. The influence of rotational vibrational effects on e^2qQ is being investigated using a first-principles procedure [3] to bridge the small remaining difference with experiment (127.2 MHz) for e^2qQ [4]. [1] M.M. Aryal et al., Hyperfine Interact, 176, 51 (2007). [2] K.C.Mishra et al.,Phys. Rev.B25, 3389(1982). [3] N. Sahoo et al. Phys. Rev. Lett. 50, 913(1983) [4] H. Barfuss et al., Phys. Lett. 90A, 33(1982)

  2. DNA-based nanostructures: The effect of the base sequence on octamer formation from d(XGGYGGT) tetramolecular G-quadruplexes.

    PubMed

    D'Atri, Valentina; Borbone, Nicola; Amato, Jussara; Gabelica, Valérie; D'Errico, Stefano; Piccialli, Gennaro; Mayol, Luciano; Oliviero, Giorgia

    2014-04-01

    In a previous work we have demonstrated that the DNA sequence CGGTGGT folds into a higher order G-quadruplex structure (2Q), obtained by the 5'-5' stacking of two unusual G(:C):G(:C):G(:C):G(:C) planar octads belonging to two identical tetra-stranded parallel quadruplexes, when annealed in the presence of ammonium or potassium ions. In the present paper, we discuss the role played by the title nucleosides X and Y (where X and Y stand for A, C, G, or T) on the formation and stability of 2Q structures formed by the XGGYGGT oligodeoxynucleotides. We found that the above mentioned dimerization pathway is not peculiar to the CGGTGGT sequence, but is possible for all the remaining CGGYGGT sequences (with Y = A, C, or G). Furthermore, we have found that the TGGAGGT sequence, despite the absence of the 5'-ending C, is also capable of forming a 2Q-like higher order quadruplex by using a slightly different dimerization interface, as characterized by NMR spectroscopy. To the best of our knowledge, this is the first characterization of a quadruplex multimer formed by an oligodeoxynucleotide presenting a thymine at its 5'-end. Examples of such structures were observed previously only in crystals and in the presence of non-physiological cations. Our results expand the repertoire of DNA quadruplex nanostructures of chosen length and add further complexity to the structural polymorphism of G-rich DNA sequences.

  3. Pharmacophore modeling, 3D-QSAR, and in silico ADME prediction of N-pyridyl and pyrimidine benzamides as potent antiepileptic agents.

    PubMed

    Malik, Ruchi; Mehta, Pakhuri; Srivastava, Shubham; Choudhary, Bhanwar Singh; Sharma, Manish

    2016-09-08

    Biological mechanism attributing mutations in KCNQ2/Q3 results in benign familial neonatal epilepsy (BFNE), a rare form of epilepsy and thus neglected. It offers a potential target for antiepileptic drug discovery. In the present work, a pharmacophore-based 3D-QSAR model was generated for a series of N-pyridyl and pyrimidine benzamides possessing KCNQ2/Q3 opening activity. The pharmacophore model generated contains one hydrogen bond donor (D), one hydrophobic (H), and two aromatic rings (R). They are the crucial molecular write-up detailing predicted binding efficacy of high affinity and low affinity ligands for KCNQ2/Q3 opening activity. Furthermore, it has been validated by using a biological correlation between pharmacophore hypothesis-based 3D-QSAR variables and functional fingerprints of openers responsible for the receptor binding and also by docking of these benzamides into the validated homology model. Excellent statistical computational tools of QSAR model such as good correlation coefficient (R(2 )>( )0.80), higher F value (F > 39), and excellent predictive power (Q(2) > 0.7) with low standard deviation (SD <0.3) strongly suggest that the developed model could be used for prediction of antiepileptic activity of newer analogs. A preliminary pharmacokinetic profile of these derivatives was also performed on the basis of QikProp predictions.

  4. Deletion of UBE3A in brothers with Angelman syndrome at the breakpoint with an inversion at 15q11.2.

    PubMed

    Kuroda, Yukiko; Ohashi, Ikuko; Saito, Toshiyuki; Nagai, Jun-Ichi; Ida, Kazumi; Naruto, Takuya; Wada, Takahito; Kurosawa, Kenji

    2014-11-01

    Angelman syndrome (AS) is characterized by severe intellectual disability with ataxia, epilepsy, and behavioral uniqueness. The underlining molecular deficit is the absence of the maternal copy of the imprinted UBE3A gene due to maternal deletions, which is observed in 70-75% of cases, and can be detected using fluorescent in situ hybridization (FISH) of the UBE3A region. Only a few familial AS cases have been reported with a complete deletion of UBE3A. Here, we report on siblings with AS caused by a microdeletion of 15q11.2-q12 encompassing UBE3A at the breakpoint of an inversion at 15q11.2 and 15q26.1. Karyotyping revealed an inversion of 15q, and FISH revealed the deletion of the UBE3A region. Array comparative genomic hybridization (CGH) demonstrated a 467 kb deletion at 15q11.2-q12, encompassing only UBE3A, SNORD115, and PAR1, and a 53 kb deletion at 15q26.1, encompassing a part of SLCO3A1. Their mother had a normal karyotype and array CGH detected no deletion of 15q11.2-q12, so we assumed gonadal mosaicism. This report describes a rare type of familial AS detected using the D15S10 FISH test.

  5. Complex chromosomal rearrangement in a girl with psychomotor-retardation and a de novo inversion: inv(2)(p15;q24.2).

    PubMed

    Granot-Hershkovitz, Einat; Raas-Rothschild, Annick; Frumkin, Ayala; Granot, David; Silverstein, Shira; Abeliovich, Dvorah

    2011-08-01

    Cytogenetic analysis of DNA from a girl with severe psychomotor retardation revealed a de novo pericentric inversion of chromosome 2: 46,XX,inv(2)(p15q24.2). In order to elucidate the possible role of the inversion in the girl's abnormal phenotype, we analyzed the inversion breakpoints. FISH analysis revealed BAC clones spanning the breakpoints at 2p and 2q of the inversion. Southern blot hybridization with DNA probes from the BAC regions was used to refine the localization of the breakpoints, followed by inverse-PCR which enabled us to sequence the inversion breakpoints. We found a complex chromosomal rearrangement, including five breakpoints, four at 2q and one at 2p joined with minor insertions/deletions of a few bases. The breakpoint at 2p was within the NRXN1 gene that has previously been associated with autism, intellectual disabilities, and psychiatric disorders. In 2q, the breakpoints disrupted two genes, TANC1 and RBMS1; the phenotypic effect of these genes is not currently known.

  6. Theory for ^77Se and ^125Te Nuclear Quadrupole Interactions in Selenium and Tellurium.

    NASA Astrophysics Data System (ADS)

    Suck-Cho, Hwa; Oh, Young-Kee; Park, Jin-Ho; Das, T. P.

    1998-03-01

    The electric field gradient(efg) tensors at ^77Se and ^125Te nuclei have been studied for the four systems involving each of these nuclei in both Selenium and Tellurium crystals utilizing the first principles Hartee-Fock Cluster procedure. Using the calculated efg for the pure systems and the experimental quadrupole coupling constants (e^2qQ), the quadrupole moments are determined to be Q(^77Se)=0.74±0,07(b) and Q(^125Te)=0.35±0.04(b). Comparison will be made with earlier values for the Q of the two nuclei. Using our values of Q and the calculated efg for ^77Se in tellurium and ^125Te in selenium, our values of e^2qQ agree within 15 per cent with that of experiment. The asymmetry parametrs η also agree reasonably well with experiment, but not as closely as the e^2qQ. Experimental results for η for ^125Te in selenium are needed to compare with theory.

  7. Hartree-Fock-Cluster Investigation of Nuclear Quadrupole Interactions in Solid Chalcogens, Selenium and Tellurium.

    NASA Astrophysics Data System (ADS)

    Aryal, M. M.; Maharjan, N. B.; Paudyal, D. D.; Mishra, D. R.; Byahut, S. R.; Scheicher, R. H.; Badu, S. R.; Jeong, J.; Chow, Lee; Das, T. P.

    2008-03-01

    Using the first-principles Hartree-Fock Cluster Procedure, we have studied the electronic structures of pure chain like Selenium and Tellurium, pure ring structured Selenium, Tellurium impurity in chain and ring-structured Selenium and Selenium impurity in chain-structured Tellurium chain. For our investigations in all the systems we have carried out convergence studies with respect to variational basis set sizes,sizes of clusters and electron correlation effects using many-body perturbation theory. Using our calculated electronic field-gradient parameters q in the pure chain systems and employing the experimental quadrupole coupling constants (e^2qQ), the values Q(^77Se)=(0.50±0.04) 10-28 m^2 and Q(^125Te)=-(0.2±0.02) 10-28m^2. Results will also be presented for the asymmetry parameters η for the pure chain systems and the e^2qQ and η for ^77Se in selenium ring. Our calculated values for e^2qQ and η for the impurity systems will also be presented and compared with available experimental data and earlier theoretical results.

  8. Identification of neurofibromatosis 1 (NF1) homologous loci by direct sequencing, fluorescence in situ hybridization, and PCR amplification of somatic cell hybrids

    SciTech Connect

    Purandare, S.M.; Neil, S.M.; Brothman, A. |

    1995-12-10

    Using fluorescence in situ hybridization (FISH), we have identified seven NF1-related loci, two separate loci on chromosome 2, at bands 2q21 and 2q33-q34, and one locus each on five other chromosomes at bands 14q11.2, 15q11.2, 18p11.2, 21q11.2-q21, and 22q11.2. Application of PCR using NF1 primer pairs and genomic DNA from somatic cell hybrids confirmed the above loci, identified additional loci on chromosomes 12 and 15, and showed that the various loci do not share homology beyond NF1 exon 27b. Sequenced PCR products representing segments corresponding to NF1 exons from these loci demonstrated greater than 95% sequence identity with the NF1 locus. We used sequence differences between bona fide NF1 and NF1-homologous loci to strategically design primer sets to specifically amplify 30 of 36 exons within the 5{prime} end of the NF1 gene. These developments have facilitated mutation analysis at the NF1 locus using genomic DNA as template. 41 refs., 3 figs., 3 tabs.

  9. Quantum integrable systems related to lie algebras

    NASA Astrophysics Data System (ADS)

    Olshanetsky, M. A.; Perelomov, A. M.

    1983-03-01

    Some quantum integrable finite-dimensional systems related to Lie algebras are considered. This review continues the previous review of the same authors [83] devoted to the classical aspects of these systems. The dynamics of some of these systems is closely related to free motion in symmetric spaces. Using this connection with the theory of symmetric spaces some results such as the forms of spectra, wave functions, S-matrices, quantum integrals of motion are derived. In specific cases the considered systems describe the one-dimensional n-body systems interacting pairwise via potentials g2v( q) of the following 5 types: vI( q) = q-2, vII( q) = sinh-2q, vIII( q) = sin-2q, v IV(q) = P(q) , vV( q) = q-2 + ω2q2. Here P(q) is the Weierstrass function, so that the first three cases are merely subcases of the fourth. The system characterized by the Toda nearest-neighbour potential exp( qjqj+ 1 ) is moreover considered. This review presents from a general and universal point of view results obtained mainly over the past fifteen years. Besides, it contains some new results both of physical and mathematical interest.

  10. Neurodevelopmental outcome in Angelman syndrome: genotype-phenotype correlations.

    PubMed

    Mertz, Line Granild Bie; Thaulov, Per; Trillingsgaard, Anegen; Christensen, Rikke; Vogel, Ida; Hertz, Jens Michael; Ostergaard, John R

    2014-07-01

    Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved.

  11. Chromosome region-specific libraries for human genome analysis

    SciTech Connect

    Kao, Fa-Ten.

    1992-08-01

    During the grant period progress has been made in the successful demonstration of regional mapping of microclones derived from microdissection libraries; successful demonstration of the feasibility of converting microclones with short inserts into yeast artificial chromosome clones with very large inserts for high resolution physical mapping of the dissected region; Successful demonstration of the usefulness of region-specific microclones to isolate region-specific cDNA clones as candidate genes to facilitate search for the crucial genes underlying genetic diseases assigned to the dissected region; and the successful construction of four region-specific microdissection libraries for human chromosome 2, including 2q35-q37, 2q33-q35, 2p23-p25 and 2p2l-p23. The 2q35-q37 library has been characterized in detail. The characterization of the other three libraries is in progress. These region-specific microdissection libraries and the unique sequence microclones derived from the libraries will be valuable resources for investigators engaged in high resolution physical mapping and isolation of disease-related genes residing in these chromosomal regions.

  12. Chromosome region-specific libraries for human genome analysis. Progress report, September 1, 1991--August 31, 1992

    SciTech Connect

    Kao, Fa-Ten

    1992-08-01

    During the grant period progress has been made in the successful demonstration of regional mapping of microclones derived from microdissection libraries; successful demonstration of the feasibility of converting microclones with short inserts into yeast artificial chromosome clones with very large inserts for high resolution physical mapping of the dissected region; Successful demonstration of the usefulness of region-specific microclones to isolate region-specific cDNA clones as candidate genes to facilitate search for the crucial genes underlying genetic diseases assigned to the dissected region; and the successful construction of four region-specific microdissection libraries for human chromosome 2, including 2q35-q37, 2q33-q35, 2p23-p25 and 2p2l-p23. The 2q35-q37 library has been characterized in detail. The characterization of the other three libraries is in progress. These region-specific microdissection libraries and the unique sequence microclones derived from the libraries will be valuable resources for investigators engaged in high resolution physical mapping and isolation of disease-related genes residing in these chromosomal regions.

  13. A class of constacyclic BCH codes and new quantum codes

    NASA Astrophysics Data System (ADS)

    liu, Yang; Li, Ruihu; Lv, Liangdong; Ma, Yuena

    2017-03-01

    Constacyclic BCH codes have been widely studied in the literature and have been used to construct quantum codes in latest years. However, for the class of quantum codes of length n=q^{2m}+1 over F_{q^2} with q an odd prime power, there are only the ones of distance δ ≤ 2q^2 are obtained in the literature. In this paper, by a detailed analysis of properties of q2-ary cyclotomic cosets, maximum designed distance δ _{max} of a class of Hermitian dual-containing constacyclic BCH codes with length n=q^{2m}+1 are determined, this class of constacyclic codes has some characteristic analog to that of primitive BCH codes over F_{q^2}. Then we can obtain a sequence of dual-containing constacyclic codes of designed distances 2q^2<δ ≤ δ _{max}. Consequently, new quantum codes with distance d > 2q^2 can be constructed from these dual-containing codes via Hermitian Construction. These newly obtained quantum codes have better code rate compared with those constructed from primitive BCH codes.

  14. Spiral-spin-driven ferroelectricity in a multiferroic delafossite AgFeO2.

    PubMed

    Terada, Noriki; Khalyavin, Dmitry D; Manuel, Pascal; Tsujimoto, Yoshihiro; Knight, Kevin; Radaelli, Paolo G; Suzuki, Hiroyuki S; Kitazawa, Hideaki

    2012-08-31

    We have performed dielectric measurements and neutron diffraction experiments on the delafossite AgFeO2. A ferroelectric polarization P is approximately equal to 300 μC/m2 was observed in a powder sample, below 9 K. The neutron diffraction experiment demonstrated successive magnetostructural phase transitions at T(N1)=15 K and T(N2)=9 K. The magnetic structure for 9 K≤T≤15 K is a spin-density wave with a temperature dependent incommensurate modulation k=(-1, q, 1/2), q is approximately equal to 0.384. Below 9 K, the magnetic structure turns into elliptical cycloid with the incommensurate propagation vector k=(-1/2,q,1/2), q is approximately equal to 0.2026 Based on the deduced magnetic point-group symmetry m1' of the low-temperature polar phase, we conclude that the ferroelectric polarization in AgFeO2 is perpendicular to the monoclinic b axis and is driven by the inverse Dzyaloshinskii-Moriya effect with two orthogonal components p1 is proportional to r(ij)×(S(i)×S(j)) and p2 is proportional to S(i)×S(j).

  15. Construction and accuracy of partial differential equation approximations to the chemical master equation.

    PubMed

    Grima, Ramon

    2011-11-01

    The mesoscopic description of chemical kinetics, the chemical master equation, can be exactly solved in only a few simple cases. The analytical intractability stems from the discrete character of the equation, and hence considerable effort has been invested in the development of Fokker-Planck equations, second-order partial differential equation approximations to the master equation. We here consider two different types of higher-order partial differential approximations, one derived from the system-size expansion and the other from the Kramers-Moyal expansion, and derive the accuracy of their predictions for chemical reactive networks composed of arbitrary numbers of unimolecular and bimolecular reactions. In particular, we show that the partial differential equation approximation of order Q from the Kramers-Moyal expansion leads to estimates of the mean number of molecules accurate to order Ω(-(2Q-3)/2), of the variance of the fluctuations in the number of molecules accurate to order Ω(-(2Q-5)/2), and of skewness accurate to order Ω(-(Q-2)). We also show that for large Q, the accuracy in the estimates can be matched only by a partial differential equation approximation from the system-size expansion of approximate order 2Q. Hence, we conclude that partial differential approximations based on the Kramers-Moyal expansion generally lead to considerably more accurate estimates in the mean, variance, and skewness than approximations of the same order derived from the system-size expansion.

  16. Significant In Vivo Anti-Inflammatory Activity of Pytren4Q-Mn a Superoxide Dismutase 2 (SOD2) Mimetic Scorpiand-Like Mn (II) Complex

    PubMed Central

    Serena, Carolina; Calvo, Enrique; Clares, Mari Paz; Diaz, María Luisa; Chicote, Javier U.; Beltrán-Debon, Raúl; Fontova, Ramón; Rodriguez, Alejandro; García-España, Enrique; García-España, Antonio

    2015-01-01

    Background The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight. Background/Methodology We have recently reported that two SOD mimetic compounds, the MnII complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q MnII complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin. Principal Findings In this report we show that the MnII complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules. Conclusion/Significance The effective anti-inflammatory activity of the MnII complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies. PMID:25742129

  17. Modulating the Redox Potential of the Stable Electron Acceptor, QB, in Mutagenized Photosystem II Reaction Centers.

    SciTech Connect

    Perrine, Zoee; Sayre, Richard

    2011-02-10

    One of the unique features of electron transfer processes in photosystem II (PSII) reaction centers (RC) is the exclusive transfer of electrons down only one of the two parallel cofactor branches. In contrast to the RC core polypeptides (psaA and psaB) of photosystem I (PSI), where electron transfer occurs down both parallel redox-active cofactor branches, there is greater protein-cofactor asymmetry between the PSII RC core polypeptides (D1 and D2). We have focused on the identification of protein-cofactor relationships that determine the branch along which primary charge separation occurs (P680+/pheophytin-(Pheo)). We have previously shown that mutagenesis of the strong hydrogen-bonding residue, D1-E130, to less polar residues (D1-E130Q,H,L) shifted the midpoint potential of the PheoD1/PheoD1- couple to more negative values, reducing the quantum yield of primary charge separation. We did not observe, however, electron transfer down the inactive branch in D1-E130 mutants. The protein residue corresponding to D1-E130 on the inactive branch is D2-Q129 which presumably has a reduced hydrogen-bonding interaction with PheoD2 relative to the D1-E130 residue with PheoD1. Analysis of the recent 2.9 Å cyanobacterial PSII crystal structure indicated, however, that the D2-Q129 residue was too distant from the PheoD2 headgroup to serve as a possible hydrogen bond donor and directly impact its midpoint potential as well as potentially determine the directionality of electron transfer. Our objective was to characterize the function of this highly conserved inactive branch residue by replacing it with a nonconservative leucine or a conservative histidine residue. Measurements of Chl fluorescence decay kinetics and thermoluminescence studies indicate that the mutagenesis of D2-Q129 decreases the redox gap between QA and QB due to a lowering of the redox potential of QB. The

  18. A stop codon mutation in SCN9A causes lack of pain sensation.

    PubMed

    Ahmad, Sultan; Dahllund, Leif; Eriksson, Anders B; Hellgren, Dennis; Karlsson, Urban; Lund, Per-Eric; Meijer, Inge A; Meury, Luc; Mills, Tracy; Moody, Adrian; Morinville, Anne; Morten, John; O'donnell, Dajan; Raynoschek, Carina; Salter, Hugh; Rouleau, Guy A; Krupp, Johannes J

    2007-09-01

    The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied a Canadian family from Newfoundland with members who exhibit a congenital inability to experience pain. We have mapped the locus to a 13.7 Mb region on chromosome 2q (2q24.3-2q31.1). Screening of candidate genes in this region identified a protein-truncating mutation in SCN9A, which encodes for the voltage-gated sodium channel Na(v)1.7. The mutation is a C-A transversion at nucleotide 984 transforming the codon for tyrosine 328 to a stop codon. The predicted product lacks all pore-forming regions of Na(v)1.7. Indeed, expression of this altered gene in a cell line did not produce functional responses, nor did it cause compensatory effects on endogenous voltage-gated sodium currents when expressed in ND7/23 cells. Because a homozygous knockout of Na(v)1.7 in mice has been shown to be lethal, we explored why a deficiency of Na(v)1.7 is non-lethal in humans. Expression studies in monkey, human, mouse and rat tissue indicated species-differences in the Na(v)1.7 expression profile. Whereas in rodents the channel was strongly expressed in hypothalamic nuclei, only weak mRNA levels were detected in this area in primates. Furthermore, primate pituitary and adrenal glands were devoid of signal, whereas these two glands were mRNA-positive in rodents. This species difference may explain the non-lethality of the observed mutation in humans. Our data further establish Na(v)1.7 as a critical element of peripheral nociception in humans.

  19. Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.

    PubMed

    Plagnol, Vincent; Howson, Joanna M M; Smyth, Deborah J; Walker, Neil; Hafler, Jason P; Wallace, Chris; Stevens, Helen; Jackson, Laura; Simmonds, Matthew J; Bingley, Polly J; Gough, Stephen C; Todd, John A

    2011-08-01

    The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A).

  20. Genomewide Scan for Affective Disorder Susceptibility Loci in Families of a Northern Swedish Isolated Population

    PubMed Central

    Venken, Tine; Claes, Stephan; Sluijs, Samuël; Paterson, Andrew D.; van Duijn, Cornelia; Adolfsson, Rolf; Del-Favero, Jurgen; Van Broeckhoven, Christine

    2005-01-01

    We analyzed nine multigenerational families with ascertained affective spectrum disorders in northern Sweden's geographically isolated population of Västerbotten. This northern Swedish population, which originated from a limited number of early settlers ∼8,000 years ago, is genetically more homogeneous than outbred populations. In a genomewide linkage analysis, we identified three chromosomal loci with multipoint LOD scores (MPLOD) ⩾2 at 9q31.1-q34.1 (MPLOD 3.24), 6q22.2-q24.2 (MPLOD 2.48), and 2q33-q36 (MPLOD 2.26) under a recessive affected-only model. Follow-up genotyping with application of a 2-cM density simple-tandem-repeat (STR) map confirmed linkage at 9q31.1-q34.1 (MPLOD 3.22), 6q23-q24 (MPLOD 3.25), and 2q33-q36 (MPLOD 2.2). In an initial analysis aimed at identification of the underlying susceptibility genes, we focused our attention on the 9q locus. We fine mapped this region at a 200-kb STR density, with the result of an MPLOD of 3.70. Genealogical studies showed that three families linked to chromosome 9q descended from common founder couples ∼10 generations ago. In this ∼10-generation pedigree, a common ancestral haplotype was inherited by the patients, which reduced the 9q candidate region to 1.6 Mb. Further, the shared haplotype was observed in 4.2% of patients with bipolar disorder with alternating episodes of depression and mania, but it was not observed in control individuals in a patient-control sample from the Västerbotten isolate. These results suggest a susceptibility locus on 9q31-q33 for affective disorder in this common ancestral region. PMID:15614721

  1. ERBB4 Confers Risk for Polycystic Ovary Syndrome in Han Chinese

    PubMed Central

    Peng, Yingqian; Zhang, Wei; Yang, Ping; Tian, Ye; Su, Shizhen; Zhang, Changming; Chen, Zi-Jiang; Zhao, Han

    2017-01-01

    A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, ERBB4), rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different (P = 1.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (Padjusted = 2.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50), were not significantly different in the replication cohort. Our results demonstrate that ERBB4, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese. PMID:28195137

  2. Design and Participant Characteristics of a Randomized-Controlled Trial of Telemedicine for Smoking Cessation among Rural Smokers

    PubMed Central

    Mussulman, Laura; Ellerbeck, Edward F.; Cupertino, Paula; Preacher, Kristopher J.; Spaulding, Ryan; Catley, Delwyn; Cox, Lisa Sanderson; Lambart, Leah; Hunt, Jamie J.; Nazir, Niaman; Shireman, Theresa; Richter, Kimber P.

    2014-01-01

    Introduction In rural America cigarette smoking is prevalent, few cessation services are available, and healthcare providers lack the time and resources to help smokers quit. This paper describes the design and participant characteristics of Connect2Quit (C2Q), a randomized control trial (RCT) that tests the effectiveness and cost-effectiveness of integrated telemedicine counseling delivered by 2-way webcams mounted on desktop computers in participant's physician office examining rooms (ITM) versus quitline counseling delivered by telephone in participant's homes (Phone) for helping rural smokers quit. Methods/Design C2Q was implemented in twenty primary care and safety net clinics. Integrated Telemedicine consisted of real-time video counseling, delivered to patients in their primary care physician's (PCP) office. Phone counseling, was delivered to patients in their homes. All participants received educational materials and guidance in selecting cessation medications. Results The 566 participants were predominantly Caucasian (92%); 9% were Latino. Most (65%) earned < 200% of federal poverty level. One out of three lacked home internet access, 40% were not comfortable using computers, and only 4% had been seen by a doctor via telemedicine in the past. Hypertension, chronic lung disease, and diabetes were highly prevalent. Participants smoked nearly a pack a day and were highly motivated to quit. Discussion C2Q is reaching a rural low-income population, with comorbid chronic diseases, that would benefit greatly from quitting smoking. ITM is a good delivery model, which integrates care by holding counseling sessions in the patient's PCP office and keeps the primary care team updated on patients’ progress. PMID:24768940

  3. Expression of common fragile sites in two Ceboidea species: Saimiri boliviensis and Alouatta caraya (Primates: Platyrrhini)

    PubMed Central

    Fundia, Ariela; Gorostiaga, María; Mudry, Marta

    2000-01-01

    Fragile sites are points of preferential breakage that may be involved in chromosome rearrangements. Induction of common fragile sites (c-fra) and spontaneous breakage were analyzed in two New World Monkeys species: Saimiri boliviensis (SBO) and Alouatta caraya (ACA). Spontaneous chromosome aberrations were analyzed on untreated lymphocyte cultures with Brögger's formula (1977). SBO presented a low level of spontaneous breakage, while higher frequencies were detected in ACA in which bands 1q23; 2q13 and 11q19 were significantly affected (p < 0.01). The populational distribution of c-fra was analyzed by the Chi2 test in FUdR plus caffeine treated cultures. A total of 21 c-fra was identified in SBO and 24 in ACA. Fragile sites A1q33, B1p21, B4p14, C3q23 and C5q22 were identified in all analyzed SBO specimens. The most frequent c-fra identified in ACA specimens were 1q23, 1q31, 1q33, 2q22, 8q14, 12q31, 13q22, 14q15 and Xq22. Fragile sites A1q31, A1q33, B1q14, B3q13, B4q21 and Xq22 identified in SBO and 1q31, 1q33, 2q22, 4q21, 6q13, 13q22 and Xq22 from ACA were the most conserved sites. A low coincidence between the location of c-fra and that of heterochromatin and breakpoints involved in euchromatic rearrangements known for these genera, was established. PMID:14736409

  4. ERBB4 Confers Risk for Polycystic Ovary Syndrome in Han Chinese.

    PubMed

    Peng, Yingqian; Zhang, Wei; Yang, Ping; Tian, Ye; Su, Shizhen; Zhang, Changming; Chen, Zi-Jiang; Zhao, Han

    2017-02-14

    A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, ERBB4), rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different (P = 1.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (Padjusted = 2.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50), were not significantly different in the replication cohort. Our results demonstrate that ERBB4, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese.

  5. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    PubMed Central

    Broeks, Annegien; Schmidt, Marjanka K.; Sherman, Mark E.; Couch, Fergus J.; Hopper, John L.; Dite, Gillian S.; Apicella, Carmel; Smith, Letitia D.; Hammet, Fleur; Southey, Melissa C.; Van ’t Veer, Laura J.; de Groot, Renate; Smit, Vincent T.H.B.M.; Fasching, Peter A.; Beckmann, Matthias W.; Jud, Sebastian; Ekici, Arif B.; Hartmann, Arndt; Hein, Alexander; Schulz-Wendtland, Ruediger; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sinn, Hans-Peter; Sohn, Christof; Tchatchou, Sandrine; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Ørsted, David D.; Kaur-Knudsen, Diljit; Milne, Roger L.; Pérez, Jose I. Arias; Zamora, Pilar; Rodríguez, Primitiva Menéndez; Benítez, Javier; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon-Dschun; Hamann, Ute; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Chang-Claude, Jenny; Wang-Gohrke, Shan; Bremer, Michael; Karstens, Johann H.; Hillemanns, Peter; Dörk, Thilo; Nevanlinna, Heli A.; Heikkinen, Tuomas; Heikkilä, Päivi; Blomqvist, Carl; Aittomäki, Kristiina; Aaltonen, Kirsimari; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana M.; Kataja, Vesa; Auvinen, Päivi; Eskelinen, Matti; Soini, Ylermi; Chenevix-Trench, Georgia; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Holland, Helene; Lambrechts, Diether; Claes, Bart; Vandorpe, Thijs; Neven, Patrick; Wildiers, Hans; Flesch-Janys, Dieter; Hein, Rebecca; Löning, Thomas; Kosel, Matthew; Fredericksen, Zachary S.; Wang, Xianshu; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Grenaker Alnæs, Grethe; Kristensen, Vessela; Børresen-Dale, Anne-Lise; Hunter, David J.; Hankinson, Susan E.; Andrulis, Irene L.; Marie Mulligan, Anna; O'Malley, Frances P.; Devilee, Peter; Huijts, Petra E.A.; Tollenaar, Rob A.E.M.; Van Asperen, Christi J.; Seynaeve, Caroline S.; Chanock, Stephen J.; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Figueroa, Jonine; Yang, Xiaohong R.; Hooning, Maartje J.; Hollestelle, Antoinette; Oldenburg, Rogier A.; Jager, Agnes; Kriege, Mieke; Ozturk, Bahar; van Leenders, Geert J.L.H.; Hall, Per; Czene, Kamila; Humphreys, Keith; Liu, Jianjun; Cox, Angela; Connley, Daniel; Cramp, Helen E.; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W.R.; Dunning, Alison M.; Easton, Douglas F.; Humphreys, Manjeet K.; Caldas, Carlos; Blows, Fiona; Driver, Kristy; Provenzano, Elena; Lubinski, Jan; Jakubowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Gronwald, Jacek; Brennan, Paul; Sangrajrang, Suleeporn; Gaborieau, Valerie; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Hou, Ming-Feng; Huang, Chiun-Sheng; Anton-Culver, Hoda; Ziogas, Argyrios; Pharoah, Paul D.P.; Garcia-Closas, Montserrat

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER− tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10−18), rs3803662 (16q12) (P = 3.7 × 10−5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10−6 and P = 4.1 × 10−4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment. PMID:21596841

  6. Observation of an Unusual Electronically Distorted Semiquinone Radical of PCB Metabolites in the Active Site of Prostaglandin H Synthase-2

    PubMed Central

    Wangpradit, Orarat; Moman, Edelmiro; Nolan, Kevin B.; Buettner, Garry R.; Robertson, Larry W.; Luthe, Gregor

    2013-01-01

    The activation of the metabolites of airborne polychlorinated biphenyls (PCBs) into highly reactive radicals is of fundamental importance. We found that human recombinant prostaglandin H synthase-2 (hPGHS-2) biotransforms dihydroxy-PCBs, such as 4-chlorobiphenyl-2′,5′-hydroquinone (4-CB-2′,5′H2Q), into semiquinone radicals via one-electron oxidation. Using electron paramagnetic resonance (EPR) spectroscopy, we observed the formation of the symmetric quartet spectrum (1:3:3:1 by area) of 4-chlorobiphenyl-2′,5′-semiquinone radical (4-CB-2′,5′-SQ•−) from 4-CB-2′,5′H2Q. This spectrum changed to an asymmetric spectrum with time: the change can be explained as the overlap of two different semiquinone radical species. Hindered rotation of the 4-CB-2′,5′-SQ•− appears not to be a major factor for the change in lineshape because increasing the viscosity of the medium with glycerol produced no significant change in lineshape. Introduction of a fluorine, which increases the steric hindrance for rotation of the dihydroxy-PCB studied, also produced no significant changes. An in silico molecular docking model of 4-CB-2′,5′H2Q in the peroxidase site of hPGHS-2 together with ab initio quantum mechanical studies indicate that the close proximity of a negatively charged carboxylic acid in the peroxidase active site may be responsible for the observed perturbation in the spectrum. This study provides new insights into the formation of semiquinones from PCB metabolites and underscores the potential role of PGHS-2 in the metabolic activation of PCBs. PMID:20843536

  7. Partial trisomy 5q resulting from chromosome 7 insertion: An expansion of the phenotype

    SciTech Connect

    Fries, M.H.; Reilly, P.A.; Williams, T.C.

    1994-09-01

    Partial trisomy 5q has been categorized into three separate phenotypes; however, a distinctive phenotype has not been described for duplications spanning 5q23-q35. We report a case of partial trisomy 5q for this region as a result of a ins(7,5)(q31.3;q23.2q35.1)mat. The liveborn male infant was delivered by emergency cesarean section at 37 weeks after a pregnancy notable for oligohydramnios, with birth weight 1792 g (<3%). Postnatal course was marked by psychomotor delay, failure to thrive, and biopsy demonstrated neonatal giant cell hepatitis with a paucity of intrahepatic bile ducts. His appearance was remarkable for lack of subcutaneous fat, midline displaced hair whorl, bitemporal narrowing with frontal bossing, wide anterior fontanel, widow`s peak, protuberant eyes with periorbital and lid edema, short flat nasal bridge with broad flattened nasal tip, long smooth philtrum, wide mouth with thin lips, wide gingival ridges, micrognathia, posteriorly rotated low-set ears, hepatomegaly, flexion contractions of elbows, and generalized hypertonicity. Urine organic acids, oligosaccharide/mucopolysaccharide screen, and plasma amino acids were negative. GTG-banding on prometaphase chromosomes showed an unbalanced translocation involving chr. 7. This was identified as an insertion of chr. 5 (q23.2q35.1) into distal 7q after FISH using chr. 5 and chr. 7 painting probes. The infant`s mother carries the balanced insertional rearrangement: 46,XX,dir ins(7,5)(q31.3;q23.2q35.1). This phenotype overlaps that of previously described duplications with the addition of giant cell hepatitis, coarsened facial features, gingival thickening, and flexion contractures, suggestive of a yet undiagnosed storage disorder.

  8. Laminar and turbulent incompressible fluid flow analysis with heat transfer by the finite element method

    SciTech Connect

    Cochran, R.J.

    1992-01-01

    A study of the finite element method applied to two-dimensional incompressible fluid flow analysis with heat transfer is performed using a mixed Galerkin finite element method with the primitive variable form of the model equations. Four biquadratic, quadrilateral elements are compared in this study--the serendipity biquadratic element with bilinear continuous pressure interpolation (Q2(8)-Q1) and the Lagrangian biquadratic element with bilinear continuous pressure interpolation (Q2-Q1) of the Taylor-Hood form. A modified form of the Q2-Q1 element is also studied. The pressure interpolation is augmented by a discontinuous constant shape function for pressure (Q2-Q1+). The discontinuous pressure element formulation makes use of biquadratic shape functions and a discontinuous linear interpolation of the pressure (Q2-P1(3)). Laminar flow solutions, with heat transfer, are compared to analytical and computational benchmarks for flat channel, backward-facing step and buoyancy driven flow in a square cavity. It is shown that the discontinuous pressure elements provide superior solution characteristics over the continuous pressure elements. Highly accurate heat transfer solutions are obtained and the Q2-P1(3) element is chosen for extension to turbulent flow simulations. Turbulent flow solutions are presented for both low turbulence Reynolds number and high Reynolds number formulations of two-equation turbulence models. The following three forms of the length scale transport equation are studied; the turbulence energy dissipation rate ([var epsilon]), the turbulence frequency ([omega]) and the turbulence time scale (tau). It is shown that the low turbulence Reynolds number model consisting of the K - [tau] transport equations, coupled with the damping functions of Shih and Hsu, provides an optimal combination of numerical stability and solution accuracy for the flat channel flow.

  9. Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

    SciTech Connect

    Trask, B.J.; Friedman, C.; Giorgi, D.

    1994-09-01

    We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

  10. Copper-catalyzed hydroquinone oxidation and associated redox cycling of copper under conditions typical of natural saline waters.

    PubMed

    Yuan, Xiu; Pham, A Ninh; Miller, Christopher J; Waite, T David

    2013-08-06

    A detailed kinetic model has been developed to describe the oxidation of Cu(I) by O2 and the reduction of Cu(II) by 1,4-hydroquinone (H2Q) in the presence of O2 in 0.7 M NaCl solution over a pH range of 6.5-8.0. The reaction between Cu(I) and O2 is shown to be the most important pathway in the overall oxidation of Cu(I), with the rate constant for this oxidation process increasing with an increasing pH. In 0.7 M NaCl solutions, Cu(II) is capable of catalyzing the oxidation of H2Q in the presence of O2 with the monoanion, HQ(-), the kinetically active hydroquinone form, reducing Cu(II) with an intrinsic rate constant of (5.0 ± 0.4) × 10(7) M(-1) s(-1). Acting as a chain-propagating species, the deprotonated semiquinone radical (SQ(•) (-)) generated from both the one-electron oxidation of H2Q and the one-electron reduction of 1,4-benzoquinone (BQ) also reacts rapidly with Cu(II) and Cu(I), with the same rate constant of (2.0 ± 0.5) × 10(7) M(-1) s(-1). In addition to its role in reformation of Cu(II) via continuous oxidation of Cu(I), O2 rapidly removes SQ(•) (-), resulting in the generation of O2(•) (-). Agreement between half-cell reduction potentials of different redox couples provides confirmation of the veracity of the proposed model describing the interactions of copper and quinone species in circumneutral pH saline solutions.

  11. Nonminimal coupling for the gravitational and electromagnetic fields: Black hole solutions and solitons

    SciTech Connect

    Balakin, Alexander B.; Bochkarev, Vladimir V.; Lemos, Jose P. S.

    2008-04-15

    Using a Lagrangian formalism, a three-parameter nonminimal Einstein-Maxwell theory is established. The three parameters q{sub 1}, q{sub 2}, and q{sub 3} characterize the cross-terms in the Lagrangian, between the Maxwell field and terms linear in the Ricci scalar, Ricci tensor, and Riemann tensor, respectively. Static spherically symmetric equations are set up, and the three parameters are interrelated and chosen so that effectively the system reduces to a one parameter only, q. Specific black hole and other type of one-parameter solutions are studied. First, as a preparation, the Reissner-Nordstroem solution, with q{sub 1}=q{sub 2}=q{sub 3}=0, is displayed. Then, we search for solutions in which the electric field is regular everywhere as well as asymptotically Coulombian, and the metric potentials are regular at the center as well as asymptotically flat. In this context, the one-parameter model with q{sub 1}{identical_to}-q, q{sub 2}=2q, q{sub 3}=-q, called the Gauss-Bonnet model, is analyzed in detail. The study is done through the solution of the Abel equation (the key equation), and the dynamical system associated with the model. There is extra focus on an exact solution of the model and its critical properties. Finally, an exactly integrable one-parameter model, with q{sub 1}{identical_to}-q, q{sub 2}=q, q{sub 3}=0, is considered also in detail. A special submodel, in which the Fibonacci number appears naturally, of this one-parameter model is shown, and the corresponding exact solution is presented. Interestingly enough, it is a soliton of the theory, the Fibonacci soliton, without horizons and with a mild conical singularity at the center.

  12. Functional analysis of polymorphisms in the promoter regions of genes on 22q11.

    PubMed

    Hoogendoorn, Bastiaan; Coleman, Sharon L; Guy, Carol A; Smith, S Kaye; O'Donovan, Michael C; Buckland, Paul R

    2004-07-01

    Segmental aneusomy, which includes chromosome 22 deletion syndrome (del(22)(q11.2q11.2)), has been associated with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face (CAF) syndrome, cat-eye syndrome (CES), der(22) syndrome, and duplication of the del(22)(q11.2q11.2) syndrome's typically deleted region. Adults with del(22)(q11.2q11.2) may develop psychiatric illnesses, including schizophrenia, schizoaffective disorder, and bipolar disorder, suggesting that lower gene dosage leads to a predisposition to these illnesses. In a bid to identify important regulatory polymorphisms (SNPs) that may emulate changes in gene dosage of the genes within the common deletion, we have analyzed the promoter region of 47 genes (44 of which encode a protein with known function) encoding proteins in and around 22q11 for sequence variants. A total of 33 of the promoters contained polymorphisms. Of those, 25 were cloned into a reporter gene vector, pGL3. The relative ability of each promoter haplotype to promote transcription of the luciferase gene was tested in each of two human cell lines (HEK293t and TE671), using a cotransfected CMV-SPAP plasmid as an internal control. Five genes (PRODH, DGCR14, GSTT2, SERPIND1, and a gene tentatively called DKFZP434P211) showed activity differences between haplotypes of greater than 1.5-fold. Of those, PRODH, which encodes proline dehydrogenase, has previously been highlighted in relation to schizophrenia, and the functional promoter polymorphism reported here may be involved in pathogenic mechanisms.

  13. The Potential Effect of Maturing Technology Upon Future Seaplanes

    DTIC Science & Technology

    2005-04-01

    0.0697 0.0049 0.0002 0.06296 0.0632 860,914 DRAG TABLE W/STEP: 1.0M Lb. Seaplane @ Sealevel )( )( Re_ 2 qS WC EAR CCd CdCdCD SqCDquiredThrust L L i...speed, loiter at sealevel for 30 minutes at optimum speed, and land without any fuel penalty. Brequet Range Equation 1.0M lb. SEAPLANE Ferry...FT/SEC C 0.5388 V 415.53 KTS Ferry Mission - Start, climb, cruise at best range cruise speed, loiter at sealevel for 30 minutes at optimum speed, and

  14. New results from the studies of the Ν (1440) 1/2+, Ν (1520) 3/2–, and Δ (1620) 1/2– resonances in exclusive ep → e'p'π+π– electroproduction with the CLAS detector

    DOE PAGES

    Mokeev, Viktor I.; Burkert, Volker D.; Carman, Daniel S.; ...

    2016-02-25

    In this study, the transition helicity amplitudes from the proton ground state to the N(1440)1/2+, N(1520)3/2–, and Δ(1620)1/2– resonances (γvpN* electrocouplings) were determined from the analysis of nine independent onefold differential π+π–p electroproduction cross sections off a proton target, taken with CLAS at photon virtualities 0.5GeV2 < Q2 < 1.5 GeV2. The phenomenological reaction model employed for separation of the resonant and nonresonant contributions to this exclusive channel was further developed.

  15. Fine-mapping of a QTL influencing pork tenderness on porcine chromosome 2

    PubMed Central

    Meyers, Stacey N; Rodriguez-Zas, Sandra L; Beever, Jonathan E

    2007-01-01

    Background In a previous study, a quantitative trait locus (QTL) exhibiting large effects on both Instron shear force and taste panel tenderness was detected within the Illinois Meat Quality Pedigree (IMQP). This QTL mapped to the q arm of porcine chromosome 2 (SSC2q). Comparative analysis of SSC2q indicates that it is orthologous to a segment of human chromosome 5 (HSA5) containing a strong positional candidate gene, calpastatin (CAST). CAST polymorphisms have recently been shown to be associated with meat quality characteristics; however, the possible involvement of other genes and/or molecular variation in this region cannot be excluded, thus requiring fine-mapping of the QTL. Results Recent advances in porcine genome resources, including high-resolution radiation hybrid and bacterial artificial chromosome (BAC) physical maps, were utilized for development of novel informative markers. Marker density in the ~30-Mb region surrounding the most likely QTL position was increased by addition of eighteen new microsatellite markers, including nine publicly-available and nine novel markers. Two newly-developed markers were derived from a porcine BAC clone containing the CAST gene. Refinement of the QTL position was achieved through linkage and haplotype analyses. Within-family linkage analyses revealed at least two families segregating for a highly-significant QTL in strong positional agreement with CAST markers. A combined analysis of these two families yielded QTL intervals of 36 cM and 7 cM for Instron shear force and taste panel tenderness, respectively, while haplotype analyses suggested further refinement to a 1.8 cM interval containing CAST markers. The presence of additional tenderness QTL on SSC2q was also suggested. Conclusion These results reinforce CAST as a strong positional candidate. Further analysis of CAST molecular variation within the IMQP F1 boars should enhance understanding of the molecular basis of pork tenderness, and thus allow for genetic

  16. Guide to the Business Capability Lifecycle for Department of Defense ACAT III Programs

    DTIC Science & Technology

    2012-07-01

    Cause and Effect matix SCAMPER Analysis Goal Quality Metrics Gap Analysis Bottlenecks Defects Goal Quality Metrics E2E Supported BPMN Q1/2 Q3 Q4 Q6 Q6...analysis a. Identify the root causes of the business problem b. Provide an as-is map, using Business Process Model and Notation ( BPMN ), of the...why they were eliminated from further consideration 8. To-be analysis a. Provide a to-be map, in BPMN , of the target process that illustrates the

  17. Bose-Einstein correlations in e/sup +/e/sup -/ collisions

    SciTech Connect

    Juricic, I.

    1987-12-01

    The MARK II detector is used to study the Bose-Einstein correlation between pairs and triplets of charged pions produced in hadronic decays of the J)psi), the ..sqrt..s = 4 to 7 GeV continuum above the J)psi), two photon events at ..sqrt..s = 29 GeV, and e/sup )plus/)e/sup )minus/) annihilation events at ..sqrt..s = 29 GeV as a function of Q/sup 2/, the four-momentum transfer squared. After corrections for Coulomb effects and pion misidentification, we find a nearly full Bose-Einstein enhancement ..cap alpha.. in the J)psi) and the two photon data and about half the maximum value in the other two data sets. The radius parameter )tau)(an average over space and time) given by pion pair analyses lies within a band of +-0.10 fm around 0.73 fm and is the same, within errors, for all four data sets. Pion triplet analyses also give a consistent radius of approx. 0.54 fm. fits to two-dimensional distributions R(q/sub T//sup 2/, q/sub C//sup 2/) of invariant components of Q/sup 2/ = q/sub T//sup 2/ )plus) q/sub C//sup 2/ give )tau)/sub T/ approx. )tau)C approx. )tau), where q/sub T/ is the transverse three-momentum difference calculated with respect to the net pair three-momentum, and q/sub C/ is in effect the longitudinal three-momentum difference in the pion pair rest frame. When q/sub T/ is calculated with respect to the jet axis for two-jet events in the e/sup )plus/)e/sup )minus/) annihilation data at ..sqrt..s = 29 GeV, a fit to R(q/sub T//sup 2/, q/sub C//sup 2/) also gives )tau)/sub T/ approx. )tau)/sub C/ approx. )tau). Noting that q/sub L/ and q/sub 0/ are not invariant, we make fits to R(/sub T//sup T/, q/sub L//sup 2/) and to R(q/sub T//sup 2/, q/sub 0//sup 2/) (Kopylov formulation), and we find )tau)/sub 0/ approx. )tau)/sub L/ approx. )23))tau)/sub T/ to )12))tau)/sub T/. 44 refs., 43 figs., 15 tabs

  18. Different proximal and distal rearrangements of chromosome 7q associated with holoprosencephaly.

    PubMed Central

    Benzacken, B; Siffroi, J P; Le Bourhis, C; Krabchi, K; Joyé, N; Maschino, F; Viguié, F; Soulié, J; Gonzales, M; Migné, G; Bucourt, M; Encha-Razavi, F; Carbillon, L; Taillemite, J L

    1997-01-01

    Four new cases of holoprosencephaly are described in fetuses exhibiting abnormal karyotypes with different distal and proximal rearrangements of the long arm of chromosome 7. Three of them showed terminal deletions of chromosome 7q, confirming the importance of the 7q36 region in holoprosencephaly. The karyotype of the fourth fetus showed an apparently balanced de novo translocation, t(7;13) (q21.2;q33), without any visible loss of the distal part of chromosome 7q. The involvement of new genes, different from the human Sonic Hedgehog gene (hShh) responsible for holoprosencephaly, or a positional effect are discussed. Images PMID:9391882

  19. The Air Force Acquisition Logistics Division (AFALD): Relationship of Aspects of Manpower to Mission Performance.

    DTIC Science & Technology

    1981-06-01

    BUJRtAU Of STANOARDS 196 A, L3.2 Q6 " *~ ~ 40A 4-i We" ....... Ir ’ gE ~ z Aecesslon For NTT C "A&I DTI," TAP Unawicaunced El Justification_ BY...significance? a. Highly b. Significant c . Slightly d. Of No Significant Significant Significance 5. Comaments: Name and Grade Position Organization...20. It dillferent 11ree Report) IS. SUPPLEMENTARY NOTES F3~R1 C . LYN~Zalm. USA Director of Public Affaius 13 0V 181 wiright-Pattrso FB, ONl 45433 Is

  20. Multiple Coupled Waveguide Laser Array.

    DTIC Science & Technology

    1986-11-05

    7 -17 448 MULTIPLE COUPLED UVEGUIDE LAER ARRRY(U) SCHAFER (N J) I/2 ASSOCIATES INC CHELMSFORD MR D G YOUMANS 65 NOVY8 WJS-FR-86-814 AFMAL-TR-86...a, h, c, d , e, f) ............. 77 2q. 1x7 Device with Gas Flow, Vacuum, Water and Electrical Connections .............................. .1 30. 1x7...k x)] exp [i(k z-Wt)] (12) x2 x2 Region 3. (ZnSe, n = 2.4) D exp [i(-k x + k z-Wt)] (13)x z II I. N *111 g .U 0 4 ’,. . . , . . . - " " - " . % z r

  1. Chromosomal aberrations suggestive of mutagen-related leukemia after 21 years of therapeutic radon exposure

    SciTech Connect

    Rechavi, G.; Berkowicz, M.; Rosner, E.; Neuman, Y.; Ben-Bassat, I.; Ramot, B. )

    1990-08-01

    A 68-year-old woman with acute myelomonocytic leukemia, who was treated annually for 21 consecutive years by therapeutic low-dose radon gas radiation because of spondyloarthritis, is described. The karyotype of the malignant clone was 45,XX, -17, -18,del(5)(q15q33), +t(17;18)(q11.2q23). In 45% of the metaphases, the modal number was between hyperdiploid to near tetraploid. Double minute chromosomes were demonstrated in 60% of the cells. These chromosomal aberrations are suggestive of mutagen-related leukemia.

  2. Logic Nanocells Within 3-Terminal Ordered Arrays

    DTIC Science & Technology

    2007-02-28

    listed in Table 1. Water Contact Angle Measurements. Contact angle measurements were performed using a Ram6-Hart goniometer model 100. Measurements...quantitatively. Molecule Measured Contact angle ellipsometric (0 static ) thickness (A) X=SH X=SCN X=SH X=SCN nC 12H25-X 16.4 12.2 105 97 0 /x 14.6 13.8...2q3x4/3)R30* for aromatics, Figures 3a- 0 16,17 occupied by those two elements. Contact angle and ellipsometry clearly support this assumption for

  3. The Structure of the Doppler-Difference Signal and the Analysis of Its Autocorrelation Function.

    DTIC Science & Technology

    1979-07-01

    I12tinuation or maximum entropy techniques, have also been proposed. However, they would all require a separate and distinct programme. A procedure...restrictions, the result can also be shown to hold if p uv is a 4 bivariate normal distribution, so that a shear stress term can be accommodated4 In this...100 times the maximum value of the second at resonance. Hence around u - u0 we take as a good approximation T sin 21Tr(q Pu(U) = 2 q_2 c - in terms of

  4. Mountain Home AFB, Mountain Home, Idaho. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1980-03-10

    and National Weather Service (USWB) Beginning thru 1945 at 08001ST Beginning thru Jun 52 at 0030GT Jan 46-May 47 at 1230GM Jul 52-May 57 at 123O Jun 57...onw + . of Hor .1 .’T. .. . ..o-ur. GLOBAL CLIMATOLOGY BRANCH USAFETAC PSYCHROMETRIC SUMMARY 11 AIR WEATER SERVICE /MAC 2q106 MOUNTAIN HOME AFB ID 68...Mar 80 Air Weather Service (MAC) 13 NUMBER OF PAGES Scott AFB IL 62225 P 14 MONITORING AGENCY NAME 6 AODRESS(it different Ito.. Controlling Office) IS

  5. Dissecting the Molecular Mechanism of RhoC GTPase Expression in the Normal and Malignant Breast

    DTIC Science & Technology

    2010-09-01

    times a segment of the genome is sequenced, which is currently much higher for short read than long read technologies. As such, the choice of technology...renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case, Cytogenet. Cell Genet. 71 (1995) 280–284. [66] V. Tonk...fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35), Am. J. Pathol. 156 (2000) 781–789

  6. Limnological Assessment of West Point Lake, Georgia

    DTIC Science & Technology

    1994-07-01

    accumulated sediments in a mainstem reservoir," M.S. Thesis , Clemson University. Bartolucci, L., and Chang, M. (1988). "Look-up tables to convert Landsat...based on coincident sample and Landsat Thematic Mapper data", M.S. thesis , Murray State University. Gaugush, R. F., ed. (1986). "Statistical methods...0: . . . . . . . . . . . . . . . C; 00 Q PM U2 Q 40 F. C C, t 0 0 Q- Qn 00anO 0 . . . . , .- . ~ . . . . . aC so i- Qdo o 0. 0 4

  7. Geostrophic Vortices on a Circle of Latitude in a Cap on a Rotating Sphere

    DTIC Science & Technology

    1974-07-01

    ieparture of the free outer surface of the layer from an equilibrium position is small; and that the tangen - tial acceleration is negligible compared...gjP [C(4.«,0) -20^^(^0,0)] ? a 2Q -THr^(*’e) The theory of Laplace transforms can be used to show that the steady state solution of (3.8) is...sin 0., where 5 symbolizes the Dirac delta function. Hence the basic equa- tion to be solved is ^ 1 .2 4a 2a)^ M-^M^^-V (3.^) ^^ineH

  8. Identification of Tumor Suppressor Genes by Genetic and Epigenetic Genome-Scanning

    DTIC Science & Technology

    2008-04-01

    genes that were found down-regulated in all 5 breast and 3 prostate cancer cell lines and the ESCO2 (set 20), GSHR (GSR) (set 26), NP_115712 (GINS4...the CH012, CH013, DEF1, EGR3, ESCO2, FBX25, GON1, GSHR , MYOM2, NP_065895, NP_115712, NP_859074, NP_001034551, NPM2, NRG1, PHYIP, PIWL2, Q6P464...cases), ESCO2, NP_115712 (8 cases), GSHR (7 cases). For the remaining genes, down-regulation was observed in 4 (NP_065895), 5 (TPA), or 6 cases (CH013

  9. Recurrent proximal 18p monosomy and 18q trisomy in a family due to a pericentric inversion.

    PubMed

    Zamani, Ayse Gul; Acar, Aynur; Durakbasi-Dursun, Gul; Yildirim, M Selman; Ceylaner, Serdar; Tuncez, Ebru

    2014-05-01

    Here, we report on a family with pericentric inversion of chromosome 18 [inv(18)(p11.2q21)] and two recombinants with a duplication of q21 → qter and a deletion of p11.2 → pter regions in a four-generation family. This chromosomal abnormality was inherited in our first patient from the father, while it was transmitted to the second patient from the mother. Array-CGH analysis were used to better characterize duplicated and deleted chromosomal regions and showed no genomic copy number variation (CNV) differences between these two relatives. We discussed genotype-phenotype correlations including previously reported.

  10. A Survey of Biodynamic Test Devices and Methods,

    DTIC Science & Technology

    1984-04-01

    failure. Animal tests are especially valuable in suggesting injury mechanisms that can occur under specified occupant-vehicle configurations. Comparison...Frequency RanCe 27000iz e.4, Number 1 e.4.a, on sled 21/2q e.4.b. on subject/dumrly f. Other Parameters Monitoreo : LUNG PRESSURE. BELT FORCES I IJ I...4.a. on ile_ _ _ v.4.u. un s.uject/ourvy I. Other Parameters Monitoreo : 40 NATO/AGARD Impact Test Facility Survey ID #33 1. Name and Address of

  11. Interstitial 11q24 deletion: a new case and review of the literature.

    PubMed

    Tassano, Elisa; Janis, Sara; Canepa, Alberto; Zanotto, Elisabetta; Torello, Corrado; Gimelli, Giorgio; Cuoco, Cristina

    2016-08-01

    We describe a 19-month-old male presenting with right stenotic megaureter, anemia and thrombocytopenia, cardiac and ophthalmologic abnormalities. Analysis with array-based comparative genomic hybridization (aCGH) revealed an interstitial deletion of about 2.4 Mb of chromosome 11q24.2q24.3. We compared the phenotype of our patient with that of recently reported patients studied by aCGH, who showed an overlapping deletion. We also analysed the gene content of the deleted region in order to investigate the possible involvement of specific genes in the clinical phenotype.

  12. Completeness of Derivatives of Squared Schroedinger Eigenfunctions and Explicit Solutions of the Linearized KdV Equation.

    DTIC Science & Technology

    1981-04-01

    Contract No. DAAG29- 10-(’-w4l and by an A.M.S. Postdoctoral Research Fellowship. I SIGNIFICANCE AND EXPLANATION The Korteweg - deVries equation (KdV for...decomposition of the solution resembling the use of Fourier transforms in solving constant coefficient equations . For the linearization about the zero...1.3) to eliminate (f 2)I(x,k), it is more convenient not to do so.) We prove the theorem by solving the equation - 4Q’ - 2Q’ + 4k 2 ’ for ’ and

  13. Aspects of Integrability in One and Several Dimensions,

    DTIC Science & Technology

    1986-01-01

    Korteweg - deVries (KdV) equation qt = q - 6qq x q = q(x,t), the recursion operator I is D 4q - 2q Dl. where 0 3x’ (D1 f)(x) f/xf( )dE. If 6 is the...70 It is also well known that the Harry-Dym 6 2 equation , can be mapped to a modified Korteweg - deVries (MKdV) equation via an extended...Petviashvili (a two dimensional analogue of the Korteweg - deVries ) and the Davey-Stewartson (a two dimensional analogue of the nonlinear Schr6dinger

  14. Photoprocesses in quinolone substituted

    NASA Astrophysics Data System (ADS)

    Vasilyeva, N. Y.; Vusovich, O. V.

    2002-03-01

    In the present work the analysis of the possible ways of energy degradation of electron excited states of 4-methyl-7- hydxyquinolone-2 (Q) and its protolytic species is presented (Figure 1); a ratio of radiative and nonradiative channels of deactivation of energy of electronic excitation is established; constants of photophysical processes (internal and intercrossing conversion), proceeding after act of absorption of light are designed. Study of exited state intramolecular proton transfer (ESIPT) in quinolones is interesting as a source of information on the relative importance of these processes in the photophysics and photochemistry of such molecular systems.

  15. Quaternion Utilization in a Missile Model

    DTIC Science & Technology

    1980-03-01

    8217^g^! l "^^’,^^S?ag!gBBH|M^BIB«aIji AFIT/GST/MA/80M-3 (is William jfyThorae f wcmngi Approved for public release; distribution unlimited...Eisenman, Richard L . Matrix Vector Analysis. New York: McGraw-Hill Book Company, Inc., 1963. 5. First Ann Arbor Corporation. Navy ACMR/I Missile...Xq3k . Also for X * -1 (- l )q = -qfl - qxi - q2J - q3k and q + t- l )q! - tq0-q£) + Cq^qfJi + Cq2-q£)j + Cq3-qJ)k . So, quaternions obey the

  16. Solution of the modified Helmholtz equation in a triangular domain and an application to diffusion-limited coalescence.

    PubMed

    ben-Avraham, D; Fokas, A S

    2001-07-01

    A new transform method for solving boundary value problems for linear and integrable nonlinear partial differential equations recently introduced in the literature is used here to obtain the solution of the modified Helmholtz equation q(xx)(x,y)+q(yy)(x,y)-4 beta(2)q(x,y)=0 in the triangular domain 0< or =x< or =L-y< or =L, with mixed boundary conditions. This solution is applied to the problem of diffusion-limited coalescence, A+A<==>A, in the segment (-L/2,L/2), with traps at the edges.

  17. The Generalized Variance of a Stationary Autoregressive Process

    DTIC Science & Technology

    1976-10-01

    random variables with ~vt = 0 , < 00 • The associated polynomial equation (17) Zq + ~ zq-l + + ~ = 0 ~l ... ~q has roots •.• ’ z • q Durbin (1959... algebraic methods to show (18) for n = p = q . As an example, these results for p = q = l are 2 Q = l/(1-S ) l l and I I 2T+2 2 2 N = (1-a )/(1-a...l/(1-a ) ~T l l l Durbin (1959) considered the case p = q = 2 in detail. as T~oo. For further discussion, see the recent paper by Shaman (1976

  18. The Effect of Turbulence Ingestion on Propeller Broadband Thrust

    DTIC Science & Technology

    1991-12-01

    unsteady force caused by turbulence ingestion has been studied by several investigators in the past. Most previous studies are based upon special...correlation method because it is the more direct approach and is easier to apply numerically. However, for completeness of the study , the spec- trum...p($RT)2]2(CR) 2U2/ (Q RT)2 2 (~- n(Y) q( ) _ I A,[(k 2 sin + c Cos -)b] 1 UT UTUT 0 2(k 2)dk2 where UT is the resultant tip speed VV 2 + (RTQ) 2 (V

  19. Joint Spectrum Allocation and Scheduling in Multi-Radio Multi-Channel Cognitive Radio Wireless Networks

    DTIC Science & Technology

    2010-04-01

    radios in node y. The time required to solve this problem can be significantly decreased if a greedy clique decomposition of the conflict graph is...performed. Specifically, a set of cliques © Qi, i = 1, 2, ...Q ª are found such that if yj ∈ χ (xk), then there is a clique Qi such that xk ∈ Qi and yj ∈ Qi...and trace files. The propagation simulator is based on ray -tracing and accounts for reflections off of the ground and off of buildings, transmission

  20. Co-occurrence of mutations in both dystrophin- and androgen-receptor genes is a novel cause of female Duchenne muscular dystrophy.

    PubMed

    Katayama, Yoshinori; Tran, Van Khanh; Hoan, Nguyen Thi; Zhang, Zhujun; Goji, Katsumi; Yagi, Mariko; Takeshima, Yasuhiro; Saiki, Kayoko; Nhan, Nguyen Thu; Matsuo, Masafumi

    2006-06-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder. Here, we report a novel mechanism for the occurrence of DMD in females. In a Vietnamese DMD girl, conventional PCR amplification analysis disclosed a deletion of exons 12-19 of the dystrophin gene on Xp21.2, with a karyotype of 46, XY. Furthermore, a novel mutation in the androgen-receptor gene on Xq11.2-q12 was identified in this girl, which led to male pseudohermaphroditism. Co-occurrence of mutations of these two genes constitutes a novel mechanism underlying female DMD.

  1. Nonlinear Stochastic Interaction in Aeroelastic Structures.

    DTIC Science & Technology

    1988-01-29

    Frangopol. D NI (1985ai Sensiti-ts of reltabiltIisbaed optimum de Boyce. W E (1966). Stochastic nonthomogeneous Sturm - Liouville problem. Strut, Dig 111. 1703...It is known that 4,2 =- qlql -q11+- q2 4j the result of any linear operator , with constant coefficients, , 1 = 3E,- - 2 q) applied to a random...Gaussian process results in a Gaussian k. - 3EIIP (2) process. However. if the operator is nonlinear, the resulting It is seen that the left-hand side of

  2. The algebra of supertraces for 2+1 super de Sitter gravity

    NASA Technical Reports Server (NTRS)

    Urrutia, L. F.; Waelbroeck, H.; Zertuche, F.

    1993-01-01

    The algebra of the observables for 2+1 super de Sitter gravity, for one genus of the spatial surface is calculated. The algebra turns out to be an infinite Lie algebra subject to non-linear constraints. The constraints are solved explicitly in terms of five independent complex supertraces. These variables are the true degrees of freedom of the system and their quantized algebra generates a new structure which is referred to as a 'central extension' of the quantum algebra SU(2)q.

  3. Generalization of the possible algebraic basis of q-triplets

    NASA Astrophysics Data System (ADS)

    Tsallis, Constantino

    2017-02-01

    The so called q-triplets were conjectured in 2004 [C. Tsallis, Physica A 340, 1 (2004)] and then found in nature in 2005 [L.F. Burlaga, A.F. Vinas, Physica A 356, 375 (2005)]. A relevant further step was achieved in 2005 [C. Tsallis, M. Gell-Mann, Y. Sato, PNAS 102, 15377 (2005)] when the possibility was advanced that they could reflect an entire infinite algebra based on combinations of the self-dual relations q → 2 - q (additive duality) and q → 1/q (multiplicative duality). The entire algebra collapses into the single fixed point q = 1, corresponding to the Boltzmann-Gibbs entropy and statistical mechanics. For q ≠ 1, an infinite set of indices q appears, corresponding in principle to an infinite number of physical properties of a given complex system describable in terms of the so called q-statistics. The basic idea that is put forward is that, for a given universality class of systems, a small number (typically one or two) of independent q indices exist, the infinite others being obtained from these few ones by simply using the relations of the algebra. The q-triplets appear to constitute a few central elements of the algebra. During the last decade, an impressive amount of q-triplets have been exhibited in analytical, computational, experimental and observational results in natural, artificial and social systems. Some of them do satisfy the available algebra constructed solely with the additive and multiplicative dualities, but some others seem to violate it. In the present work we generalize those two dualities with the hope that a wider set of systems can be handled within. The basis of the generalization is given by the selfdual relation q → qa(q) ≡ ((a+2)-aq) / (a-(a-2)q) (a ∈ R). We verify that qa(1) = 1, and that q2(q) = 2 - q and q0(q) = 1/q. To physically motivate this generalization, we briefly review illustrative applications of q

  4. Effects of ammonia on the structure of the oxygen-evolving complex in photosystem II as revealed by light-induced FTIR difference spectroscopy.

    PubMed

    Hou, Li-Hsiu; Wu, Chia-Ming; Huang, Hsin-Ho; Chu, Hsiu-An

    2011-11-01

    NH(3) is a structural analogue of substrate H(2)O and an inhibitor to the water oxidation reaction in photosystem II. To test whether or not NH(3) is able to replace substrate water molecules on the oxygen-evolving complex in photosystem II, we studied the effects of NH(3) on the high-frequency region (3750-3550 cm(-1)) of the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectra (pH 7.5 at 250 K), where OH stretch modes of weak hydrogen-bonded active water molecules occur. Our results showed that NH(3) did not replace the active water molecule on the oxygen-evolving complex that gave rise to the S(1) mode at ~3586 cm(-1) and the S(2) mode at ~3613 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) FTIR difference spectrum of PSII. In addition, our mid-frequency FTIR results showed a clear difference between pH 6.5 and 7.5 on the concentration dependence of the NH(4)Cl-induced upshift of the S(2) state carboxylate mode at 1365 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) spectra of NH(4)Cl-treated PSII samples. Our results provided strong evidence that NH(3) induced this upshift in the spectra of NH(4)Cl-treated PSII samples at 250 K. Moreover, our low-frequency FTIR results showed that the Mn-O-Mn cluster vibrational mode at 606 cm(-1) in the S(2)Q(A)(-)/S(1)Q(A) spectrum of the NaCl control PSII sample was diminished in those samples treated with NH(4)Cl. Our results suggest that NH(3) induced a significant alteration on the core structure of the Mn(4)CaO(5) cluster in PSII. The implication of our findings on the structure of the NH(3)-binding site on the OEC in PSII will be discussed.

  5. Two-electron reactions S2QB -->S0QB and S3QB -->S1QB are involved in deactivation of higher S states of the oxygen-evolving complex of Photosystem II.

    PubMed

    Antal, Taras K; Sarvikas, Päivi; Tyystjärvi, Esa

    2009-06-03

    The oxygen-evolving complex of Photosystem II cycles through five oxidation states (S(0)-S(4)), and dark incubation leads to 25% S(0) and 75% S(1). This distribution cannot be reached with charge recombination reactions between the higher S states and the electron acceptor Q(B)(-). We measured flash-induced oxygen evolution to understand how S(3) and S(2) are converted to lower S states when the electron required to reduce the manganese cluster does not come from Q(B)(-). Thylakoid samples preconditioned to make the concentration of the S(1) state 100% and to oxidize tyrosine Y(D) were illuminated by one or two laser preflashes, and flash-induced oxygen evolution sequences were recorded at various time intervals after the preflashes. The distribution of the S states was calculated from the flash-induced oxygen evolution pattern using an extended Kok model. The results suggest that S(2) and S(3) are converted to lower S states via recombination from S(2)Q(B)(-) and S(3)Q(B)(-) and by a slow change of the state of oxygen-evolving complex from S(3) and S(2) to S(1) and S(0) in reactions with unspecified electron donors. The slow pathway appears to contain two-electron routes, S(2)Q(B) -->S(0)Q(B), and S(3)Q(B) -->S(1)Q(B). The two-electron reactions dominate in intact thylakoid preparations in the absence of chemical additives. The two-electron reaction was replaced by a one-electron-per-step pathway, S(3)Q(B) -->S(2)Q(B) -->S(1)Q(B) in PS II-enriched membrane fragments and in thylakoids measured in the presence of artificial electron acceptors. A catalase effect suggested that H(2)O(2) acts as an electron donor for the reaction S(2)Q(B) -->S(0)Q(B) but added H(2)O(2) did not enhance this reaction.

  6. Seismic Discrimination

    DTIC Science & Technology

    1976-06-30

    M > 7.8 used to calculate the excitation of the S 21 Chandler wobble are taken from the catalog compiled by Duda and supplemented by informa...the pole in January 1901 and the frequency w0 and damping Q of the Chandler wobble . The synthetic wobble m(t)is computed from: m(t) = m(t0) exp[iw(t...t0)] + £ sfeH(t - tfc) • {l - (l + -^ ) exp [iw(t -tk)] where w is the complex circular frequency of the Chandler wobble : u = w0(l + i/2Q

  7. Small terminal deletions of the long arm of chromosome 2: Two new cases

    SciTech Connect

    Fisher, A.M.; Ellis, K.H.; Browne, C.E.; Barber, J.C.K.; Barker, M.; Kennedy, C.R.; Foley, H.; Patton, M.A.

    1994-12-01

    We report on 2 girls with small de novo terminal deletions of the long arm of chromosome 2 and breakpoints within q37. Four cases with similar or more extensive deletions have been previously reported in full. Hypotonia and psychomotor retardation were the only manifestations common to all 6 cases. The phenotype associated with small terminal 2q deletions is variable and clearly not always as mild as indicated in previous reports. The abnormality may also be more common than has been assumed. 12 refs., 3 figs., 1 tab.

  8. Lifetimes and configuration mixing in 110Cd

    NASA Astrophysics Data System (ADS)

    Lobach, Yu. N.; Efimov, A. D.; Pasternak, A. A.

    Lifetimes of excited states in 110Cd have been measured by the Doppler shift attenuation method in the reaction (α,2nγ) at Eα= 25 MeV. Lifetime values for 8 states and lifetime limits for 3 states were obtained. The band structures of 110Cd have been interpreted in terms of a modified version of the interacting boson model (IBM + 2 q.p.). The calculations explain well the excitation energies and electromagnetic transition probabilities up to Jπ= 16+, except for the 10+1 state. The structural features are discussed in terms of collective and two quasiparticle excitations.

  9. Recombinant chromosome 18 resulting from a maternal pericentric inversion

    SciTech Connect

    Ayukawa, Hiroshi; Tsukahara, Masato; Fukuda, Masamichi; Kondoh, Osamu

    1994-05-01

    We report on a newborn girl with duplication of 18q12.2{yields}18 qter and deficiency of 18p11.2{yields}18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18)(p11.2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion. 8 refs., 3 figs., 1 tab.

  10. X-Ray Crystal Structures of ((Me3SiCH2)2InCl)2 and ((Me3SiCH2)InCl2)

    DTIC Science & Technology

    1994-01-18

    Continue on reverse of necessary and identify by block number) FIELD GROUP SUB- GROUP synthesis, crystal structure, indium compounds 19. ABSTRACT (Continue...crystal X-ray analysis. Compound I crystallizes as a centrosymmetric dimer, [(Me 3SiCH 2)2 InCI]2 , in the triclinic space group P1 [(Cil), No.2] with unit...1.378 g cm-3 for Z = 1 [R = 0.072 (R. = 0.098)]. Compound II crystallizes as an infinite polymer, [(Me 3SiCH2 )InCI2q,, in the triclinic space group P1

  11. A Validation of the Spatial Variant of the Sternberg Memory Search Task: Search Rate, Response Hand, & Task Interference.

    DTIC Science & Technology

    1981-06-01

    COMPLETING FORM REPORT NUMBER 2. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER EPL-81-2/ONR-8I-2 q - 4 TITL.E (ard SubtIlet) S . TYPE OF REPORT & PERIOD COV...PERFORMINOO. REPORT NUMBER 7. AUTHOR(*) S , CONTRACT OR GRANT NUMBER(.J Christopher D. WickensDi ae SadrvN-O00-14-79-C-0658 Diane Sandry John/Mi calizzi 9...In experiment 1, the effect of memory set size (1, 2, and 4) on the slope of the IORM DD A 7 1473 o,T o, I NOV S 1 OBSOLETE Unclassified ’,N 107 L 01

  12. Study on the effect of the impeller and diffuser blade number on reactor coolant pump performances

    NASA Astrophysics Data System (ADS)

    Long, Y.; Yin, J. L.; Wang, D. Z.; Li, T. B.

    2016-05-01

    In this paper, CFD approach was employed to study how the blade number of impeller and diffuser influences reactor coolant pump performances. The three-dimensional pump internal flow channel was modelled by pro/E software, Reynolds-averaged Naiver-Stokes equations with the k-ε turbulence model were solved by the computational fluid dynamics software CFX. By post-processing on the numerical results, the performance curves of reactor coolant pump were obtained. The results are as follows, with the blade number of the impeller increasing, the head of the pump with different diffuser universally increases in the 8Q n∼1.2Q n conditions, and at different blade number of the diffuser, the head increases with the blade number of the impeller increasing. In 1.0Q n condition, when the blades number combination of impeller and diffuser chooses 4+16, 7+14 and 6+18, the head curves exist singular points. In 1.2Q n condition, the head curve still exists singular point in 6+18. With the blade number of the impeller increasing, the efficiency of the pump with different diffuser universally decreases in the 0.8Q n and 1.0Q n conditions, but in 1.2Q n condition, the efficiency of the pump with different diffuser universally increases. In 1.0Q n condition, the impellers of 4 and 5 blades are better. When the blade number combination of impeller and diffuser choose 4+11, 4+17, 4+18, 5+12, 5+17 and 5+18, the efficiencies relatively have higher values. With the blade number of the impeller increasing, the hydraulic shaft power of the pump with different diffuser universally increases in the 0.8Q n∼1.2Q n conditions, and with the blade number of the diffuser increasing, the power of different impeller overall has small fluctuation, but tends to be uniform. This means the increase of the diffuser blade number has less influence on shaft power.The influence on the head and flow by the matching relationship of the blades number between impeller and diffuser is very complicated, which

  13. Luminescence Study of Ion-Implanted and MBE-Grown Er-Doped GaAs and A1(x)Ga(1-x)As

    DTIC Science & Technology

    1993-03-01

    Semiconductors," Phys. Rev. B. 4E (3): 1423-1428 (July 1992). M . Salvi, H. L’Harridon, P. N. Favennec, D. Moutonne:, M . Gauneau, and M . Kechouane . "A...normal coordinates: H = M (p2 + M2w2q2), 0 2 where p = Mdu/dt and q = u = R - P,. The basic assumption of the CC diagram is that the effect of the electronic...also found two different processes involved in the temperature quenching of Yb3+. Klein (1988] fitted the PL intensity to an expression of the form I M

  14. Non-Equilibrium Radiation from Shock-Heated Air

    DTIC Science & Technology

    1991-07-01

    v- n 260nm LTER" vkT 4e_-. W 4 e IW- l watts (1) 2 (Q r)u cm3 sr cm - I r 0 I I .l I 1 I I I j 0 2 4 6 8 10 12 14 16 18 20 22 where CALCULATED ...Measurements, 210 nm 293 6 Radiation Measurements, 2 0 nm 30 7 Infrared Radiation Matrix, Experiment and Calculation 31 8 Three Temporal Parameters...Characterizing Non-equilibrium 32 I Infrared Radiation 9 Infrared Incubation Time, Experiment and Calculation 33 1 1 0 Infrared Time-To-Half-Peak

  15. Correlation between temperature variations of static and dynamic properties in glass-forming liquids

    SciTech Connect

    Voylov, D. N.; Griffin, P. J.; Mercado, B.; Keum, J. K.; Nakanishi, M.; Novikov, V. N.; Sokolov, A. P.

    2016-12-29

    In this detailed analysis of the static structure factor S(Q) in several glass-forming liquids we show that the temperature variations of the width of the main diffraction peak Q(T ) correlate with the fragility of these liquids. Our observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We also show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, lc 2 /Q, and the size of cooperatively rearranging regions.

  16. Retrodirective Noise-Correlating Radar in X-Band

    DTIC Science & Technology

    2007-11-02

    detection was occurring with a single pulse. Finally the radar was characterized on a target in motion: the same 30-caliber bullet pendulating on the...kite string in front of the RNC transceiver. The pendulating amplitude was roughly 4 inches and the pendulating axis was about 45o relative to the...Radiation reflected from a target can be t1 t3 t4 t6t5 t2 Q I Q I Fig.13. Target track of 30-caliber bullet at six successive times of pendulating

  17. Mechanism and site of inhibition of AMPA receptors: substitution of one and two methyl groups at the 4-aminophenyl ring of 2,3-benzodiazepine and implications in the "E" site.

    PubMed

    Wang, Congzhou; Wu, Andrew; Shen, Yu-Chuan; Ettari, Roberta; Grasso, Silvana; Niu, Li

    2015-08-19

    2,3-Benzodiazepines are a well-known group of compounds for their potential antagonism against AMPA receptors. It has been previously reported that the inhibitory effect of 2,3-benzodiazepine derivatives with a 7,8-ethylenedioxy moiety can be enhanced by simply adding a chlorine atom at position 3 of the 4-aminophenyl ring. Here we report that adding a methyl group at position 3 on the 4-aminophenyl ring, termed as BDZ-11-7, can similarly enhance the inhibitory activity, as compared with the unsubstituted one or BDZ-11-2. Our kinetic studies have shown that BDZ-11-7 is a noncompetitive antagonist of GluA2Q homomeric receptors and prefers to inhibit the closed-channel state. However, adding another methyl group at position 5 on the 4-aminophenyl ring, termed as BDZ-11-6, fails to yield extra inhibition on GluA2Q receptors. Instead, BDZ-11-6 exhibits a diminished inhibition of GluA2Q. Site interaction test indicates the two compounds, BDZ-11-6 and BDZ-11-7, bind to the same site on GluA2Q, which is also the binding site for their prototype, BDZ-11-2. Based on the results from this and our earlier studies, we propose that the binding site that accommodates the 4-aminophenyl ring must contain two interactive points, with one preferring polar groups like chlorine and the other preferring nonpolar groups such as a methyl group. Either adding a chlorine or a methyl group may enhance the inhibitory activity of 2,3-benzodiazepine derivatives with a 7,8-ethylenedioxy moiety. Adding any two of the same group on positions 3 and 5 of the 4-aminophenyl ring, however, significantly reduces the interaction between these 2,3-benzodiazepines and their binding site, because one group is always repelled by one interactive point. We predict therefore that adding a chlorine atom at position 3 and a methyl group at position 5 of the 4-aminophenyl ring of 2,3-benzodiazepine derivatives with a 7,8-ethylenedioxy moiety may produce a new compound that is more potent.

  18. Demodulation Processes in Auditory Perception.

    DTIC Science & Technology

    1992-08-15

    choice procedure (2-0. 2AFC ) was used to determine step/glide discrimination performance. In each trial a stimulus was presented in each of four...rise/fall signal-tracking (perhaps rate-place coding) has a longer time time) were presented at 35 dB SL in the same 2-0, 2AFC constant than the phase...signal and the STEP signal were just discriminable (75% correct in 2Q, 2AFC ) we assumed that the I duration of a single step was less than the width of

  19. A case of partial trisomy 20p resulting from meiotic recombination of a maternal pericentric inversion.

    PubMed

    Kang, Jeong-Eun; Park, Mi Young; Cheon, Chong Kun; Lee, Hyoung Doo; Hwang, Sang-Hyun; Yi, Jongyoun

    2012-01-01

    Here we report the cytogenetic and clinical manifestations observed in a patient with a rec(20)dup(20p)inv(20)(p11.2q13.3)mat. The patient was a full-term newborn girl with asymmetric intrauterine growth restriction and multiple congenital malformations, including a ventricular septal defect, pulmonary atresia, ambiguous genitalia, clinodactyly, and sacral dimpling. To our knowledge, this is the 4th report in the world and the 1st one in Korea of a patient with rec(20)dup(20p).

  20. The International Conference on Hemorrhagic Fever with Renal Syndrome (1st) Held in Seoul, Korea on 4-6 May 1989

    DTIC Science & Technology

    1990-05-01

    3, kA. M. tAV MtA~ FC4.12 L2-Q0 psmamto ~ o ofavl eblood s~fw rhang bi eptdanlic ltcmonfvcl- t~Lh~ttd.W. I Iut gltui CM Il~~i ~ I~.C~hJ~ t. S i M-13...Considering numerous population of spe- cies and level of infections,mammals had important place in epizootic process . Serological confirmation and virus...vaccinia virus, at the meantime, the normal morphogenetic process of vaccinia virus was evidently visiulized. * donated by Dr. C.S.Schmaljohn 36 A

  1. Recommended Alternate Qualification Courses for the M16 Rifle

    DTIC Science & Technology

    1987-06-01

    Services AREA & WORK U71T NUMBERS Litton Systems, Inc. 2Q263743A794M P.O. Box 7113, Mountai.n View, CA 94039-7113 322(:2 II. CONTROLLING OFFICE NAME AND...Record Fire and the KDAC require soldiers to apply the tour fundamentals of marksmanship (steady position, trigger squeeze, breath control , and...34, Thet Alteraste Ceurse wI be used only when standard rccrdW Miread Knamt Dsim V441a14% rerge are unsira ,Iee "thadfris tee 2 m ew "ar. e ~tltnet Prior

  2. Dissecting and Targeting Latent Metastasis

    DTIC Science & Technology

    2014-09-01

    National Academy of Sciences of the United States of America 100, 3983-3988 (2003). 9. J. Holash, P. C. Maisonpierre, D. Compton , P. Boland, C. R...80 00 00 D E Click # QC20111130154029 Wed, Nov 30, 2011 15:40:32 Em filter=Open Bin:M (8), FOV12.8, f1, 10s Camera : IS0702N4087, Spectral Instruments...did not trigger apoptosis (Figure S2Q). These results suggested that plasmin acting through unknown substrates kills infiltrating cancer cells in the

  3. Targeted Basic Studies of Ferroelectric and Ferroelastic Materials for Piezoelectric Transducer Applications.

    DTIC Science & Technology

    1980-12-01

    S. Nomura (1980) . J. Solid State Chem. 35 (in press). Beattie , A. G. and C. A. Samara (1971). J. Appl. Phys. 42, 2376. Cross, L. E., S. J. Jang, R...P2 -2_ - l/2xrp2 + Qp(P +r + 2 , ) (2) .---.- A~.- F A 4 The dielectric and elastic equations of state follow as 2 4A = PA[a.+ + 2Q(1 + /)p + 2...tetragonal, rhombohedral, and orthorhombic states are given by a set of equations similar to those given in Section 2. Choosing an arbitrary value and

  4. Quasi-stationary parameters of small bodies in the solar system

    NASA Astrophysics Data System (ADS)

    Kramer, E. N.; Shestaka, I. S.

    1987-03-01

    The following quasistationary parameters of small bodies in the solar system are introduced: P = 0.6/a-[a(1-e2)]cos2i-2, Q = 0.4+(2a-1)(1-e2)cos2i- e2(0.4-sin2ωmsin2i). These are investigated on the basis of data of photographic and radar observations of meteors, comets and Apollo-Amor asteroids. From the quasistationary parameters P and Q one can infer the genetic relations between the bodies studied, specify the probabilities of their encounters with planets and the meteor matter influx on the planets of our solar system.

  5. From decay to complete breaking: pulling the strings in SU(2) Yang-Mills theory.

    PubMed

    Pepe, M; Wiese, U-J

    2009-05-15

    We study {2Q+1} strings connecting two static charges Q in (2+1)D SU(2) Yang-Mills theory. While the fundamental {2} string between two charges Q=1/2 is unbreakable, the adjoint {3} string connecting two charges Q=1 can break. When a {4} string is stretched beyond a critical length, it decays into a {2} string by gluon pair creation. When a {5} string is stretched, it first decays into a {3} string, which eventually breaks completely. The energy of the screened charges at the ends of a string is well described by a phenomenological constituent gluon model.

  6. Evaluation of Quasi-Linear Diffusion Coefficients for Whistler Mode Waves in a Plasma with Arbitrary Density Ratio

    DTIC Science & Technology

    2005-03-22

    Refraction Since sin 2 Ogm < sin 2 0r, < 1, the separating curve crosses [12] The standard wave coefficients [Stix, 1962] for a cold zero at w, with...o/ slwa ,tehg-est 00 "q *Mk= *peak=*okK 6.37x10 6.37x10 7.08x 10-’ 0 Qgm Q./2 1)..0 ogm fne/2 Q.. 0 ogm 0.2. Figure 4. The function A11(w) (dashed

  7. Inclusive Measurements of Inelastic Scattering on unpolarized H and D targets at 27.6 GeV

    SciTech Connect

    De Nardo, Lara

    2011-07-15

    Measurements of the inclusive proton and deuteron structure functions F{sub 2}{sup p} and F{sub 2}{sup d} are presented. The data cover the ranges 0.006{<=}x{<=}0.9 and 0.1 GeV{sup 2}{<=}Q{sup 2}{<=}20 GeV{sup 2} and are in agreement with existing world data in the region of overlap. The measured cross sections were used, in combination with available world data, to perform fits to the total photon-proton cross section.

  8. Electron-Nuclear Dynamics in a Quantum Dot under Nonunitary Electron Control

    DTIC Science & Technology

    2011-07-20

    Þ sin2 ! eTR 2 ; (8) where Se is the length of the electron steady-state SV and for brevity we have suppressed the superscript 1 [13]. The zero...of m such that ð!e þmAÞTR is an odd integer multiple of , and the locations of these peaks can be controlled by adjusting ! eTR . A systematic...q20 2q0 cos; ð1 q20Þ tanð! eTR =2Þ; q0! eTR sin; (11) where c is as in Ref. [15]. Nonzero x; y components arise from expanding the Overhauser

  9. Electron-capture collisions at keV energies of multiply charged ions of carbon and argon with molecular deuterium

    SciTech Connect

    Bliman, S.; Aubert, J.; Geller, R.; Jacquot, B.; Van Houtte, D.

    1981-04-01

    Single- and double-electron-capture cross sections have been measured for C/sup q/+ with initial charges 2 < or = q < or = 6 and for Ar/sup q/+ with initial charges 2 < or = q < or = 12 incident on molecular deuterium gas targets. The cross sections show little dependence on the incident-ion energy for the range studied 2q to 10q keV. The single-electron-capture cross sections do not vary monotonically with the initial charge, but show an oscillation about a mean curve, reflecting the projectile electronic structure.

  10. Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

    DTIC Science & Technology

    2013-04-01

    with both maternal and paternal triplications associated with poor outcome. Clinical studies indicate that most individuals diag- nosed with dup(15...1979;50:259Y70 13. Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q...cases with dup(15)(q11.2-q12): One of maternal and one of paternal origin. Genet Med 2000;2:131Y35 19. Bolton PF, Veltman MWM, Weisblatt E, et al

  11. Quantum symmetries induced by phonons in the Hubbard model

    NASA Astrophysics Data System (ADS)

    Montorsi, Arianna; Rasetti, Mario

    1994-03-01

    We show how the addition of a phonon field to the Hubbard model deforms the superconducting su(2) part of the global symmetry Lie algebra su(2)⊗su(2)/openZ2, holding at half filling for the customary model, into a quantum [su(2)]q symmetry, holding for a filling which depends on the electron-phonon interaction strength. Such symmetry originates in the feature that in the presence of phonons the hopping amplitude turns out to depend on the coupling strength. The states generated by resorting to this q symmetry exhibit both off-diagonal long-range order and pairing.

  12. An Experimental Investigation of Wall Pressure Fluctuations Beneath Non- Equilibrium Turbulent Flows

    DTIC Science & Technology

    1986-05-01

    J.S. and Plersol, A.G., Engineering Applications of Correlation and Spectral Analyisis , Wiley-Intersclerice, New York (1980). Bhattacharjee, S...2 (ý) + K2 .COS 2 (p) -K )-SIN(, O) F = (1-K2)-SIN2 (q).SIN(E). 206 U The angles * and 0 are the azimuthal and polar angles, respectively, in3...spherical coordinates with tfle wire axis prescribing the polar axis. With the assumptions, U U0 + U’ V "V W -w and Ue U em+ U equation (A.2) can be

  13. Phase-Locked Semiconductor Quantum Well Laser Arrays.

    DTIC Science & Technology

    1987-03-01

    occupation by the carriers by solving the Schr ~ dinger wave equation . The Hamiltonian (in the single 1’ particle approximation) that is used in this...z, y, z) with respect to z in comparison to the other terms. Eq. (4.41) has the form of the time - dependent Schr6dinger equation in two dimensions...where z plays the role of time [811. The solution to this equation has the form (Z’, Z) = exp I P(z) + -TrI21 (4.42) + 2q(z) i4 V. CHAPTER 4. PHASE

  14. Inverse Problems and a Unified Approach to Integrability in 1, 1+1 and 2+1 Dimensions,

    DTIC Science & Technology

    1986-01-01

    PROBLEMS IN 2+1 w-, Let us consider the Davey-Stewartson equation (a two dimensional ana- logue of the nonlinear Schr ~ dinger equation ) . J. 1 2 2 2Q 2... depends on appropriate inverse data T(zR,zlfm 2 ..... Mn), zRc]Rn, zi]R,. m C R. T satisfies --hf==._T .Using this equation and introducing Born variables...Schro- p dinger equation one can reconstruct the potential in closed form, here one can only reduce the general problem to one for 2 x 2 matrices in

  15. Summary of Meteorological Observations, Surface (SMOS), Quantico, Virginia.

    DTIC Science & Technology

    1984-08-01

    69*06. 6. 6.no. * 1 07 & 37577 7r1r, ?4340 lt615$t 911169 4202 36q,? 5.1 Itb *2 q2. 411110 T riyr 17 1 5101 0T IM7 lt5T 17 SY.3 11 1175.1 Z 3101 iamB...8217 It. I.IS i±1L e Wosb~~b 1 1’S *oilZ , .1 i* 411110 ".LIITIZ!I~ DOW Point r jj j46 40 1 11111 A’ ’A ~. - PSYCHROMETRIC SUMMARY STATION STATIO "U at

  16. User’s Manual for the Screen Program.

    DTIC Science & Technology

    1980-05-01

    g3iveni part of the sensor coverage1 region (minuites). lnerto _~ The c;e n sor interation ti -I ( mi nuit es) . e~ta1Lu~av1iLt_ Prohahility that sensor is...the SSN thro it mills ah)reast of thp .i314 escorts. SIL1L1eT AODF (+hELP GIVES LIST): 15F2Q ENPFQ AlE PRW~vqAM TIME STE-P: 15 51:--;:(T MGD)F VIELP

  17. Identity-by-descent approaches identify regions of importance for genetic susceptibility to hereditary esophageal squamous cell carcinoma.

    PubMed

    Ko, Josephine My; Zhang, Peng; Law, Simon; Fan, Yanhui; Song, You-Qiang; Zhao, Xue Ke; Wong, Elibe H W; Tang, Sa; Song, Xin; Lung, Maria Li; Wang, Li Dong

    2014-08-01

    Worldwide, the highest prevalence of esophageal cancer (EC) occurs in Northern China. High-density SNP arrays allow identification of identity-by-descent (IBD) segments in genomic DNAs representative of shared common ancestral regions. We utilized IBD approaches to map susceptibility loci associated with low-penetrance SNPs in high-risk Henan hereditary esophageal squamous cell carcinoma (ESCC) patients. Affymetrix GeneChip Human mapping SNP array IBD analysis was performed in 32 Henan family history-positive (FH+) ESCC patients, 18 Henan healthy unrelated individuals, and 45 Chinese individuals from a CHB HapMap dataset using PLink (scoring IBD segments individually) and Beagle (scoring of shared IBD segments among case/case vs. control/control pairs) software. Both analyses identified longer IBD segment lengths associated with FH+ ESCC compared to controls. However, there was no strong evidence for a genetic founder effect. Pairing IBD analysis with BEAGLE identified 8 critical IBD segments residing at 2q32.1-q32.2, 3p22.3-p22.2, 4q21.1-q21.21, 7p22.2, 8q23.2-q23.3, 10q23.33-q24.1, 14q24.3 and 16q11.2-q12.1, which were more significantly shared among case/case compared to control/control. The shared IBD segments in FH+ ESCC samples with no overlap with control/CHB Hapmap may encompass potential cancer susceptibility loci. Selected targeted genes, PLCE1, GPT2, SIAH1 and CYP2C-18, residing within the IBD segments at 10q23.33-q24.1 and 16q11.2-q12.1, had statistically significant differential expression in primary ESCC tissues and are likely involved in ESCC carcinogenesis. The importance of these IBD segments to the etiology and development of ESCC in high-risk areas requires further study with expanded sample sizes. This is the first report employing the pairing IBD approach for elucidation of the genetic basis of hereditary ESCC in Henan by applying high throughput SNP array analysis.

  18. A Comparison of Innovative Training Techniques at the Defense Language Institute Foreign Language Center

    DTIC Science & Technology

    1986-06-01

    Considering how I studied Russian, I can honestly say that I.... a. did as much work as the next person b. will pass on the basis of sheer luck or...intelligence, because I did very little work c. worked very hard to learn Russian d. [Not applicable--we were not required to study outside of class.] 49. If my...ELEMENT. PROJECT, TASK U.S. Army Research Institute Field Unit at the AREA & WORK UNIT NUMBERS Presidio of Monterey 2Q263743A794 PO Box 5787, Presidio of

  19. A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter.

    PubMed Central

    Ghosh, S; Hauser, E R; Magnuson, V L; Valle, T; Ally, D S; Karanjawala, Z E; Rayman, J B; Knapp, J I; Musick, A; Tannenbaum, J; Te, C; Eldridge, W; Shapiro, S; Musick, T; Martin, C; So, A; Witt, A; Harvan, J B; Watanabe, R M; Hagopian, W; Eriksson, J; Nylund, S J; Kohtamaki, K; Tuomilehto-Wolf, E; Boehnke, M

    1998-01-01

    In the first reported positive result from a genome scan for non-insulin-dependent diabetes mellitus (NIDDM), Hanis et al. found significant evidence of linkage for NIDDM on chromosome 2q37 and named the putative disease locus NIDDM1 (Hanis et al. 1996. Nat. Genet. 13:161-166). Their total sample was comprised of 440 Mexican-American affected sib-pairs from 246 sibships. The strongest evidence for linkage was at marker D2S125 and best estimates of lambdas (risk to siblings of probands/population prevalence) using this marker were 1.37 under an additive model and 1.36 under a multiplicative model. We examined this chromosomal region using linkage analysis in a Finnish sample comprised of 709 affected sib-pairs from 472 sibships. We excluded this region in our sample (multipoint logarithm of odds score /= 1.37. We discuss possible reasons why linkage to 2q37 was not found and conclude that this region is unlikely to be playing a major role in NIDDM susceptibility in the Finnish Caucasian population. PMID:9710438

  20. Resummation of transverse momentum distributions in distribution space

    NASA Astrophysics Data System (ADS)

    Ebert, Markus A.; Tackmann, Frank J.

    2017-02-01

    Differential spectra in observables that resolve additional soft or collinear QCD emissions exhibit Sudakov double logarithms in the form of logarithmic plus distributions. Important examples are the total transverse momentum q T in color-singlet production, N -jettiness (with thrust or beam thrust as special cases), but also jet mass and more complicated jet substructure observables. The all-order logarithmic structure of such distributions is often fully encoded in differential equations, so-called (renormalization group) evolution equations. We introduce a well-defined technique of distributional scale setting, which allows one to treat logarithmic plus distributions like ordinary logarithms when solving these differential equations. In particular, this allows one (through canonical scale choices) to minimize logarithmic contributions in the boundary terms of the solution, and to obtain the full distributional logarithmic structure from the solution's evolution kernel directly in distribution space. We apply this technique to the q T distribution, where the two-dimensional nature of convolutions leads to additional difficulties (compared to one-dimensional cases like thrust), and for which the resummation in distribution (or momentum) space has been a long-standing open question. For the first time, we show how to perform the RG evolution fully in momentum space, thereby directly resumming the logarithms [ln n ( q T 2 / Q 2)/ q T 2 ]+ appearing in the physical q T distribution. The resummation accuracy is then solely determined by the perturbative expansion of the associated anomalous dimensions.

  1. Genetic aspects of preeclampsia and the HELLP syndrome.

    PubMed

    Haram, Kjell; Mortensen, Jan Helge; Nagy, Bálint

    2014-01-01

    Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the -670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.

  2. Twisted hierarchies associated with the generalized sine-Gordon equation

    NASA Astrophysics Data System (ADS)

    Ma, Hui; Wu, Derchyi

    2011-09-01

    Twisted U- and twisted U/K-hierarchies are soliton hierarchies introduced by Terng to find higher flows of the generalized sine-Gordon equation. Twisted O(J,J)/O(J)× O(J)-hierarchies are among the most important classes of twisted hierarchies. In this paper, we derive explicit interesting first and higher flows of twisted O(J,J)/O(J)× O(J)-hierarchies, justify that the one-dimensional systems of twisted O(J,J)/O(J)× O(J)-hierarchies for J = Iq, n - q(1 ⩽ q ⩽ n - 1), called the generalized sinh-Gordon equations, are the Gauss-Codazzi equations for n-dimensional timelike submanifolds with constant sectional curvature 1 and index q in pseudo-Euclidean (2n - 1)-dimensional space {R}^{2n-1}_{2q-1} with index 2q - 1. Furthermore, a unified treatment of the inverse scattering theory for twisted O(J,J)/O(J)× O(J)-hierarchies is provided.

  3. Copy number gain at 12q12-14 may be important in the transformation from follicular lymphoma to diffuse large B cell lymphoma

    PubMed Central

    Hough, R E; Goepel, J R; Alcock, H E; Hancock, B W; Lorigan, P C; Hammond, D W

    2001-01-01

    The purpose of this study was to identify novel areas of genomic copy number change associated with transformation from follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBL). DNA was extracted from tumour cells micro-dissected from paraffin- embedded tissue sections in 24 patients with FL and subsequent transformation to DLBL and 18 patients with de novo DLBL. Tumour DNA was compared to reference DNA using comparative genomic hybridization. Abnormalities common to all 3 groups were gains on chromosomes 4q, 5q, 7q, 11q and X and losses on 3p, 8p and 10q. Copy number changes seen in both transformed and de novo DLBL and not seen in FL were gains on 2p and losses on 1q, 15q and Xq. Gains on 2q, 6p, 7p and 17q and losses on 5p and 8q were specific to transformed DLBL cases. Gain on 12q12-14 was found in 52% of the transformed DLBL cases and was never seen in its follicular counterpart. Patterns of genomic copy number change associated with specific clinical events in NHL have been demonstrated and suggest that gains on 2q, 6p, 7p, 12q and 17q and losses on 5p and 8q may be important in the transformation from low to high-grade disease. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11207045

  4. Model for the {Delta}(1600) resonance and {gamma}N{yields}{Delta}(1600) transition

    SciTech Connect

    Ramalho, G.; Tsushima, K.

    2010-10-01

    A covariant spectator constituent quark model is applied to study the {gamma}N{yields}{Delta}(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the {Delta}(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming {Delta}(1600) as the first radial excitation of {Delta}(1232), the pion cloud contributions are estimated based on an analogy with the {gamma}N{yields}{Delta}(1232) transition. To estimate the pion cloud contributions in the {gamma}N{yields}{Delta}(1600) transition, we include the relevant intermediate states, {pi}N, {pi}{Delta}, {pi}N(1440) and {pi}{Delta}(1600). Dependence on the four-momentum transfer squared, Q{sup 2}, is predicted for the magnetic dipole transition form factor, G{sub M}*(Q{sup 2}), as well as the helicity amplitudes, A{sub 1/2}(Q{sup 2}) and A{sub 3/2}(Q{sup 2}). The results at Q{sup 2}=0 are compared with the existing data.

  5. A model for the Delta(1600) resonance and gamma N -> Delta(1600) transition

    SciTech Connect

    G. Ramalho, K. Tsushima

    2010-10-01

    A covariant spectator constituent quark model is applied to study the gamma N -> Delta(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the Delta(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming Delta(1600) as the first radial excitation of Delta(1232), the pion cloud contributions are estimated based on an analogy with the gamma N -> Delta(1232) transition. To estimate the pion cloud contributions in the gamma N -> Delta(1600) transition, we include the relevant intermediate states, pi-N, pi-Delta, pi-N(1440) and pi-Delta(1600). Dependence on the four-momentum transfer squared, Q2, is predicted for the magnetic dipole transition form factor, GM*(Q2), as well as the helicity amplitudes, A_1/2(Q2) and A_3/2(Q2). The results at Q2=0 are compared with the existing data.

  6. Web-based Peer-Driven Chain Referrals for Smoking Cessation

    PubMed Central

    Sadasivam, Rajani S.; Cutrona, Sarah L.; Volz, Erik; Rao, Sowmya R.; Houston, Thomas K.

    2015-01-01

    Background We are testing web-based respondent-driven sampling (RDS) chain referrals to recruit smokers to the Decide2Quit.org (D2Q) web-assisted tobacco intervention. Methods Using an online survey of smokers, we assessed the potential of recruiting 1200 smokers in 9 months using RDS chain referrals. RDS is a complex sample design, and many factors can influence its success. We conducted simulations to determine the design of optimal RDS chains. Results Smokers (n=48) were mostly female (72%) and between ages 30–60 (82%). Estimation of smokers in their network: 1–5 (40%), 6–10 (24%), and 10–20 (22%), with mean number of intimate family (2.2, SD=2.1) and close friend smokers (3.7, SD=3.8). Most smokers (82%) were willing to refer to D2Q and thought their friends (mean=5.0, SD=4.4, range=0–20) would be open to referral. Simulations suggested that with a quota of 3 and 10 seeds, 99.9% of the sample would be achieved in 107 days if the acceptance probability was 0.5. Acceptance probability of 25% would necessitate an increased quota. Conclusions Our study suggests that it is possible to recruit smokers using RDS. PMID:23920576

  7. Interstitial deletions of chromosome 6q: genotype-phenotype correlation utilizing array CGH.

    PubMed

    Klein, O D; Cotter, P D; Moore, M W; Zanko, A; Gilats, M; Epstein, C J; Conte, F; Rauen, K A

    2007-03-01

    Interstitial deletions of the long arm of chromosome 6 are relatively rare, with fewer than 100 cases reported. Phenotypic variation is in large part due to differences in size and location of the segmental aneuploidy. We report three new patients with interstitial deletions of chromosome 6q defined at the molecular level by array comparative genomic hybridization (array CGH). In two of three cases, the molecular breakpoints differed from those indicated by conventional karyotyping, demonstrating the enhanced resolution of array CGH. Two patients had minimal deletions of 6 and 8.8 Mb involving 6q16.2-->q21, and the third patient had a deletion of 11.3 Mb spanning 6q15-->q21. All three had developmental delay, craniofacial dysmorphology, and functional eye disorders, suggesting that genes affecting brain and craniofacial development are located in 6q16.2-->q21, the deleted region common to all three patients. Furthermore, gene(s) for discordant phenotypic features, such as central diabetes insipidus, may reside at 6q15, the monosomic region unique to patient 3. All three cases described here showed loss of paternal alleles within the deleted segment, providing further evidence of the predominantly paternal origin for 6q deletions and rearrangements.

  8. Steric effect for proton, hydrogen-atom, and hydride transfer reactions with geometric isomers of NADH-model ruthenium complexes.

    PubMed

    Cohen, Brian W; Polyansky, Dmitry E; Achord, Patrick; Cabelli, Diane; Muckerman, James T; Tanaka, Koji; Thummel, Randolph P; Zong, Ruifa; Fujita, Etsuko

    2012-01-01

    Two isomers, [Ru(1)]2+ (Ru = Ru(bpy)2, bpy = 2,2'-bipyridine, 1 = 2-(pyrid-2'-yl)-1-azaacridine) and [Ru(2)]2+ (2 = 3-(pyrid-2'-yl)-4-azaacridine), are bioinspired model compounds containing the nicotinamide functionality and can serve as precursors for the photogeneration of C-H hydrides for studying reactions pertinent to the photochemical reduction of metal-C1 complexes and/or carbon dioxide. While it has been shown that the structural differences between the azaacridine ligands of [Ru(1)]2+ and [Ru(2)]2+ have a significant effect on the mechanism of formation of the hydride donors, [Ru(1HH)]2+ and [Ru(2HH)]2+, in aqueous solution, we describe the steric implications for proton, net-hydrogen-atom and net-hydride transfer reactions in this work. Protonation of [Ru(2*-)] in aprotic and even protic media is slow compared to that of [Ru(1*-)]+. The net hydrogen-atom transfer between *[Ru(1)]2+ and hydroquinone (H2Q) proceeds by one-step EPT, rather than stepwise electron-proton transfer. Such a reaction was not observed for *[Ru(2)]2+ because the non-coordinated N atom is not easily available for an interaction with H2Q. Finally, the rate of the net hydride ion transfer from [Ru(1HH)]2+ to [Ph3C]+ is significantly slower than that of [Ru (2HH)]2+ owing to steric congestion at the donor site.

  9. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity.

    PubMed

    Wang, Juexin; Shen, Dingding; Xia, Geqing; Shen, Wangzhen; Macdonald, Robert L; Xu, Dong; Kang, Jing-Qiong

    2016-10-20

    Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities. Structural modeling and structure-based analysis indicated that the surface of the wild-type γ2 subunit was naturally hydrophobic, which is suitable to be buried in the cell membrane. Different mutant γ2 subunits had different stabilities and different interactions with their wild-type subunit binding partners because they adopted different conformations and had different surface hydrophobicities and different tendency to dimerize. We utilized flow cytometry and biochemical approaches in combination with lifted whole cell patch-clamp recordings. We demonstrated that the truncated subunits had no to minimal surface expression and unchanged or reduced surface expression of wild-type partnering subunits. The amplitudes of GABA-evoked currents from the mutant α1β2γ2(R136*), α1β2γ2(Q390*) and α1β2γ2(W429*) receptors were reduced compared to the currents from α1β2γ2 receptors but with differentially reduced levels. This thus suggests differential protein structure disturbances are correlated with disease severity.

  10. Relation between minimum-error discrimination and optimum unambiguous discrimination

    SciTech Connect

    Qiu Daowen; Li Lvjun

    2010-09-15

    In this paper, we investigate the relationship between the minimum-error probability Q{sub E} of ambiguous discrimination and the optimal inconclusive probability Q{sub U} of unambiguous discrimination. It is known that for discriminating two states, the inequality Q{sub U{>=}}2Q{sub E} has been proved in the literature. The main technical results are as follows: (1) We show that, for discriminating more than two states, Q{sub U{>=}}2Q{sub E} may not hold again, but the infimum of Q{sub U}/Q{sub E} is 1, and there is no supremum of Q{sub U}/Q{sub E}, which implies that the failure probabilities of the two schemes for discriminating some states may be narrowly or widely gapped. (2) We derive two concrete formulas of the minimum-error probability Q{sub E} and the optimal inconclusive probability Q{sub U}, respectively, for ambiguous discrimination and unambiguous discrimination among arbitrary m simultaneously diagonalizable mixed quantum states with given prior probabilities. In addition, we show that Q{sub E} and Q{sub U} satisfy the relationship that Q{sub U{>=}}(m/m-1)Q{sub E}.

  11. Understanding of Nuclear Quadruple Interaction of ^ 19F* and Binding Energies of Solid Fluorine at the First-Principles Level

    NASA Astrophysics Data System (ADS)

    Mishra, D. R.; Aryal, M. M.; Adhikari, N. P.; Badu, S. R.; Pink, R. H.; Scheicher, R. H.; Chow, Lee; Das, T. P.

    2009-03-01

    We have studied the binding energy (BE) and nuclear quadrupole interaction (NQI) parameters for the ^19F* excited nuclear state in solid fluorine as part of our investigation [1] of the properties of solid halogens using the first principles Hartree-Fock Cluster procedure combined with many-body perturbation theory (MBPT), implemented by the Gaussian 03 set of programs. Our results show that Van der Waals interaction obtained from intermolecular electron correlation has dominant effect on the BE but negligible effect on the NQI parameters. For the latter, our e^2qQ is 117.7MHz forQ(^19F*), 0.072 *10-28 m^2 [2] and η is essentially zero.. The influence of vibrational effects on e^2qQ is being investigated using a first-principles procedure [3] to bridge the small remaining difference with experiment. [1] M.M. Aryal et al., Hyperfine Interact, 176, 51 (2007). [2] K.C.Mishra et al.,Phys. Rev.B25, 3389(1982). [3] N. Sahoo et al. Phys. Rev. Lett. 50, 913(1983) [4] H. Barfuss et al., Phys. Lett. 90A, 33(1982).

  12. On fractional Schro{sup ¨}dinger equation in R{sup N} with critical growth

    SciTech Connect

    Shang, Xudong E-mail: yynjnu@126.com; Zhang, Jihui; Yang, Yang E-mail: yynjnu@126.com

    2013-12-15

    In this paper, we study the following nonlinear fractional Schro{sup ¨}dinger equation with critical exponent h{sup 2α}(−Δ){sup α}u+V(x)u=|u|{sup 2{sub α}{sup *−2}}u+λ|u|{sup q−2}u,x∈R{sup N}, where h is a small positive parameter, 0 < α < 1, 2<q<2{sub α}{sup *}, 2{sub α}{sup *}=(2N)/(N−2α) is the critical Sobolev exponent, and N > 2α, λ > 0 is a parameter. The potential V:R{sup N}→R is a positive continuous function satisfying some natural assumptions. By using variational methods, we obtain the existence of solutions in the following case: if 2<q<2{sub α}{sup *}, there exists λ{sub 0} > 0 such that for all λ ⩾ λ{sub 0}, we show that it has one nontrivial solution and there exist at least cat{sub Λ{sub δ}}(Λ) nontrivial solutions; if max(2,(4α)/(N−2α) ) 0.

  13. Identification, expression, and immuno-reactivity of Sol i 2 & Sol i 4 venom proteins of queen red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae).

    PubMed

    Lockwood, Stephanie A; Haghipour-Peasley, Jilla; Hoffman, Donald R; Deslippe, Richard J

    2012-10-01

    We report on two low-molecular weight proteins that are stored in the venom of queen red imported fire ants (Solenopsis invicta). Translated amino acid sequences identified one protein to have 74.8% identity with the Sol i 2w worker allergen, and the other protein was found to have 96/97% identity with Sol i 4.01w/4.02w worker allergens. Both Sol i 2 and Sol i 4 queen and worker proteins were expressed using pEXP1-DEST vector in SHuffle™ T7 Express lysY Escherichia coli. Proteins were expressed at significant concentrations, as opposed to the μg/ml amounts by our previous expression methods, enabling further study of these proteins. Sol i 2q protein bound weakly to human IgE, sera pooled from allergic patients, whereas Sol i 2w, Sol i 4.01w, and Sol i 4q proteins bound strongly. Despite Sol i 2w and Sol i 2q proteins having 74.8% identity, the queen protein is less immuno-reactive than the worker allergen. This finding is consistent with allergic individuals being less sensitive to queen than worker venom.

  14. Measurement of the cross section ratio σψ(2S)/σJ/ψ(1S) in deep inelastic exclusive ep scattering at HERA

    NASA Astrophysics Data System (ADS)

    Ciborowsk, Jacek

    2016-11-01

    The exclusive deep inelastic electroproduction of ψ (2S) and J/ψ (1S) at an ep centre-of-mass energy of 317 GeV has been studied with the ZEUS detector at HERA in the kinematic range 2 < Q2 < 80 GeV2, 30 < W < 210 GeV and |t| < 1 GeV2, where Q2 is the photon virtuality, W is the photon-proton centre-of-mass energy and t is the squared four-momentum transfer at the proton vertex. The data for 2 < Q2 < 5 GeV2 were taken in the HERAI running period and correspond to an integrated luminosity of 114 pb-1. The data for 5 < Q2 < 80 GeV2 are from both HERAI and HERAII periods and correspond to an integrated luminosity of 468 pb-1. The decay modes analysed were μ+ μ- and J/ψ (1S) π+ π- for the ψ (2S) and μ+ μ- for the J/ψ(1S). The cross-section ratio σψ(2S)/σJ/ψ(1S) has been measured as a function of Q2; W and t. The results are compared to predictions of QCD-inspired models of exclusive vector-meson production.

  15. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

    PubMed Central

    Rothman, Nathaniel; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Malats, Nuria; Wu, Xifeng; Figueroa, Jonine; Real, Francisco X; Van Den Berg, David; Matullo, Giuseppe; Baris, Dalsu; Thun, Michael; Kiemeney, Lambertus A; Vineis, Paolo; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P; Rafnar, Thorunn; Hildebrandt, Michelle A T; Kiltie, Anne E; Cussenot, Olivier; Golka, Klaus; Kumar, Rajiv; Taylor, Jack A; Mayordomo, Jose I; Jacobs, Kevin B; Kogevinas, Manolis; Hutchinson, Amy; Wang, Zhaoming; Fu, Yi-Ping; Prokunina-Olsson, Ludmila; Burdette, Laurie; Yeager, Meredith; Wheeler, William; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Jacobs, Eric J; Diver, W Ryan; Gapstur, Susan M; Weinstein, Stephanie J; Virtamo, Jarmo; Cortessis, Victoria K; Gago-Dominguez, Manuela; Pike, Malcolm C; Stern, Mariana C; Yuan, Jian-Min; Hunter, David; McGrath, Monica; Dinney, Colin P; Czerniak, Bogdan; Chen, Meng; Yang, Hushan; Vermeulen, Sita H; Aben, Katja K; Witjes, J Alfred; Makkinje, Remco R; Sulem, Patrick; Besenbacher, Soren; Stefansson, Kari; Riboli, Elio; Brennan, Paul; Panico, Salvatore; Navarro, Carmen; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Trichopoulos, Dimitrios; Caporaso, Neil; Landi, Maria Teresa; Canzian, Federico; Ljungberg, Borje; Tjonneland, Anne; Clavel-Chapelon, Francoise; Bishop, David T; Teo, Mark T W; Knowles, Margaret A; Guarrera, Simonetta; Polidoro, Silvia; Ricceri, Fulvio; Sacerdote, Carlotta; Allione, Alessandra; Cancel-Tassin, Geraldine; Selinski, Silvia; Hengstler, Jan G; Dietrich, Holger; Fletcher, Tony; Rudnai, Peter; Gurzau, Eugen; Koppova, Kvetoslava; Bolick, Sophia C E; Godfrey, Ashley; Xu, Zongli; Sanz-Velez, José I; García-Prats, María D; Sanchez, Manuel; Valdivia, Gabriel; Porru, Stefano; Benhamou, Simone; Hoover, Robert N; Fraumeni, Joseph F; Silverman, Debra T; Chanock, Stephen J

    2010-01-01

    We conducted a multi-stage, genome-wide association study (GWAS) of bladder cancer with a primary scan of 589,299 single nucleotide polymorphisms (SNPs) in 3,532 cases and 5,120 controls of European descent (5 studies) followed by a replication strategy, which included 8,381 cases and 48,275 controls (16 studies). In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1; rs1014971, (P=8×10−12) maps to a non-genic region of chromosome 22q13.1; rs8102137 (P=2×10−11) on 19q12 maps to CCNE1; and rs11892031 (P=1×10−7) maps to the UGT1A cluster on 2q37.1. We confirmed four previous GWAS associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P=4×10−11) and a tag SNP for NAT2 acetylation status (P=4×10−11), as well as demonstrated smoking interactions with both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into mechanisms of carcinogenesis. PMID:20972438

  16. pH Dependence of Photoinduced Electron Transfer with [Ru(TAP)3](2).

    PubMed

    Troian-Gautier, Ludovic; Mugeniwabagara, Epiphanie; Fusaro, Luca; Moucheron, Cécile; Kirsch-De Mesmaeker, Andrée; Luhmer, Michel

    2017-02-20

    The quenching of the excited state of [Ru(TAP)3](2+) (TAP = 1,4,5,8-tetraazaphenanthrene) by guanosine-5'-monophosphate (GMP), N-acetyltyrosine (N-Ac-Tyr), and hydroquinone (H2Q) has been studied in aqueous solution over a wide range of pH values including, for the first time, strongly acidic media. This quenching by electron transfer was examined by steady-state (1)H photochemically induced dynamic nuclear polarization (photo-CIDNP) as well as by more conventional techniques, among which are pulsed laser-induced transient absorption and emission experiments. A deeper knowledge of the photochemical behavior of [Ru(TAP)3](2+) has been gained thanks to the combined use of these two approaches, photo-CIDNP and electronic spectroscopies, highlighting their complementarity. In contrast to what was believed, it is found that the protonated excited state of [Ru(TAP)3](2+) may give rise to an electron transfer with N-Ac-Tyr and H2Q. Such a photoinduced electron transfer does not occur with protonated GMP, however. (1)H photo-CIDNP experiments are expected to be particularly promising for characterization of the reductive quenching of excited-state ruthenium(II) polypyridyl complexes comprising several nonequivalent protonation sites.

  17. Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta

    PubMed Central

    Parry, David A.; Mighell, Alan J.; El-Sayed, Walid; Shore, Roger C.; Jalili, Ismail K.; Dollfus, Hélène; Bloch-Zupan, Agnes; Carlos, Roman; Carr, Ian M.; Downey, Louise M.; Blain, Katharine M.; Mansfield, David C.; Shahrabi, Mehdi; Heidari, Mansour; Aref, Parissa; Abbasi, Mohsen; Michaelides, Michel; Moore, Anthony T.; Kirkham, Jennifer; Inglehearn, Chris F.

    2009-01-01

    The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization. PMID:19200525

  18. SCN2A-Related Early-Onset Epileptic Encephalopathy Responsive to Phenobarbital

    PubMed Central

    Baumer, Fiona M.; Peters, Jurriaan M.; El Achkar, Christelle M.; Pearl, Phillip L.

    2016-01-01

    Voltage-gated sodium channels (Nav) are critical regulators of neuronal excitability. Genes for the α-subunits of three sodium channel subtypes—SCN1A, SCN2A, and SCN3A—are all located on chromosome 2q24. A full-term boy with an unremarkable birth history presented at 1 month of age with unusual movements that had started on day of life 2. Exam was notable for lack of visual attention, hypotonia, and hyperreflexia. Electroencephalogram (EEG) showed an invariant burst suppression with multifocal spikes, ictal episodes with bicycling movements associated with buildups of rhythmic activity, and epileptic spasms. Work-up revealed a 1.77-Mb duplication at locus 2q24.3, encompassing the entirety of SCN2A and SCN3A, but not SCN1A. Phenobarbital led to rapid resolution of the clinical seizures and EEG background normalized other than rare sharp waves. Early-onset epileptic encephalopathy (EOEE), with neonatal seizures, burst suppression, and reversibility with phenobarbital, is part of the enlarging spectrum of Nav channelopathies. The delayed diagnosis provided an unusual opportunity to view the early natural history of this disorder and its remarkable responsiveness to barbiturate therapy. The clinical and EEG response to phenobarbital implicates seizures as the cause of the encephalopathy. PMID:27595042

  19. Measuring reactive hyperemia in the lower limb using near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Willingham, Thomas B.; Southern, William M.; McCully, Kevin K.

    2016-09-01

    Near-infrared spectroscopy (NIRS) has been used to measure reactive hyperemia following a vascular occlusion. However, the procedures and methods of analysis used have varied. The purpose of the present study is to identify reproducible methods for measuring reactive hyperemia using HbO2 NIRS signals in the calf and foot. Healthy participants (10 male, 10 female) aged 19 to 28 years performed one of two tests: reproducibility trials or elevation protocol (30 and 60 cm limb elevation above the heart). The time to 50% reperfusion (T) and the second (R2q) quartile rates of reperfusion were found to be the most reproducible parameters (coefficient of variation=7.12 to 14.1%). The time to 95% reperfusion (T95) was 12.7% more reproducible on average than the previously reported parameter of time to peak hyperemia. Measures of reperfusion time and rate slowed with increasing limb elevation. Correlations were identified between the calf and foot in the measurements of R2q (R2=0.713, p=0.021), T (R2=0.673, p=0.033), and T95 (R2=0.792, p=0.006). Half and 95% recovery times and second and third quartile rates expressed good reproducibility and sensitivity to change with reduced perfusion pressure. NIRS measures of reactive hyperemia have the potential to evaluate microvascular perfusion in clinical populations.

  20. A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.

    PubMed

    Salaverria, Itziar; Martin-Guerrero, Idoia; Wagener, Rabea; Kreuz, Markus; Kohler, Christian W; Richter, Julia; Pienkowska-Grela, Barbara; Adam, Patrick; Burkhardt, Birgit; Claviez, Alexander; Damm-Welk, Christine; Drexler, Hans G; Hummel, Michael; Jaffe, Elaine S; Küppers, Ralf; Lefebvre, Christine; Lisfeld, Jasmin; Löffler, Markus; Macleod, Roderick A F; Nagel, Inga; Oschlies, Ilske; Rosolowski, Maciej; Russell, Robert B; Rymkiewicz, Grzegorz; Schindler, Detlev; Schlesner, Matthias; Scholtysik, René; Schwaenen, Carsten; Spang, Rainer; Szczepanowski, Monika; Trümper, Lorenz; Vater, Inga; Wessendorf, Swen; Klapper, Wolfram; Siebert, Reiner

    2014-02-20

    The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.

  1. Karyotypic relationships in Asiatic asses (kulan and kiang) as defined using horse chromosome arm-specific and region-specific probes.

    PubMed

    Musilova, Petra; Kubickova, Svatava; Horin, Petr; Vodicka, Roman; Rubes, Jiri

    2009-01-01

    Cross-species chromosome painting has been applied to most of the species making up the numerically small family Equidae. However, comparative mapping data were still lacking in Asiatic asses kulan (Equus hemionus kulan) and kiang (E. kiang). The set of horse arm-specific probes generated by laser microdissection was hybridized onto kulan (E. hemionus kulan) and kiang (E. kiang) chromosomes in order to establish a genome-wide chromosomal correspondence between these Asiatic asses and the horse. Moreover, region-specific probes were generated to determine fusion configuration and orientation of conserved syntenic blocks. The kulan karyotype (2n = 54) was ascertained to be almost identical to the previously investigated karyotype of onager E. h. onager (2n = 56). The only difference is in fusion/fission of chromosomes homologous to horse 2q/3q, which are involved in chromosome number polymorphism in many Equidae species. E. kiang karyotype differs from the karyotype of E. hemionus by two additional fusions 8q/15 and 7/25. Chromosomes equivalent to 2q and 3q are not fused in kiang individuals with 2n = 52. Several discrepancies in centromere positions among kulan, kiang and horse chromosomes have been described. Most of the chromosome fusions in Asiatic asses are of centromere-centromere type. Comparative chromosome painting in kiang completed the efforts to establish chromosomal homologies in all representatives of the family Equidae. Application of region-specific probes allows refinement comparative maps of Asiatic asses.

  2. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

    PubMed Central

    Couch, Fergus J.; Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A.; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Blank, Stephanie V.; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J.; Chung, Wendy K.; Claes, Kathleen B. M.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C.; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia M.; dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M.; Eccles, Diana M.; Ehrencrona, Hans; Ekici, Arif B.; Eliassen, Heather; Ellis, Steve; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D.; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D.; Ganz, Patricia A.; Gapstur, Susan M.; Garber, Judy; Gaudet, Mia M.; Gayther, Simon A.; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G.; Glendon, Gord; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hansen, Thomas V. O.; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E.; Herzog, Josef; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Humphreys, Keith; Hunter, David J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y.; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G.; Knight, Julia A.; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L.; Makalic, Enes; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W. M.; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L.; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M.; Muranen, Taru A.; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nordestgaard, Børge G.; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Osorio, Ana; Park, Sue K.; Peeters, Petra H.; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J.; Sanchez, Maria-Jose; Santella, Regina M.; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I.; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary B.; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E.; Tollenaar, Robert A. E. M.; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H. M.; van Rensburg, Elizabeth J.; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N.; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Monteiro, Alvaro A. N.; García-Closas, Montserrat; Easton, Douglas F.

    2016-01-01

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. PMID:27117709

  3. Genetic Aspects of Preeclampsia and the HELLP Syndrome

    PubMed Central

    Mortensen, Jan Helge; Nagy, Bálint

    2014-01-01

    Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases. PMID:24991435

  4. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.

    PubMed

    Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez, Mirsha; Mendoza-Revilla, Javier; Camilo Chacón-Duque, Juan; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Lozano, Rodrigo Barquera; Pérez, Gastón Macín; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Cheeseman, Michael; Rosique, Javier; Bedoya, Gabriel; Rothhammer, Francisco; Headon, Denis; González-José, Rolando; Balding, David; Ruiz-Linares, Andrés

    2016-05-19

    We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

  5. Test of 600 and 750 MeV NN matrix on elastic scattering Glauber model calculations

    NASA Astrophysics Data System (ADS)

    Brissaud, I.

    1980-09-01

    The 600 and 750 MeV proton nucleus elastic scattering cross section and polarization calculations have been performed in the framework of the Glauber model to test the pp and pn scattering amplitudes deduced from a phase shift analysis by Bystricky, Lechanoine and Lehar. It is well known that up to now we do not possess a non-phenomenological NN scattering matrix at intermediate energies. However proton-nucleus scattering analyses are used to extract information about short range correlations1), Δ resonance2) or pion condensation presences)... etc. Most scattering calculations made at these energies have been done with phenomenological NN amplitudes having a gaussian q-dependence 10050_2005_Article_BF01438168_TeX2GIFE1.gif A(q) = {kσ }/{4π }(α + i) e^{ - β ^2 q^2 /2} and 10050_2005_Article_BF01438168_TeX2GIFE2.gif C(q) = {kσ }/{4π }iq(α + i) D_e - β ^2 q^2 /2 K and σ being respectively the projectile momentum and the total pN total cross section. The parameters α, β and D are badly known and are adjusted by fitting some specific reactions as p+4He elastic scattering4). Even when these amplitudes provide good fits to the data, our understanding of the dynamics of the scattering remains obscure.

  6. Genome-wide analyses identify common variants associated with macular telangiectasia type 2.

    PubMed

    Scerri, Thomas S; Quaglieri, Anna; Cai, Carolyn; Zernant, Jana; Matsunami, Nori; Baird, Lisa; Scheppke, Lea; Bonelli, Roberto; Yannuzzi, Lawrence A; Friedlander, Martin; Egan, Catherine A; Fruttiger, Marcus; Leppert, Mark; Allikmets, Rando; Bahlo, Melanie

    2017-02-27

    Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10(-8)) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10(-17); rs715 at 2q34, P = 9.97 × 10(-14); rs477992 at 1p12, P = 2.60 × 10(-12)) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10(-6)) and serine (P = 2.48 × 10(-4)) between MacTel cases and controls.

  7. Updates on the Studies of $${\\varvec{N}}^\\mathbf{*}$$ N * Structure with CLAS and the Prospects with CLAS12

    DOE PAGES

    Mokeev, V. I.

    2016-06-16

    Here, the recent results onmore » $$\\gamma_vpN^*$$ electrocouplings from analyses of the data on exclusive meson electroproduction off protons measured with the CLAS detector at Jefferson Lab are presented. The impact of these results on the exploration of the excited nucleon state structure and non-perturbative strong interaction dynamics behind its formation is outlined. The future extension of these studies in the experiments with the CLAS12 detector in the upgraded Hall-B at JLab will provide for the first time $$\\gamma_vpN^*$$ electrocouplings of all prominent resonances at the still unexplored distance scales that correspond to extremely low (0.05~GeV$^2 < Q^2 <$ 0.5~GeV$^2$) and the highest photon virtualities (5.0~GeV$^2 < Q^2 <$ 12.0~GeV$^2$) ever achieved in the exclusive electroproduction measurements. The expected results will address the most important open problems of the Standard Model: on the nature of more than 98\\% of hadron mass, quark-gluon confinement and emergence of the excited nucleon state structure from the QCD Lagrangian, as well as allowing a search for the new states of hadron matter predicted from the first principles of QCD, the so-called hybrid baryons.« less

  8. Updates on the Studies of $${\\varvec{N}}^\\mathbf{*}$$ N * Structure with CLAS and the Prospects with CLAS12

    SciTech Connect

    Mokeev, V. I.

    2016-06-16

    Here, the recent results on $\\gamma_vpN^*$ electrocouplings from analyses of the data on exclusive meson electroproduction off protons measured with the CLAS detector at Jefferson Lab are presented. The impact of these results on the exploration of the excited nucleon state structure and non-perturbative strong interaction dynamics behind its formation is outlined. The future extension of these studies in the experiments with the CLAS12 detector in the upgraded Hall-B at JLab will provide for the first time $\\gamma_vpN^*$ electrocouplings of all prominent resonances at the still unexplored distance scales that correspond to extremely low (0.05~GeV$^2 < Q^2 <$ 0.5~GeV$^2$) and the highest photon virtualities (5.0~GeV$^2 < Q^2 <$ 12.0~GeV$^2$) ever achieved in the exclusive electroproduction measurements. The expected results will address the most important open problems of the Standard Model: on the nature of more than 98\\% of hadron mass, quark-gluon confinement and emergence of the excited nucleon state structure from the QCD Lagrangian, as well as allowing a search for the new states of hadron matter predicted from the first principles of QCD, the so-called hybrid baryons.

  9. Phenotype of a child with Angelman syndrome born to a woman with Prader-Willi syndrome.

    PubMed

    Ostergaard, John R

    2015-09-01

    This report describes the phenotype, from early childhood to adolescence, of a girl with Angelman syndrome (AS) born following a maternal transmission of a germline paternal 15q11.2-q13 deletion. During early childhood, she showed a typical AS phenotype, such as jerky movements, poor sleep, high voltage electroencephalography pattern, epilepsy, and a severe developmental disability. As she grew older, indications of phenotypical traits similar to Prader-Willi syndrome (PWS) appeared, in particular hyperphagic behavior and a body fat distribution similar to that reported in PWS. She generally showed cheerful AS behavior and had the characteristic outbursts of laughter, but her attitude to other people did not reflect the usual shared enjoyment of interaction seen in children with AS. In unfamiliar surroundings, she withdrew socially, similar to children with PWS, and her insistence on the same, rigid routines was similar to behavior patterns in PWS. The dysmorphic facial features that characterize AS were blurred in adolescence. The specified features that this AS patient had in common with PWS were hardly incidental and, if verified by upcoming case reports of children born to women with a paternal 15q11.2-q13 deletion, they may show new aspects of genetic imprinting.

  10. Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.

    PubMed

    Heilmann, Stefanie; Kiefer, Amy K; Fricker, Nadine; Drichel, Dmitriy; Hillmer, Axel M; Herold, Christine; Tung, Joyce Y; Eriksson, Nicholas; Redler, Silke; Betz, Regina C; Li, Rui; Kárason, Ari; Nyholt, Dale R; Song, Kijoung; Vermeulen, Sita H; Kanoni, Stavroula; Dedoussis, George; Martin, Nicholas G; Kiemeney, Lambertus A; Mooser, Vincent; Stefansson, Kari; Richards, J Brent; Becker, Tim; Brockschmidt, Felix F; Hinds, David A; Nöthen, Markus M

    2013-06-01

    The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10(-8)2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10(-15)) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

  11. Comparative analysis of a BAC contig of the porcine RN region and the human transcript map: implications for the cloning of trait loci.

    PubMed

    Jeon, J T; Amarger, V; Rogel-Gaillard, C; Robic, A; Bongcam-Rudloff, E; Paul, S; Looft, C; Milan, D; Chardon, P; Andersson, L

    2001-03-15

    The poorly developed transcript maps and the limited resources for genome analysis hamper positional cloning of trait loci in farm animals. This study demonstrates that this will now be easier by the combined use of BAC contigs and the import of the near complete human transcript map. The conclusion was obtained by a comparative analysis of a 2.4-Mb BAC contig of the RN region in pigs. The contig was constructed as part of a successful positional cloning project, which identified PRKAG3 as the causative gene for the RN phenotype. A comparative map including the corresponding regions on human chromosome 2q35 and mouse chromosome 1 (region 36-44 cM) is reported. Sixteen coding sequences were mapped on the BAC contig. The majority of these were identified by BLAST searches of BAC end sequences and BAC shotgun sequences generated during the positional cloning project. Map data for the orthologues in humans were available for 12 of the 16 coding sequences, and all 12 have been assigned to 2q35. Furthermore, no evidence for any rearrangement in gene order was obtained. The extensive linkage conservation indicates that the near complete human transcript map will be an invaluable resource for positional cloning projects in pigs and other domestic animals.

  12. A novel locus for split-hand/foot malformation associated with tibial hemimelia (SHFLD syndrome) maps to chromosome region 17p13.1-17p13.3.

    PubMed

    Lezirovitz, Karina; Maestrelli, Sylvia Regina Pedrosa; Cotrim, Nelson Henderson; Otto, Paulo A; Pearson, Peter L; Mingroni-Netto, Regina Celia

    2008-07-01

    Split-hand/foot malformation (SHFM) associated with aplasia of long bones, SHFLD syndrome or Tibial hemimelia-ectrodactyly syndrome is a rare condition with autosomal dominant inheritance, reduced penetrance and an incidence estimated to be about 1 in 1,000,000 liveborns. To date, three chromosomal regions have been reported as strong candidates for harboring SHFLD syndrome genes: 1q42.2-q43, 6q14.1 and 2q14.2. We characterized the phenotype of nine affected individuals from a large family with the aim of mapping the causative gene. Among the nine affected patients, four had only SHFM of the hands and no tibial defects, three had both defects and two had only unilateral tibial hemimelia. In keeping with previous publications of this and other families, there was clear evidence of both variable expression and incomplete penetrance, the latter bearing hallmarks of anticipation. Segregation analysis and multipoint Lod scores calculations (maximum Lod score of 5.03 using the LINKMAP software) using all potentially informative family members, both affected and unaffected, identified the chromosomal region 17p13.1-17p13.3 as the best and only candidate for harboring a novel mutated gene responsible for the syndrome in this family. The candidate gene CRK located within this region was sequenced but no pathogenic mutation was detected.

  13. Evaluation of a lattice Boltzmann method in a complex nanoflow.

    PubMed

    Suga, K; Takenaka, S; Ito, T; Kaneda, M; Kinjo, T; Hyodo, S

    2010-07-01

    In order to establish a cost-effective strategy to simulate complex flows in continuum to slip and transitional regimes, the present study assesses the performance of a lattice Boltzmann method (LBM) formerly discussed by the present authors' group [Niu, Phys. Rev. E 76, 036711 (2007)]. This LBM is based on a diffuse scattering wall boundary condition, a regularization procedure, and an effective relaxation time associated with the Knudsen number. The present assessment is on its regularization procedure and third-order truncated system based on the two-dimensional twenty-one discrete velocity (D2Q21) model for the Cartesian lattices. The test flow cases are force-driven Poiseuille flows, the Couette flows and a flow around a square cylinder situated in a nanochannel. For producing the reference data of the square cylinder flow, the molecular dynamics simulation using Lennard-Jones potential is also performed. Although the flow profiles and the slip velocities of the Poiseuille flows and the Couette flows are more accurately predicted by the third-order truncated system, the general velocity profiles around the square cylinder are also well predicted by the second-order truncated system based on the two-dimensional nine discrete velocity (D2Q9) model. It is also confirmed that without the regularization process, the entire flow field prediction suffers unphysical momentum oscillations around the square cylinder.

  14. Nonlinear neural networks. II. Information processing

    NASA Astrophysics Data System (ADS)

    van Hemmen, J. L.; Grensing, D.; Huber, A.; Kühn, R.

    1988-01-01

    Information processing in nonlinear neural networks with a finite number q of stored patterns is studied. Each network is characterized completely by its synaptic kernel Q. At low temperatures, the nonlinearity typically results in 2q-2- q metastable, pure states in addition to the q retrieval states that are associated with the q stored patterns. These spurious states start appearing at a temperaturetilde T_q , which depends on q. We give sufficient conditions to guarantee that the retrieval states bifurcate first at a critical temperature T c and thattilde T_q / T c → 0 as q→∞. Hence, there is a large temperature range where only the retrieval states and certain symmetric mixtures thereof exist. The latter are unstable, as they appear at T c . For clipped synapses, the bifurcation and stability structure is analyzed in detail and shown to approach that of the (linear) Hopfield model as q→∞. We also investigate memories that forget and indicate how forgetfulness can be explained in terms of the eigenvalue spectrum of the synaptic kernel Q.

  15. Magnetic and charge structures in itinerant-electron magnets: Coexistence of multiple spin-density and charge-density waves

    NASA Astrophysics Data System (ADS)

    Ohkawa, Fusayoshi J.

    2002-06-01

    A theory of Kondo lattices is applied to studying possible magnetic and charge structures of itinerant-electron antiferromagnets. Even helical spin structures can be stabilized when the nesting of the Fermi surface is not sharp and the superexchange interaction, which arises from the virtual exchange of pair excitations across the Mott-Hubbard gap, is mainly responsible for magnetic instability. Sinusoidal spin structures or spin-density waves (SDW's) are only stabilized when the nesting of the Fermi surface is sharp enough or when an exchange interaction arising from that of pair excitations of quasiparticles is mainly responsible for magnetic instability. In particular, multiple SDW's are stabilized when their incommensurate ordering wave numbers +/-Q are multiple; magnetizations of different +/-Q components are orthogonal to each other in double and triple SDW's when magnetic anisotropy is weak enough. Unless +/-2Q are commensurate, charge-density waves (CDW's) with +/-2Q coexist with SDW's with +/-Q. Because the quenching of magnetic moments by the Kondo effect or local quantum spin fluctuations depends on local numbers of electrons, the phase of CDW's or electron densities is such that magnetic moments are large where the quenching is weak. It is proposed that the so-called stripe order must be the coexisting state of double incommensurate SDW's and CDW's in tetragonal cuprate-oxide high temperature superconductors, in particular, those with the square CuO2 lattices.

  16. Allelic variants of IL1R1 gene associate with severe hand osteoarthritis

    PubMed Central

    2010-01-01

    Background In search for genes predisposing to osteoarthritis (OA), several genome wide scans have provided evidence for linkage on 2q. In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families. Methods We genotyped 32 single nucleotide polymorphisms (SNPs) in this 470 kb region comprising six genes belonging to the interleukin 1 superfamily and monitored for association with individual SNPs and SNP haplotypes among severe familial hand OA cases (material extended from our previous linkage study; n = 134), unrelated end-stage bilateral primary knee OA cases (n = 113), and population based controls (n = 436). Results Four SNPs in the IL1R1 gene, mapping to a 125 kb LD block, provided evidence for association with hand OA in family-based and case-control analysis, the strongest association being with SNP rs2287047 (p-value = 0.0009). Conclusions This study demonstrates an association between severe hand OA and IL1R1 gene. This gene represents a highly relevant biological candidate since it encodes protein that is a known modulator of inflammatory processes associated with joint destruction and resides within a locus providing consistent evidence for linkage to hand OA. As the observed association did not fully explain the linkage obtained in the previous study, it is plausible that also other variants in this genome region predispose to hand OA. PMID:20353565

  17. Detection of a complex translocation using fluorescent in situ hybridization (FISH)

    SciTech Connect

    Rosen, B.A.; Abuelo, D.N.; Mark, H.F.

    1994-09-01

    The use of fluorescent in situ hybridization (FISH) allowed the detection of a complex 3-way translocation in a patient with multiple congenital malformations and mental retardation. The patient was a 10-year-old girl with mental retardation, seizures, repaired cleft palate, esotropia, epicanthal folds, broad nasal bridge, upward slanting palpebral fissures, single transverse palmar crease, brachydactyly, hypoplastic nails, ectrodactyly between the third and fourth right toes, and hypoplasia of the left third toe. Chromosome analysis performed at birth was reported as normal. We performed high resolution banding analysis which revealed an apparently balanced translocation between chromosomes 2 and 9. However, because of her multiple abnormalities, further studies were ordered. Fluorescent in situ hybridization (FISH) using chromosome painting probes revealed a karyotype of 46,XX,t(2;8;9) (2pter{yields}q31::8q21.2{yields}8qter; 8pter{yields}q21.2::2q31{yields}q34::9q34{yields}qter; 9pter{yields}q34::2q34{yields}qter). The 3-way translocation appears to be de novo, as neither parent is a translocation carrier. This case illustrates the importance of using FISH to further investigate cases of apparently balanced translocations in the presence of phenotypic abnormalities and/or mental retardation.

  18. Potassium and magnesium succinatouranilates - Synthesis and crystal structure

    NASA Astrophysics Data System (ADS)

    Novikov, S. A.; Grigoriev, M. S.; Serezhkina, L. B.; Serezhkin, V. N.

    2017-04-01

    Single crystal X-ray diffraction has been applied to determine the structures of two new uranyl coordination polymers: K2[(UO2)2(C4H4O4)3] (1) and [Mg(H2O)6] [(UO2)2(C4H4O4)3]·2H2O (2), where C4H4O42- is succinate anion. Crystals of 1 and 2 contain polymeric complex anions [(UO2)2(C4H4O4)3]2- with the same A2Q023 crystallochemical formula (A=UO22+, Q02=C4O4H42-), and have layered (1) or chain (2) structure. It has been found, that conformation of succinate ions is one of the factors, which affects the structure of [(UO2)2(C4H4O4)3]2- anions. IR spectra of these new compounds are in good agreement with crystallographic data. Topological analysis of the uranium dicarboxylates with A2Q023 crystallochemical formula has shown the presence of five isomers which differ from each other in coordination sequences and / or dimensionality.

  19. Treatment of a slaughterhouse wastewater: effect of internal recycle rate on chemical oxygen demand, total Kjeldahl nitrogen and total phosphorus removal.

    PubMed

    Fongsatitkul, P; Wareham, D G; Elefsiniotis, P; Charoensuk, P

    2011-12-01

    This study investigated the ability of an anaerobic/anoxic/oxic (A2/O) system to treat a slaughterhouse wastewater. The system employed two identical continuous-flow reactors (101 total liquid volume each) running in parallel with the main operational variable, being the internal recycle (IR) rate. The chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN) and total phosphorus (TP) performance was evaluated as the IR flowrate was increased from a Q of 151d(-1) to 4Q at a system hydraulic retention time of 16 h and a solids retention time of 10 d. The COD:TKN and COD:TP ratios were 8.2:1 and 54:1, which supported both nitrogen and phosphorus removal. For all IR multiples of Q, the COD removal was in excess of 90%. The TKN removal showed a modest improvement (a 4-5% increase, depending on the dissolved oxygen (DO)) as the IR doubled from Q to 2Q, but no further increase was observed at the 4Q IR rate. The TP removal reached its optimum (around 85%-89% (again depending on the DO)) at the 2Q rate.

  20. A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3 Mb deletion encompassing GLI2.

    PubMed

    Kevelam, Sietske H G; van Harssel, Jeske J T; van der Zwaag, Bert; Smeets, Hubertus J M; Paulussen, Aimee D C; Lichtenbelt, Klaske D

    2012-01-01

    Loss-of-function mutations of GLI2 are associated with features at the mild end of the holoprosencephaly spectrum, including abnormal pituitary gland formation and/or function, and craniofacial abnormalities. In addition patients may have branchial arch anomalies and polydactyly. Large, microscopically visible, interstitial deletions spanning 2q14.2 have been reported in patients with multiple congenital anomalies and intellectual disability. We report here on a patient with a mild holoprosencephaly spectrum phenotype (bilateral cleft lip and palate and abnormal pituitary gland formation with panhypopituitarism) and normal psychomotor development, who was found to carry a 1.3 Mb submicroscopic heterozygous deletion in 2q14.2, encompassing the GLI2 gene. We review the genotype and phenotype of previously published probands with GLI2 aberrations. Our findings confirm the association of haploinsufficiency of GLI2 and mild HPE spectrum features. Consistent with prior reports, we observed incomplete penetrance of the deletion in the family, illustrating the multifactorial etiology of holoprosencephaly spectrum features. In addition to the holoprosencephaly spectrum features, the proband had heterotaxy of the abdominal organs. Mutations in the known heterotaxy genes (NODAL, ZIC3 and CFC1) were excluded. The deletion contains five genes, in addition to GLI2, including the EPB4.1l5 gene. Based on findings in Epb4.1l5 mutant mice we hypothesize that Epb4.1l5 is a candidate gene for the heterotaxy observed in the proband.

  1. IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry

    PubMed Central

    Sanabria-Salas, María Carolina; Hernández-Suárez, Gustavo; Umaña-Pérez, Adriana; Rawlik, Konrad; Tenesa, Albert; Serrano-López, Martha Lucía; Sánchez de Gómez, Myriam; Rojas, Martha Patricia; Bravo, Luis Eduardo; Albis, Rosario; Plata, José Luis; Green, Heather; Borgovan, Theodor; Li, Li; Majumdar, Sumana; Garai, Jone; Lee, Edward; Ashktorab, Hassan; Brim, Hassan; Li, Li; Margolin, David; Fejerman, Laura; Zabaleta, Jovanny

    2017-01-01

    Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31–3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk. PMID:28157220

  2. Linkage approach and direct COL4A5 gene mutation screening in Alport syndrome

    SciTech Connect

    Turco, A.E.; Rossetti, S.; Biasi, O.

    1994-09-01

    Alport Syndrome (AS) is transmitted as an X-linked dominant trait in the majority of families, the defective gene being COL4A5 at Xq22. In the remaining cases AS appears to be autosomally inherited. Recently, mutations in COL4A3 and COL4A4 genes at 2q35-q37 were identified in families with autosomal recessive AS. Mutation detection screening is being performed by non-radioactive single stand conformation polymorphism (SSCP), heteroduplex analysis, and automated DNA sequencing in over 170 AS patients enrolled in the ongoing Italian Multicenter Study on AS. So far twenty-five different mutations have been found, including missense, splicing, and frameshifts. Moreover, by using six tightly linked COL4A5 informative makers, we have also typed two larger AS families, and have shown compatible sex-linked transmission in one other, suggesting autosomal recessive inheritance. In this latter three-generation COL4A5-unlinked family we are now looking for linkage and for mutations in the candidate COL4A3 and COL4A4 genes on chromosome 2q.

  3. Strong tidal dissipation in Io and Jupiter from astrometric observations.

    PubMed

    Lainey, Valéry; Arlot, Jean-Eudes; Karatekin, Ozgür; Van Hoolst, Tim

    2009-06-18

    Io is the volcanically most active body in the Solar System and has a large surface heat flux. The geological activity is thought to be the result of tides raised by Jupiter, but it is not known whether the current tidal heat production is sufficiently high to generate the observed surface heat flow. Io's tidal heat comes from the orbital energy of the Io-Jupiter system (resulting in orbital acceleration), whereas dissipation of energy in Jupiter causes Io's orbital motion to decelerate. Here we report a determination of the tidal dissipation in Io and Jupiter through its effect on the orbital motions of the Galilean moons. Our results show that the rate of internal energy dissipation in Io (k(2)/Q = 0.015 +/- 0.003, where k(2) is the Love number and Q is the quality factor) is in good agreement with the observed surface heat flow, and suggest that Io is close to thermal equilibrium. Dissipation in Jupiter (k(2)/Q = (1.102 +/- 0.203) x 10(-5)) is close to the upper bound of its average value expected from the long-term evolution of the system, and dissipation in extrasolar planets may be higher than presently assumed. The measured secular accelerations indicate that Io is evolving inwards, towards Jupiter, and that the three innermost Galilean moons (Io, Europa and Ganymede) are evolving out of the exact Laplace resonance.

  4. Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families.

    PubMed

    Wedenoja, J; Loukola, A; Tuulio-Henriksson, A; Paunio, T; Ekelund, J; Silander, K; Varilo, T; Heikkilä, K; Suvisaari, J; Partonen, T; Lönnqvist, J; Peltonen, L

    2008-07-01

    Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.

  5. Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease

    PubMed Central

    Hartiala, Jaana A.; Wilson Tang, W. H.; Wang, Zeneng; Crow, Amanda L.; Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth; Erdmann, Jeanette; Willenborg, Christina; Hazen, Stanley L.; Allayee, Hooman

    2016-01-01

    Metabolites derived from dietary choline and L-carnitine, such as trimethylamine N-oxide and betaine, have recently been identified as novel risk factors for atherosclerosis in mice and humans. We sought to identify genetic factors associated with plasma betaine levels and determine their effect on risk of coronary artery disease (CAD). A two-stage genome-wide association study (GWAS) identified two significantly associated loci on chromosomes 2q34 and 5q14.1. The lead variant on 2q24 (rs715) localizes to carbamoyl-phosphate synthase 1 (CPS1), which encodes a mitochondrial enzyme that catalyses the first committed reaction and rate-limiting step in the urea cycle. Rs715 is also significantly associated with decreased levels of urea cycle metabolites and increased plasma glycine levels. Notably, rs715 yield a strikingly significant and protective association with decreased risk of CAD in only women. These results suggest that glycine metabolism and/or the urea cycle represent potentially novel sex-specific mechanisms for the development of atherosclerosis. PMID:26822151

  6. Genetics of isolated and syndromic strabismus: facts and perspectives.

    PubMed

    Lorenz, Birgit

    2002-06-01

    Family studies have demonstrated the genetic etiology of concomitant strabismus (prevalence in different populations 1-5%, positive family history in 37% on average), as have twin studies (mean concordance in monozygous twins 73% compared to 35% in dizygous twins). In Duane's syndrome, three chromosomal loci have been identified to date: 2q31, 8q13, and 22q11; loci have also been identified in Moebius syndrome (various inheritance patterns): 13q12.2-q13, 3q21-q22, and 10q21.3-q22, as well as in congenital fibrosis of the extraocular muscles (CFEOM; 3 loci, 1 gene).(1) Already identified are the genes for a number of rarer muscular dystrophy syndromes with ocular involvement, various forms of congenital myasthenia, and mitochondrial diseases (with the primary defect located either in the mtDNA, resulting in a mitochondrial inheritance pattern, or in the nuclear DNA with Mendelian inheritance). A number of hereditary retinal diseases (Mendelian inheritance) may also be associated with strabismus. More than one gene is likely to be involved in the frequently occurring concomitant strabismus, making the analysis more difficult. Patients with chromosomal rearrangements, large families and isolated populations (see also the contributions by Preising and Zitzlsperger et al. in this issue)(2,3) will be instrumental in gene identification. In view of the high prevalence of concomitant strabismus, the disclosure of its etiology will have considerable medical, psychosocial and health-cost impact.

  7. Differential protein structural disturbances and suppression of assembly partners produced by nonsense GABRG2 epilepsy mutations: implications for disease phenotypic heterogeneity

    PubMed Central

    Wang, Juexin; Shen, Dingding; Xia, Geqing; Shen, Wangzhen; Macdonald, Robert L.; Xu, Dong; Kang, Jing-Qiong

    2016-01-01

    Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities. Structural modeling and structure-based analysis indicated that the surface of the wild-type γ2 subunit was naturally hydrophobic, which is suitable to be buried in the cell membrane. Different mutant γ2 subunits had different stabilities and different interactions with their wild-type subunit binding partners because they adopted different conformations and had different surface hydrophobicities and different tendency to dimerize. We utilized flow cytometry and biochemical approaches in combination with lifted whole cell patch-clamp recordings. We demonstrated that the truncated subunits had no to minimal surface expression and unchanged or reduced surface expression of wild-type partnering subunits. The amplitudes of GABA-evoked currents from the mutant α1β2γ2(R136*), α1β2γ2(Q390*) and α1β2γ2(W429*) receptors were reduced compared to the currents from α1β2γ2 receptors but with differentially reduced levels. This thus suggests differential protein structure disturbances are correlated with disease severity. PMID:27762395

  8. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.

    PubMed

    Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

    2016-04-27

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

  9. Q2 evolution of the neutron spin structure moments using a 3He target.

    PubMed

    Amarian, M; Auerbach, L; Averett, T; Berthot, J; Bertin, P; Bertozzi, B; Black, T; Brash, E; Brown, D; Burtin, E; Calarco, J; Cates, G; Chai, Z; Chen, J-P; Choi, Seonho; Chudakov, E; Cisbani, E; De Jager, C W; Deur, A; DiSalvo, R; Dieterich, S; Djawotho, P; Finn, M; Fissum, K; Fonvieille, H; Frullani, S; Gao, H; Gao, J; Garibaldi, F; Gasparian, A; Gilad, S; Gilman, R; Glamazdin, A; Glashausser, C; Goldberg, E; Gomez, J; Gorbenko, V; Hansen, J-O; Hersman, B; Holmes, R; Huber, G M; Hughes, E; Humensky, B; Incerti, S; Iodice, M; Jensen, S; Jiang, X; Jones, C; Jones, G; Jones, M; Jutier, C; Ketikyan, A; Kominis, I; Korsch, W; Kramer, K; Kumar, K; Kumbartzki, G; Kuss, M; Lakuriqi, E; Laveissiere, G; Lerose, J; Liang, M; Liyanage, N; Lolos, G; Malov, S; Marroncle, J; McCormick, K; McKeown, R; Meziani, Z-E; Michaels, R; Mitchell, J; Papandreou, Z; Pavlin, T; Petratos, G G; Pripstein, D; Prout, D; Ransome, R; Roblin, Y; Rowntree, D; Rvachev, M; Sabatie, F; Saha, A; Slifer, K; Souder, P; Saito, T; Strauch, S; Suleiman, R; Takahashi, K; Teijiro, S; Todor, L; Tsubota, H; Ueno, H; Urciuoli, G; Van Der Meer, R; Vernin, P; Voskanian, H; Wojtsekhowski, B; Xiong, F; Xu, W; Yang, J-C; Zhang, B; Zolnierczuk, P

    2004-01-16

    We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

  10. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

    PubMed Central

    Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez, Mirsha; Mendoza-Revilla, Javier; Camilo Chacón-Duque, Juan; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Lozano, Rodrigo Barquera; Pérez, Gastón Macín; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria- Cátira; Canizales-Quinteros, Samuel; Cheeseman, Michael; Rosique, Javier; Bedoya, Gabriel; Rothhammer, Francisco; Headon, Denis; González-José, Rolando; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. PMID:27193062

  11. Measurements of the Electron-Helicity Dependent Cross Sections of Deeply Virtual Compton Scattering with CEBAF at 12 GeV

    SciTech Connect

    J. Roche; C. E. Hyde-Wright; B. Michel; C. Munoz Camacho; et al.

    2006-09-11

    We propose precision measurements of the helicity-dependent and helicity independent cross sections for the ep {yields} ep{gamma} reaction in Deeply Virtual Compton Scattering (DVCS) kinematics. DVCS scaling is obtained in the limits Q{sup 2} >> {Lambda}{sub QCD}{sup 2}, x{sub Bj} fixed, and -{Delta}{sup 2} = -(q-q{prime}){sup 2} << Q{sup 2}. We consider the specific kinematic range Q{sup 2} > 2 GeV{sup 2}, W > 2 GeV, and -{Delta}{sup 2} {le} 1 GeV{sup 2}. We will use our successful technique from the 5.75 GeV Hall A DVCS experiment (E00-110). With polarized 6.6, 8.8, and 11 GeV beams incident on the liquid hydrogen target, we will detect the scattered electron in the Hall A HRS-L spectrometer (maximum central momentum 4.3 GeV/c) and the emitted photon in a slightly expanded PbF{sub 2} calorimeter. In general, we will not detect the recoil proton. The H(e,e{prime}{gamma})X missing mass resolution is sufficient to isolate the exclusive channel with 3% systematic precision.

  12. Measurement of the cross-section ratio σψ(2S)/σJ/ψ(1S) in deep inelastic exclusive ep scattering at HERA

    NASA Astrophysics Data System (ADS)

    Abramowicz, H.; Abt, I.; Adamczyk, L.; Adamus, M.; Antonelli, S.; Aushev, V.; Aushev, Y.; Behnke, O.; Behrens, U.; Bertolin, A.; Bloch, I.; Boos, E. G.; Borras, K.; Brock, I.; Brook, N. H.; Brugnera, R.; Bruni, A.; Bussey, P. J.; Caldwell, A.; Capua, M.; Catterall, C. D.; Chwastowski, J.; Ciborowski, J.; Ciesielski, R.; Cooper-Sarkar, A. M.; Corradi, M.; Corriveau, F.; Dementiev, R. K.; Devenish, R. C. E.; Dolinska, G.; Dusini, S.; Figiel, J.; Foster, B.; Gach, G.; Gallo, E.; Garfagnini, A.; Geiser, A.; Gizhko, A.; Gladilin, L. K.; Golubkov, Yu. A.; Grebenyuk, J.; Gregor, I.; Grzelak, G.; Gueta, O.; Guzik, M.; Hain, W.; Hochman, D.; Hori, R.; Ibrahim, Z. A.; Iga, Y.; Ishitsuka, M.; Iudin, A.; Januschek, F.; Jomhari, N. Z.; Kadenko, I.; Kananov, S.; Karshon, U.; Kaur, M.; Kaur, P.; Kisielewska, D.; Klanner, R.; Klein, U.; Kondrashova, N.; Kononenko, O.; Korol, Ie.; Korzhavina, I. A.; Kotański, A.; Kötz, U.; Kovalchuk, N.; Kowalski, H.; Krupa, B.; Kuprash, O.; Kuze, M.; Levchenko, B. B.; Levy, A.; Libov, V.; Limentani, S.; Lisovyi, M.; Lobodzinska, E.; Löhr, B.; Lohrmann, E.; Longhin, A.; Lontkovskyi, D.; Lukina, O. Yu.; Makarenko, I.; Malka, J.; Mergelmeyer, S.; Mohamad Idris, F.; Mohammad Nasir, N.; Myronenko, V.; Nagano, K.; Nobe, T.; Notz, D.; Nowak, R. J.; Onishchuk, Yu.; Paul, E.; Perlański, W.; Pokrovskiy, N. S.; Przybycień, M.; Roloff, P.; Rubinsky, I.; Ruspa, M.; Saxon, D. H.; Schioppa, M.; Schmidke, W. B.; Schneekloth, U.; Schörner-Sadenius, T.; Shcheglova, L. M.; Shevchenko, R.; Shkola, O.; Shyrma, Yu.; Singh, I.; Skillicorn, I. O.; Słomiński, W.; Solano, A.; Stanco, L.; Stefaniuk, N.; Stern, A.; Stopa, P.; Sztuk-Dambietz, J.; Szuba, D.; Szuba, J.; Tassi, E.; Tokushuku, K.; Tomaszewska, J.; Trofymov, A.; Tsurugai, T.; Turcato, M.; Turkot, O.; Tymieniecka, T.; Verbytskyi, A.; Viazlo, O.; Walczak, R.; Wan Abdullah, W. A. T.; Wichmann, K.; Wing, M.; Wolf, G.; Yamada, S.; Yamazaki, Y.; Zakharchuk, N.; Żarnecki, A. F.; Zawiejski, L.; Zenaiev, O.; Zhautykov, B. O.; Zhmak, N.; Zotkin, D. S.

    2016-08-01

    The exclusive deep inelastic electroproduction of ψ (2 S) and J / ψ (1 S) at an ep centre-of-mass energy of 317 GeV has been studied with the ZEUS detector at HERA in the kinematic range 2 <Q2 < 80 GeV2, 30 < W < 210 GeV and | t | < 1 GeV2, where Q2 is the photon virtuality, W is the photon-proton centre-of-mass energy and t is the squared four-momentum transfer at the proton vertex. The data for 2 <Q2 < 5 GeV2 were taken in the HERA I running period and correspond to an integrated luminosity of 114 pb-1. The data for 5

  13. Symptom dimensions as alternative phenotypes to address genetic heterogeneity in schizophrenia and bipolar disorder.

    PubMed

    Labbe, Aurélie; Bureau, Alexandre; Moreau, Isabel; Roy, Marc-André; Chagnon, Yvon; Maziade, Michel; Merette, Chantal

    2012-11-01

    This study introduces a novel way to use the lifetime ratings of symptoms of psychosis, mania and depression in genetic linkage analysis of schizophrenia (SZ) and bipolar disorder (BP). It suggests using a latent class model developed for family data to define more homogeneous symptom subtypes that are influenced by a smaller number of genes that will thus be more easily detectable. In a two-step approach, we proposed: (i) to form homogeneous clusters of subjects based on the symptom dimensions and (ii) to use the information from these homogeneous clusters in linkage analysis. This framework was applied to a unique SZ and BP sample composed of 1278 subjects from 48 large kindreds from the Eastern Quebec population. The results suggest that our strategy has the power to increase linkage signals previously obtained using the diagnosis as phenotype and allows for a better characterization of the linkage signals. This is the case for a linkage signal, which we formerly obtained in chromosome 13q and enhanced using the dimension mania. The analysis also suggests that the methods may detect new linkage signals not previously uncovered by using diagnosis alone, as in chromosomes 2q (delusion), 15q (bizarre behavior), 7p (anhedonia) and 9q (delusion). In the case of the 15q and 2q region, the results coincide with linkage signals detected in other studies. Our results support the view that dissecting phenotypic heterogeneity by modeling symptom dimensions may provide new insights into the genetics of SZ and BP.

  14. Dipion decays of heavy quarkonium in the field correlator method

    SciTech Connect

    Simonov, Yu. A.

    2008-06-15

    The mechanism of dipion transitions nS {sup {yields}}n'S {pi}{pi} (n = 3, 2; n' = 2, 1) in bottomonium and charmonium is studied with the use of the chiral string-breaking Lagrangian allowing for the emission of any number of {pi}(K, {nu}), and not containing fitting parameters. The transition amplitude contains two terms: M = a - b, where the first term (a) refers to subsequent one-pion emission, {Gamma} (nS) {yields} {pi} B bar B {yields} {pi} {Gamma} (n'S){pi} , and the second term (b) refers to two-pion emission, {Gamma} (nS) {yields} {pi} {pi} B bar B {yields} {pi} {pi} {Gamma} (n'S). The one parameter formula for the dipion mass distribution is derived, dw/dq {approx} (phase space) x vertical bar {eta} - x vertical bar {sup 2}, where x = (q{sup 2} - 4m{sub {pi}}{sup 2})/(q{sub max}{sup 2} - 4m{sub {pi}}{sup 2}), q{sup 2} m= M{sub {pi}{pi}}{sup 2}. The parameter {nu} dependent on the process is calculated, using SHO wave functions and imposing PCAC restrictions (Adler zero) on amplitudes a and b. The resulting dipion mass distributions are in agreement with experimental data.

  15. Large-scale cloning of human chromosome 2-specific yeast artificial chromosomes (YACs) using an interspersed repetitive sequences (IRS)-PCR approach.

    PubMed

    Liu, J; Stanton, V P; Fujiwara, T M; Wang, J X; Rezonzew, R; Crumley, M J; Morgan, K; Gros, P; Housman, D; Schurr, E

    1995-03-20

    We report here an efficient approach to the establishment of extended YAC contigs on human chromosome 2 by using an interspersed repetitive sequences (IRS)-PCR-based screening strategy for YAC DNA pools. Genomic DNA was extracted from 1152 YAC pools comprised of 55,296 YACs mostly derived from the CEPH Mark I library. Alu-element-mediated PCR was performed for each pool, and amplification products were spotted on hybridization membranes (IRS filters). IRS probes for the screening of the IRS filters were obtained by Alu-element-mediated PCR. Of 708 distinct probes obtained from chromosome 2-specific somatic cell hybrids, 85% were successfully used for library screening. Similarly, 80% of 80 YAC walking probes were successfully used for library screening. Each probe detected an average of 6.6 YACs, which is in good agreement with the 7- to 7.5-fold genome coverage provided by the library. In a preliminary analysis, we have identified 188 YAC groups that are the basis for building contigs for chromosome 2. The coverage of the telomeric half of chromosome 2q was considered to be good since 31 of 34 microsatellites and 22 of 23 expressed sequence tags that were chosen from chromosome region 2q13-q37 were contained in a chromosome 2 YAC sublibrary generated by our experiments. We have identified a minimum of 1610 distinct chromosome 2-specific YACs, which will be a valuable asset for the physical mapping of the second largest human chromosome.

  16. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction.

    PubMed

    Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Neuhausen, Susan L; Ding, Yuan Chun; Rebbeck, Timothy R; Weitzel, Jeffrey N; Lynch, Henry T; Isaacs, Claudine; Ganz, Patricia A; Tomlinson, Gail; Olopade, Olufunmilayo I; Couch, Fergus J; Wang, Xianshu; Lindor, Noralane M; Pankratz, Vernon S; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Viel, Alessandra; Allavena, Anna; Dall'Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I; Zikan, Michal; Claes, Kathleen; Poppe, Bruce; Foretova, Lenka; Mai, Phuong L; Greene, Mark H; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Ozcelik, Hilmi; Andrulis, Irene L; Thomassen, Mads; Gerdes, Anne-Marie; Sunde, Lone; Cruger, Dorthe; Birk Jensen, Uffe; Caligo, Maria; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit; Borg, Ake; Jernström, Helena; Lindblom, Annika; Rantala, Johanna; Stenmark-Askmalm, Marie; Melin, Beatrice; Nathanson, Kate; Domchek, Susan; Jakubowska, Ania; Lubinski, Jan; Huzarski, Tomasz; Osorio, Ana; Lasa, Adriana; Durán, Mercedes; Tejada, Maria-Isabel; Godino, Javier; Benitez, Javier; Hamann, Ute; Kriege, Mieke; Hoogerbrugge, Nicoline; van der Luijt, Rob B; van Asperen, Christi J; Devilee, Peter; Meijers-Heijboer, E J; Blok, Marinus J; Aalfs, Cora M; Hogervorst, Frans; Rookus, Matti; Cook, Margaret; Oliver, Clare; Frost, Debra; Conroy, Don; Evans, D Gareth; Lalloo, Fiona; Pichert, Gabriella; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Hodgson, Shirley; Morrison, Patrick J; Porteous, Mary E; Walker, Lisa; Kennedy, M John; Dorkins, Huw; Peock, Susan; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; de Pauw, Antoine; Mazoyer, Sylvie; Bonadona, Valérie; Lasset, Christine; Dreyfus, Hélène; Leroux, Dominique; Hardouin, Agnès; Berthet, Pascaline; Faivre, Laurence; Loustalot, Catherine; Noguchi, Tetsuro; Sobol, Hagay; Rouleau, Etienne; Nogues, Catherine; Frénay, Marc; Vénat-Bouvet, Laurence; Hopper, John L; Daly, Mary B; Terry, Mary B; John, Esther M; Buys, Saundra S; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F; Dressler, Anne Catharina; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Hansen, Thomas V O; Jønson, Lars; Agnarsson, Bjarni A; Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent; Dutra-Clarke, Ana; Piedmonte, Marion; Rodriguez, Gustavo C; Wakeley, Katie; Boggess, John F; Basil, Jack; Schwartz, Peter E; Blank, Stephanie V; Toland, Amanda Ewart; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y; Gross, Jenny; Schmutzler, Rita; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Lochmann, Magdalena; Arnold, Norbert; Heidemann, Simone; Varon-Mateeva, Raymonda; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Preisler-Adams, Sabine; Kast, Karin; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Aittomäki, Kristiina; Nevanlinna, Heli; Simard, Jacques; Spurdle, Amanda B; Holland, Helene; Chen, Xiaoqing; Platte, Radka; Chenevix-Trench, Georgia; Easton, Douglas F

    2010-12-01

    The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.

  17. A Case of 22q11 Deletion Syndrome (22q11DS) with a Panayiotopoulos Epileptic Pattern: Are Additional Copy-Number Variations a Possible Second Hit in Modulating the 22q11DS Phenotype?

    PubMed Central

    Bertini, Veronica; Valetto, Angelo; Azzarà, Alessia; Legitimo, Annalisa; Saggese, Giuseppe; Consolini, Rita; Orsini, Alessandro; Bonuccelli, Alice

    2017-01-01

    “22q11 deletion syndrome” (22q11DS) is a rare genetic syndrome, in which most patients share the same deletion, but their clinical features may vary a great deal. The genetic mechanisms underlying the variable expressivity and reduced penetrance of 22q11DS still have to be fully elucidated. Epilepsy has been reported in about 15.2% of the patients; however, few studies have focused on this topic, and in most cases, a detailed epileptic profile is missing. Since only a minority of patients experience epileptic seizures, 22q11deletion can be considered a predisposing factor, which is not sufficient “per se” to cause epilepsy; to date, no candidate gene for epilepsy has been identified in the deleted region. We report on a 6-year-old girl with 22q11DS presenting a form of epilepsy that can be classified as “Panayiotopoulos syndrome.” Array CGH revealed an additional microduplication of 172 kb in 2q37, harboring three genes. One of these, DGKD (diacylglycerol kinase delta), is interrupted by the distal breakpoint of the duplication. DGKD encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. This is an important second messenger in a pathway of lipid signaling that has been implicated in epilepsy and other neurological diseases. Disruption of DGKD by a t(X;2) has been previously reported in a patient with epilepsy. The 2q37 microduplication was inherited from her mother, who never experienced epileptic seizures, thus this imbalance is not “per se” sufficient to cause epilepsy. It can be hypothesized that the epileptic phenotype is provoked by the simultaneous presence of 22q11.2 deletion and 2q37 duplication. It has been shown that rare additional copy-number variations (CNVs) outside the 22q11.2 region may modulate the risk of congenital heart defects. It is possible that also for the epileptic phenotype, the additional CNVs may represent an important modifying factor underlying the variable expressivity and

  18. Trends in U.S. Venture Capital Investments Related to Energy: 1980 through the Third Quarter of 2010

    SciTech Connect

    Dooley, James J.

    2010-11-08

    This report documents trends in U.S. venture capital investments over the period 1980 through the third quarter of calendar year 2010 (2010 Q1+Q2+Q3). Particular attention is given to U.S. venture capital investments in the energy/industrial sector over the period 1980-2010 Q1+Q2+Q3 as well as in the more recently created cross-cutting category of CleanTech over the period 1995-2010 Q1+Q2+Q3. During the early 1980s, U.S. venture capital investments in the energy/industrial sector accounted for more than 20% of all venture capital investments. However subsequent periods of low energy prices, the deregulation of large aspects of the energy industry, and the emergence of fast growing new industries like computers (both hardware and software), biotechnology and the Internet quickly reduced the priority accorded to energy/industrial investments. To wit, venture capital investments related to the energy/industrial sector accounted for only 1% of the $132 billion (in real 2010 US$) invested in 2000 by the U.S. venture capital community. The significant increase in the real price of oil that began in 2003-2004 correlates with renewed interest and increased investment by the venture capital community in energy/industrial investment opportunities. Venture capital investments for 2009 for the energy/industrial sector accounted for $2.4 billion or slightly more than 13% of all venture capital invested that year. The total venture capital invested in energy/industrial during the first three quarters of 2010 is close to $2.4 billion accounting for slightly less than 15% of all venture capital investments during the first three quarters of 2010. In 2009, the aggregate amount invested in CleanTech was $2.1 billion (11% of the total US venture capital invested in that lean year) and for the first three quarters of 2010 US venture capital investments in CleanTech have already exceeded $2.8 billion (18% of all US venture capital investments made during the first three quarters of

  19. Correlation between pH dependence of O2 evolution and sensitivity of Mn cations in the oxygen-evolving complex to exogenous reductants.

    PubMed

    Semin, Boris K; Davletshina, Lira N; Rubin, Andrei B

    2015-08-01

    Effects of pH, Ca(2+), and Cl(-) ions on the extraction of Mn cations from oxygen-evolving complex (OEC) in Ca-depleted photosystem II (PSII(-Ca)) by exogenous reductants hydroquinone (H2Q) and H2O2 were studied. Two of 4 Mn cations are released by H2Q and H2O2 at pHs 5.7, 6.5, and 7.5, and their extraction does not depend on the presence of Ca(2+) and Cl(-) ions. One of Mn cations ("resistant" Mn cation) cannot be extracted by H2Q and H2O2 at any pH. Extraction of 4th Mn ion ("flexible" Mn cation) is sensitive to pH, Ca(2+), and Cl(-). This Mn cation is released by reductants at pH 6.5 but not at pHs 5.7 and 7.5. A pH dependence curve of the oxygen-evolving activity in PSII(-Ca) membranes (in the presence of exogenous Ca(2+)) has a bell-shaped form with the maximum at pH 6.5. Thus, the increase in the resistance of flexible Mn cation in OEC to the action of reductants at acidic and alkaline pHs coincides with the decrease in oxygen evolution activity at these pHs. Exogenous Ca(2+) protects the extraction of flexible Mn cation at pH 6.5. High concentration of Cl(-) anions (100 mM) shifts the pH optimum of oxygen evolution to alkaline region (around pH 7.5), while the pH of flexible Mn extraction is also shifted to alkaline pH. This result suggests that flexible Mn cation plays a key role in the water-splitting reaction. The obtained results also demonstrate that only one Mn cation in Mn4 cluster is under strong control of calcium. The change in the flexible Mn cation resistance to exogenous reductants in the presence of Ca(2+) suggests that Ca(2+) can control the redox potential of this cation.

  20. Ataxin-2 Regulates RGS8 Translation in a New BAC-SCA2 Transgenic Mouse Model

    PubMed Central

    Figueroa, Karla P.; Rinehart, Marc D.; Wiest, Shaina; Pflieger, Lance T.; Scoles, Daniel R.; Pulst, Stefan M.

    2015-01-01

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder with progressive degeneration of cerebellar Purkinje cells (PCs) and other neurons caused by expansion of a glutamine (Q) tract in the ATXN2 protein. We generated BAC transgenic lines in which the full-length human ATXN2 gene was transcribed using its endogenous regulatory machinery. Mice with the ATXN2 BAC transgene with an expanded CAG repeat (BAC-Q72) developed a progressive cellular and motor phenotype, whereas BAC mice expressing wild-type human ATXN2 (BAC-Q22) were indistinguishable from control mice. Expression analysis of laser-capture microdissected (LCM) fractions and regional expression confirmed that the BAC transgene was expressed in PCs and in other neuronal groups such as granule cells (GCs) and neurons in deep cerebellar nuclei as well as in spinal cord. Transcriptome analysis by deep RNA-sequencing revealed that BAC-Q72 mice had progressive changes in steady-state levels of specific mRNAs including Rgs8, one of the earliest down-regulated transcripts in the Pcp2-ATXN2[Q127] mouse line. Consistent with LCM analysis, transcriptome changes analyzed by deep RNA-sequencing were not restricted to PCs, but were also seen in transcripts enriched in GCs such as Neurod1. BAC-Q72, but not BAC-Q22 mice had reduced Rgs8 mRNA levels and even more severely reduced steady-state protein levels. Using RNA immunoprecipitation we showed that ATXN2 interacted selectively with RGS8 mRNA. This interaction was impaired when ATXN2 harbored an expanded polyglutamine. Mutant ATXN2 also reduced RGS8 expression in an in vitro coupled translation assay when compared with equal expression of wild-type ATXN2-Q22. Reduced abundance of Rgs8 in Pcp2-ATXN2[Q127] and BAC-Q72 mice supports our observations of a hyper-excitable mGluR1-ITPR1 signaling axis in SCA2, as RGS proteins are linked to attenuating mGluR1 signaling. PMID:25902068

  1. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

    PubMed Central

    Couch, Fergus J.

    2014-01-01

    Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10− 8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10− 4] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10− 9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46–4.70, P = 4.8 × 10− 69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction. PMID:24325915

  2. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction

    PubMed Central

    Antoniou, Antonis C; Beesley, Jonathan; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Neuhausen, Susan L.; Ding, Yuan Chun; Rebbeck, Timothy R.; Weitzel, Jeffrey N.; Lynch, Henry T.; Isaacs, Claudine; Ganz, Patricia A.; Tomlinson, Gail; Olopade, Olufunmilayo I.; Couch, Fergus J.; Wang, Xianshu; Lindor, Noralane M.; Pankratz, Vernon S.; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Viel, Alessandra; Allavena, Anna; Dall’Olio, Valentina; Peterlongo, Paolo; Szabo, Csilla I.; Zikan, Michal; Claes, Kathleen; Poppe, Bruce; Foretova, Lenka; Mai, Phuong L.; Greene, Mark H.; Rennert, Gad; Lejbkowicz, Flavio; Glendon, Gord; Ozcelik, Hilmi; Andrulis, Irene L.; Thomassen, Mads; Gerdes, Anne-Marie; Sunde, Lone; Cruger, Dorthe; Jensen, Uffe Birk; Caligo, Maria; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Dubrovsky, Maya; Cohen, Shimrit; Borg, Ake; Jernström, Helena; Lindblom, Annika; Rantala, Johanna; Stenmark-Askmalm, Marie; Melin, Beatrice; Nathanson, Kate; Domchek, Susan; Jakubowska, Ania; Lubinski, Jan; Huzarski, Tomasz; Osorio, Ana; Lasa, Adriana; Durán, Mercedes; Tejada, Maria-Isabel; Godino, Javier; Benitez, Javier; Hamann, Ute; Kriege, Mieke; Hoogerbrugge, Nicoline; van der Luijt, Rob B; van Asperen, Christi J; Devilee, Peter; Meijers-Heijboer, E.J.; Blok, Marinus J; Aalfs, Cora M.; Hogervorst, Frans; Rookus, Matti; Cook, Margaret; Oliver, Clare; Frost, Debra; Conroy, Don; Evans, D. Gareth; Lalloo, Fiona; Pichert, Gabriella; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary E.; Walker, Lisa; Kennedy, M. John; Dorkins, Huw; Peock, Susan; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; de Pauw, Antoine; Mazoyer, Sylvie; Bonadona, Valérie; Lasset, Christine; Dreyfus, Hélène; Leroux, Dominique; Hardouin, Agnès; Berthet, Pascaline; Faivre, Laurence; Loustalot, Catherine; Noguchi, Tetsuro; Sobol, Hagay; Rouleau, Etienne; Nogues, Catherine; Frénay, Marc; Vénat-Bouvet, Laurence; Hopper, John L.; Daly, Mary B.; Terry, Mary B.; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alex; Goldgar, David; Singer, Christian F.; Dressler, Anne Catharina; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Hansen, Thomas V. O.; Jønson, Lars; Agnarsson, Bjarni A.; Kirchhoff, Tomas; Offit, Kenneth; Devlin, Vincent; Dutra-Clarke, Ana; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Schwartz, Peter E.; Blank, Stephanie V.; Toland, Amanda Ewart; Montagna, Marco; Casella, Cinzia; Imyanitov, Evgeny; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Schmutzler, Rita; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Lochmann, Magdalena; Arnold, Norbert; Heidemann, Simone; Varon-Mateeva, Raymonda; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Preisler-Adams, Sabine; Kast, Karin; Schönbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Aittomäki, Kristiina; Nevanlinna, Heli; Simard, Jacques; Spurdle, Amanda B.; Holland, Helene; Chen, Xiaoqing; Platte, Radka; Chenevix-Trench, Georgia; Easton, Douglas F.

    2010-01-01

    The known breast cancer (BC) susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1,LSP1 and 2q35 confer increased risks of BC for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11 and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for BRCA2 carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for BRCA1 carriers and rs6504950 was not associated with BC for either BRCA1 or BRCA2 carriers. Of the nine polymorphisms investigated, seven were associated with BC for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, p-values:7×10−11-0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e. between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers. PMID:21118973

  3. Mapping of the first preferentially expressed cDNA in human fetal cochlea to human 14q11.2-12 and to a region of homologous synteny on mouse chromosome 12

    SciTech Connect

    Robertson, N.G.; Weremowicz, S.; Kovatch, K.A.

    1994-09-01

    We have isolated a cDNA, Coch-5B2 (D14S564E) from a human fetal cochlear cDNA library by subtractive hybridization and differential screening methods. This is the first cDNA to date shown to be expressed preferentially in human fetal cochlea (membranous labyrinth). On Northern blot of a panel of 14 human fetal tissue RNAs including cochlea, brain, liver, spleen, skeletal muscle, kidney, lung, skin, thymus, adrenal, small intestine, eye, sternal cartilage, and cultured fibroblasts, very high level expression of D14S564E is seen only in cochlea; very faint bands are discernible in brain and eye. Sequence comparison of this clone to sequences in GenBank/EMBL data bases shows no match to any known genes, indicating that it represents a novel cochlear sequence. Chromosome localization of this cochlear cDNA may provide insight into a region of the human genome to which human deafness disorders may map. We have assigned D14S564E to human chromosome 14 using the NIGMS human/rodent somatic cell hybrid mapping panel 1, and regionally to q11.2-q12 by fluorescence in situ hybridization (FISH). Besides detection of the human genomic band on the hybrid panel, genomic bands were seen for mouse and hamster, demonstrating evolutionary conservation of D14S564E. By FISH, signal was detected on human 14q11.2-q12 in 20 metaphases. In 3 metaphases, signal was present on both chromosome 14s. The mouse homolog of this cochlear cDNA was also used to probe human metaphases by FISH: signal was detected in the same region, 14q11.2-12, as the human clone in 5 metaphases, confirming human mapping data and homology to the human cDNA. The human cochlear D14S564E was genetically mapped in the mouse to chromosome 12, in a region of homology with human 14q11.2-q12. This region on mouse 12 contains the asp-1 (audiogenic seizure prone) locus and future studies will be directed at determining whether D14S564E is a candidate gene for this disorder.

  4. Quantitative evaluation of statistical errors in small-angle X-ray scattering measurements

    PubMed Central

    Sedlak, Steffen M.; Bruetzel, Linda K.; Lipfert, Jan

    2017-01-01

    A new model is proposed for the measurement errors incurred in typical small-angle X-ray scattering (SAXS) experiments, which takes into account the setup geometry and physics of the measurement process. The model accurately captures the experimentally determined errors from a large range of synchrotron and in-house anode-based measurements. Its most general formulation gives for the variance of the buffer-subtracted SAXS intensity σ2(q) = [I(q) + const.]/(kq), where I(q) is the scattering intensity as a function of the momentum transfer q; k and const. are fitting parameters that are characteristic of the experimental setup. The model gives a concrete procedure for calculating realistic measurement errors for simulated SAXS profiles. In addition, the results provide guidelines for optimizing SAXS measurements, which are in line with established procedures for SAXS experiments, and enable a quantitative evaluation of measurement errors. PMID:28381982

  5. Unsteady Transonic Flow Past Airfoils in Rigid Body Motion.

    DTIC Science & Technology

    1981-03-01

    weak solutions. The linear theory is deficient in predicting important features of transonic flow outside airfoils in low reduced frequency motion...terms. The term t is substituted n+l adn -i n n+l +n-i by the mean of and , i.e., = 2 = -(u 2 +2uv y+V 2 $ q2 xx xyq 1 2uF v2-2-5 n+l n-I(v2 + 2uvT + 2 ( I...approximate for thie advection equation. Our approximate factorizatio. says that (2) can .) factored as (1+tuQ 14tv )*N - -. tu )(l-.ltvD ) M - 2.’,t (uP DvD Ki

  6. Some nitrogen-14 NMR studies in solids

    SciTech Connect

    Pratum, T.K.

    1983-11-01

    The first order quadrupolar perturbation of the /sup 14/N NMR spectrum yields information regarding the static and dynamic properties of the surrounding electronic environment. Signal to noise problems caused by long /sup 14/N longitudinal relaxation times (T/sub 1/) and small equilibrium polarizations are reduced by rotating frame cross polarization (CP) experiments between /sup 14/N and /sup 1/H. Using quadrupolar echo and CP techniques, the /sup 14/N quadrupolar coupling constants (e/sup 2/qQ/h) and asymmetry parameters (eta) have been obtained for a variety of tetraalkylammonium compounds by observation of their quadrupolar powder patterns at various temperatures. For choline chloride and iodide the /sup 14/N NMR powder patterns exhibit the effects of anisotropic molecular motion, while choline bromide spectra show no such effects.

  7. Analysis of Local Variations in Free Field Seismic Ground Motion.

    DTIC Science & Technology

    1981-01-01

    s )/(sq- k 2) B s (k2 - )/ (sq - k2) - q (k2 _ s 2 )/(sq - 12) -* sk ( s - q)/(sq - k2) (4.32) 102 hee 2 k2 - o2 / 2 2 k2 2 where q 2 , s = k -2 2 /V...JAN Al .J CHEN. J LYSMER. H B SEED DAAG29-76-6-0257 UNCLASSIFIED UCB/EERC-Al/03 ARD-13838.2G 44S IIIJIIL15 fO RtOP f S (OLUTRIN If ,l UN9LASSIFIED...those of the author( s ) and should not be construed as an official Department of the Army Position, policy, or decision, unless so designated by other

  8. Macroscopic Surface Tension in a Lattice Boltzmann BGK Model of Two Immiscible Fluids.

    NASA Astrophysics Data System (ADS)

    Thompson, S. P.; Halliday, I.; Care, C. M.

    1997-08-01

    We present a method by which an interface generating algorithm, similar to that of earlier lattice Boltzmann models of immisible fluids, may be extended to a two component, two-speed D2Q9 lattice Bhatnagar Gross Krook fluid. For two-dimensional, microcurrent-free planar interfaces between the two immiscible fluids we derive expressions for static interfacial tensions and interfacial distributions of the two fluids. Extending our analysis to curved interfaces we propose a scheme for incorporating the influence of interfacial microcurrents which is based upon general symmetry arguments and is correct to second order in lattice velocity. The analysis demonstrates that the interfacial microcurrents have only second order influence upon the macroscopic behaviour of the model. We find good agreement between our calculations and simulation results based on the microcurrent stream function and surface tension results from the pressure tensor or Laplace law.

  9. High quality thin films of thermoelectric misfit cobalt oxides prepared by a chemical solution method

    NASA Astrophysics Data System (ADS)

    Rivas-Murias, Beatriz; Manuel Vila-Fungueiriño, José; Rivadulla, Francisco

    2015-07-01

    Misfit cobaltates ([Bi/Ba/Sr/Ca/CoO]nRS[CoO2]q) constitute the most promising family of thermoelectric oxides for high temperature energy harvesting. However, their complex structure and chemical composition makes extremely challenging their deposition by high-vacuum physical techniques. Therefore, many of them have not been prepared as thin films until now. Here we report the synthesis of high-quality epitaxial thin films of the most representative members of this family of compounds by a water-based chemical solution deposition method. The films show an exceptional crystalline quality, with an electrical conductivity and thermopower comparable to single crystals. These properties are linked to the epitaxial matching of the rock-salt layers of the structure to the substrate, producing clean interfaces free of amorphous phases. This is an important step forward for the integration of these materials with complementary n-type thermoelectric oxides in multilayer nanostructures.

  10. Structure and chromosomal localization of a human water channel (AQP3) gene

    SciTech Connect

    Ishibashi, Kenichi; Sasaki, Sei; Saito, Fumiko

    1995-05-20

    A cDNA encoding rat AQP3, a water channel and a member of the MIP family, that is expressed predominantly in kidney medulla and colon was cloned recently. To determine the structure, tissue distribution, and chromosomal localization of the human AQP3 gene, the authors screened a human kidney cDNA library with rat AQP3 probe and isolated a cDNA coding for human AQP3 protein. The deduced amino acid sequence of human AQP3 was 91% identical to rat AQP3. Human AQP3 mRNA was expressed in colon, kidney, liver, pancreas, lung, peripheral leukocytes, spleen, and prostate. The human AQP3 gene was mapped to 7q36.2-q36.3 by chromosome fluorescence in situ hybridization. 10 refs., 3 figs.

  11. Utility advanced turbine systems (ATS) technology readiness testing and pre-commercial demonstration. Quarterly report, April 1--June 30, 1997

    SciTech Connect

    1997-12-31

    The overall objective of the Advanced Turbine System (ATS) Phase 3 Cooperative Agreement between GE and the US Department of Energy (DOE) is the development of the GE 7H and 9H combined cycle power systems. The major effort will be expended on detail design. Validation of critical components and technologies will be performed including: hot gas path component testing, sub-scale compressor testing, steam purity test trials, and rotational heat transfer confirmation testing. Processes will be developed to support the manufacture of the first system, which will be sited and operated in Phase 4. Technology enhancements that are not required for the first machine design but will be critical for future ATS advances in performance, reliability, and costs will be initiated. Long-term tests of materials to confirm design life predictions will continue. A schematic of the GE H machine is shown. This report summarizes work accomplished in 2Q97.

  12. Truckee Meadows (Reno-Sparks Metropolitan Area) Nevada. Documentation Report

    DTIC Science & Technology

    1983-10-01

    4.oo ROC RESO C RES2 PYRI U)~100 e~X~ "- tm\\ Ow E N ke rlDERY DAk ý95r 2 Q, ~ ~ k~ 41 WAS3110 LAKE -7LE 7, II *. Rec/TR Q Non ~oi 4,01/ -~--Sto CITY...Steamboat Cr. Lske .s.380o TRM KEE outh RIVE -So th Rock /,,-’fru~c ee River Truckee R. Truckee R. .rM v r.. Vistavd0 at Wadsworth at Nixon Overflow 8ver...4400- 4390 -- 4385 ---- _ 4380, . 4375. . ~ -- ____ CD 03106 100+00 90+00 60+0-0 70+0 Horizontal distance in feet ad C= - 4400 CD LAU 4395 436 - --r

  13. Mutations in the embryonal subunit of the acetylcholine receptor (CHRNG) cause lethal and Escobar variants of multiple pterygium syndrome.

    PubMed

    Morgan, Neil V; Brueton, Louise A; Cox, Phillip; Greally, Marie T; Tolmie, John; Pasha, Shanaz; Aligianis, Irene A; van Bokhoven, Hans; Marton, Tamas; Al-Gazali, Lihadh; Morton, Jenny E V; Oley, Christine; Johnson, Colin A; Trembath, Richard C; Brunner, Han G; Maher, Eamonn R

    2006-08-01

    Multiple pterygium syndromes (MPSs) comprise a group of multiple-congenital-anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). In addition, a variety of developmental defects (e.g., vertebral anomalies) may occur. MPSs are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal and nonlethal (Escobar) types. To elucidate the pathogenesis of MPS, we undertook a genomewide linkage scan of a large consanguineous family and mapped a locus to 2q36-37. We then identified germline-inactivating mutations in the embryonal acetylcholine receptor gamma subunit (CHRNG) in families with both lethal and nonlethal MPSs. These findings extend the role of acetylcholine receptor dysfunction in human disease and provide new insights into the pathogenesis and management of fetal akinesia syndromes.

  14. Exponentially Small Splitting and Arnold Diffusion for Multiple Time Scale Systems

    NASA Astrophysics Data System (ADS)

    Procesi, Michela

    We consider the class of Hamiltonians: \\[ \\frac{1}{2}\\sum_{j=1}^{n-1} I_j^2 + \\frac{1}{2} ǎrepsilon I_n^2 + \\frac{p^2}{2} + ǎrepsilon [(cos q - 1) - b^2 (cos 2q - 1)] + ǎrepsilon \\mu f(q) \\sum_{i=1}^n \\sin(\\psi_i) , \\] where 0<= b < (1)/(2), and the perturbing function f(q) is a rational function of eiq. We prove upper and lower bounds on the splitting for such class of systems, in regions of the phase space characterized by one fast frequency. Finally using an appropriate Normal Form theorem we prove the existence of chains of heteroclinic intersections.

  15. Prader-willi syndrome: clinical aspects.

    PubMed

    Elena, Grechi; Bruna, Cammarata; Benedetta, Mariani; Stefania, Di Candia; Giuseppe, Chiumello

    2012-01-01

    Prader-Willi Syndrome (PWS) is a complex multisystem genetic disorder that shows great variability, with changing clinical features during a patient's life. The syndrome is due to the loss of expression of several genes encoded on the proximal long arm of chromosome 15 (15q11.2-q13). The complex phenotype is most probably caused by a hypothalamic dysfunction that is responsible for hormonal dysfunctions and for absence of the sense of satiety. For this reason a Prader-Willi (PW) child develops hyperphagia during the initial stage of infancy that can lead to obesity and its complications. During infancy many PW child display a range of behavioural problems that become more noticeable in adolescence and adulthood and interfere mostly with quality of life. Early diagnosis of PWS is important for effective long-term management, and a precocious multidisciplinary approach is fundamental to improve quality of life, prevent complications, and prolong life expectancy.

  16. SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels.

    PubMed

    Drenth, Joost P H; te Morsche, Rene H M; Guillet, Gerard; Taieb, Alain; Kirby, R Lee; Jansen, Jan B M J

    2005-06-01

    Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm and painful hands, and/or feet. We previously localized the gene for primary erythermalgia to a 7.94 cM region on chromosome 2q. Recently, Yang et al identified two missense mutations of the sodium channel alpha subunit SCN9A in patients with erythermalgia. The presence of voltage-gated sodium channels in sensory neurons is thought to play a crucial role in several chronic painful neuropathies. We examined four different families and two sporadic cases and detected missense sequence variants in SCN9A to be present in primary erythermalgia patients. A total of five of six mutations were located in highly conserved regions. One family with autosomal dominantly inherited erythermalgia was double heterozygous for two separate SCN9A mutations. These data establish primary erythermalgia as a neuropathic disorder and offers hope for treatment of this incapacitating painful disorder.

  17. Equations of Airplane Motion for Large Disturbances from Steady Flight

    DTIC Science & Technology

    1955-05-01

    Squations (21) ~ * ~’( 24 ) Prom zqwtions (16) and (•9j: tantJI1 V 1 YV - tan- 1 W1 SWl + V W, "tU1 + u U1+.V V)W 2 2 , W2 Simplifying and substi’uting ’V...stn i al i- (co1) Cx CLq " sin c - CDq Cosal The v~rJation of’ thrust with airCpeeAi represented by the partial derivative- Tc’M is more conveniently...CWOCDj-lMjCDM-𔃼.q CDq ) coso1 sinai TV Bin TcoB a fu I. (2CS~, + M43CIM +2 qýClq) coo C11 Mu (1cN q *l ’T) cot; a,DU_ SC- l4C, ii Cma sin q nu42 -. 21 c o

  18. A Study of Model Based Maneuvering Controls for Autonomous Underwater Vehicles

    DTIC Science & Technology

    1987-12-01

    y - IX)pq - IXY(p2 -q2 ) - Iz(pr+q) + Ixz(qr-j) + m[XQ(v + ur - wp) -yG(u - r + wq)J 15[(N p + Njrr+Npq pq + Nqr qr Z4[.$Ný v + Nj up + Ný ur + N’q vq...MRR = MWDOT= MQ- ,MVP = MVR = MW = , MV ,MDS = ,MDB = MQN ,MWN = ,MDSN= * YAW HYDRODYNAMIC COEFFICIENTS CONST NPD*T= , NRDOT= NPQ NQR NVDOT= , = ,NR...XG*WO+... A(,)=RHO/2*L**5*NP8*QO + RH/**4JPU+W*OW+. A(65)= IY*PO + IX*PO - 2*IXY*QO - X O+ !4ASS*Y RHO/2*L**5* (NPQ*PO+ NQR *RO) + RHO/2 *L**4*N)Q*VO A

  19. Voigt line infrared atmospheric transmittance calculations by Fourier transform

    NASA Astrophysics Data System (ADS)

    Neuendorffer, A. C.

    1980-04-01

    The absorption coefficient space of an IR atmospheric path contains the linear superposition of many Voigt spectral lines. This paper discusses the practical application of Karp's method to the simulation of satellite transmittance and radiance observations by using fast Fourier transforms on the recursively generated Voigt transforms. Although the procedure is physically straightforward, it is nonetheless computationally demanding and suited primarily to narrow isolated Q-branch regions. Performing the calculation on a 2.4/cm wide 15-micron CO2 Q-branch region demonstrates that 4% of the total absorption takes place above 0.1 mb. This absorption is in the cold mesopause and results in a 1-2% radiation deficit with its inclusion in a satellite radiation calculation.

  20. Department of Defense Survey of Living Conditions Overseas. 1984. Volume 2. Results.

    DTIC Science & Technology

    1985-07-01

    8 8.7 14 Vehicles (shipping, insurance, inspection) 14.7 9 23.0 5 Recreation and entertainment 14.1 10 8.9 13 Family adjustment to the new situation...housing, working conditions, and transportation and least concerned with recreation and entertainment , shopping, medical/dental care, and vehicles...Economy 35.3 52.3 14.7 16.1 20.7 26.0 Half and half 28.2 24.5 24.7 27.6 25.7 26.8 Government 36.6 23.1 60.6 56.3 53.6 47.2 , Q95. Entertainment (theatres

  1. Measurement of R = {sigma}{sub L}/{sigma}{sub T} and the Separated Longitudinal and Transverse Structure Functions in the Nucleon Resonance Region

    SciTech Connect

    Yongguang Liang; Michael Christy; Abdellah Ahmidouch; Christopher Armstrong; John Arrington; Arshak Asaturyan; Steven Avery; O. Baker; Douglas Beck; Henk Blok; C.W. Bochna; Werner Boeglin; Peter Bosted; Maurice Bouwhuis; Herbert Breuer; Daniel Brown; Antje Bruell; Roger Carlini; Jinseok Cha; Nicholas Chant; Anthony Cochran; Leon Cole; Samuel Danagoulian; Donal Day; James Dunne; Dipangkar Dutta; Rolf Ent; Howard Fenker; B. Fox; Liping Gan; Haiyan Gao; Kenneth Garrow; David Gaskell; Ashot Gasparian; Don Geesaman; Ronald Gilman; Paul Gueye; Mark Harvey; Roy Holt; Xiaodong Jiang; Mark Jones; Cynthia Keppel; Edward Kinney; Wolfgang Lorenzon; Allison Lung; David Mack; Pete Markowitz; J.W. Martin; Kevin McIlhany; Daniella Mckee; David Meekins; M.A. Miller; Richard Milner; Joseph Mitchell; Hamlet Mkrtchyan; Robert Mueller; Alan Nathan; Gabriel Niculescu; Maria-Ioana Niculescu; Thomas O'neill; Vassilios Papavassiliou; Stephen Pate; Rodney Piercey; David Potterveld; Ronald Ransome; Joerg Reinhold; E. Rollinde; Oscar Rondon-Aramayo; Philip Roos; Adam Sarty; Reyad Sawafta; Elaine Schulte; Edwin Segbefia; C. Smith; Samuel Stepanyan; Steffen Strauch; Vardan Tadevosyan; Liguang Tang; Raphael Tieulent; Vladas Tvaskis; Alicia Uzzle; William Vulcan; Stephen Wood; Feng Xiong; Lulin Yuan; Markus Zeier; Benedikt Zihlmann; Vitaliy Ziskin

    2004-10-01

    We report on a detailed study of longitudinal strength in the nucleon resonance region, presenting new results from inclusive electron-proton cross sections measured at Jefferson Lab Hall C in the four-momentum transfer range 0.2 < Q{sup 2} < 5.5 GeV{sup 2}. The data have been used to accurately perform over 170 Rosenbluth-type longitudinal/transverse separations. The precision R = {sigma}{sub L}/{sigma}{sub T} data are presented here, along with the first separate values of the inelastic structure functions F{sub 1} and F{sub L} in this regime. The resonance longitudinal component is found to be significant. With the new data, quark-hadron duality is observed above Q{sup 2} = 1 GeV{sup 2} in the separated structure functions independently.

  2. Three-quark light-cone amplitudes of the proton and quark orbital-motion-dependent observables

    NASA Astrophysics Data System (ADS)

    Ji, Xiangdong; Ma, Jian-Ping; Yuan, Feng

    2003-03-01

    We study the three-quark light-cone amplitudes of the proton including quarks' transverse momenta. We classify these amplitudes using a newly-developed method in which light-cone wave functions are constructed from a class of light-cone matrix elements. We derive the constraints on the amplitudes from parity and time-reversal symmetries. We use the amplitudes to calculate the physical observables which vanish when the quark orbital angular momentum is absent. These include transverse-momentum dependent parton distributions Δ qT( x, k⊥), qT( x, k⊥), δq( x, k⊥), and δqL( x, k⊥), twist-three parton distributions gT( x) and hL( x), helicity-flip generalized parton distributions E( x, ξ=0, Q2) and its associates, and the Pauli form factor F2( Q2).

  3. Molecular genetic screening of MBS1 locus on chromosome 13 for microdeletions and exclusion of FGF9, GSH1 and CDX2 as causative genes in patients with Moebius syndrome.

    PubMed

    Uzumcu, Abdullah; Karaman, Birsen; Toksoy, Guven; Uyguner, Z Oya; Candan, Sukru; Eris, Hacer; Tatli, Burak; Geckinli, Bilge; Yuksel, Adnan; Kayserili, Hulya; Basaran, Seher

    2009-01-01

    Moebius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies, and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although some investigations suggested that a causative gene may lie on 13q12.2-q13, there have been no molecular studies targeting possible microdeletions in this region to date. In the present study, we performed microdeletion analyses on 13q12.11-q13 in nine patients, and sequenced three candidate genes in nineteen patients for functional relevance and further resolution of our screening. We ruled out microdeletions on the critical region as a common cause of Moebius syndrome and excluded FGF9, GSH1 and CDX2 genes.

  4. Novel harmonic regularization approach for variable selection in Cox's proportional hazards model.

    PubMed

    Chu, Ge-Jin; Liang, Yong; Wang, Jia-Xuan

    2014-01-01

    Variable selection is an important issue in regression and a number of variable selection methods have been proposed involving nonconvex penalty functions. In this paper, we investigate a novel harmonic regularization method, which can approximate nonconvex Lq  (1/2 < q < 1) regularizations, to select key risk factors in the Cox's proportional hazards model using microarray gene expression data. The harmonic regularization method can be efficiently solved using our proposed direct path seeking approach, which can produce solutions that closely approximate those for the convex loss function and the nonconvex regularization. Simulation results based on the artificial datasets and four real microarray gene expression datasets, such as real diffuse large B-cell lymphoma (DCBCL), the lung cancer, and the AML datasets, show that the harmonic regularization method can be more accurate for variable selection than existing Lasso series methods.

  5. Further Studies of Aerodynamic Loads at Spin Entry

    DTIC Science & Technology

    1977-06-30

    transformation given by the relation da N A n iBn I exp •n(1) nIO •i 38 I d where V- T + iX (2) as illustrated in figure 11. For each point a on the real...in the circle plane is described by the following components: (1) crossflow due to a, W (v) - -iv V sina (10) (2) crosaflow due to 3, W•(v) M - V sin 5...ar -&x sina cosn + 2 co 2 Q(x-x + r0 dr0 /dx3 1 (-)2 +0 031 N rn 2 {[(-Tn) d)n/dx- (A- Xn) dTn/dxX"+ I Mv con l a" n-l• (T - -n) + (N - Xn 22 no~ n

  6. Interstitial duplication of proximal 22q: Phenotypic overlap with cat eye syndrome

    SciTech Connect

    Knoll, J.H.M.; Asamoah, A.; Wagstaff, J.

    1995-01-16

    We describe a child with downslanting palpebral fissures, preauricular malfunctions, congenital heart defect (total anomalous pulmonary venous return), unilateral absence of a kidney, and developmental delay with an apparent interstitial duplication of proximal 22q. Fluorescent in situ hybridization (FISH) analysis showed duplication of the IGLC locus, and C-banding of the duplicated region was negative. The duplication appears to involve 22q11.2-q12. Although the child has neither colobomas nor microphthalmia, he shows phenotypic overlap with with the cat eye syndrome, which is caused by a supernumerary bisatellited chromosome arising from inverted duplication of the short arm and proximal long arm of chromosome 22. Further molecular studies of this patient should help to define the regions responsible for the manifestations of cat eye syndrome. 17 refs., 3 figs., 1 tab.

  7. Mechanical properties of 3D printed warped membranes

    NASA Astrophysics Data System (ADS)

    Kosmrlj, Andrej; Xiao, Kechao; Weaver, James C.; Vlassak, Joost J.; Nelson, David R.

    2015-03-01

    We explore how a frozen background metric affects the mechanical properties of solid planar membranes. Our focus is a special class of ``warped membranes'' with a preferred random height profile characterized by random Gaussian variables h (q) in Fourier space with zero mean and variance < | h (q) | 2 > q-m . It has been shown theoretically that in the linear response regime, this quenched random disorder increases the effective bending rigidity, while the Young's and shear moduli are reduced. Compared to flat plates of the same thickness t, the bending rigidity of warped membranes is increased by a factor hv / t while the in-plane elastic moduli are reduced by t /hv , where hv =√{< | h (x) | 2 > } describes the frozen height fluctuations. Interestingly, hv is system size dependent for warped membranes characterized with m > 2 . We present experimental tests of these predictions, using warped membranes prepared via high resolution 3D printing.

  8. Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

    PubMed Central

    Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

    2016-01-01

    Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

  9. Isolated brachydactyly type E and idiopathic pancreatitis in a patient presenting to a lipid disorders clinic.

    PubMed

    Page, Michael M; Hooper, Amanda J; Glendenning, Paul; Burnett, John R

    2017-04-06

    An 18-year-old female tertiary student was referred to a lipid clinic with hypertriglyceridaemia discovered after presentation with acute pancreatitis. The patient's only medication was l-thyroxine for treatment of hypothyroidism. She was overweight, normotensive, with unremarkable facies. However, she had hypermobile hand joints and brachydactyly resulting in loss of left 3-5 and right 4 and 5 knuckle definitions. Radiography revealed shortening of metacarpals 3-5 on the left and 4 and 5 on the right. Her mother had similar skeletal changes, consistent with a dominant mode of inheritance. Abnormally short digits involving the metacarpals, classified as brachydactyly type E, can be isolated or occur as part of a syndrome. Turner syndrome, Albright hereditary osteodystrophy, hypertension with brachydactyly, chromosome 2q37 microdeletion and PTHLH mutations were excluded following clinical, biochemical and genetic testing. No specific treatment was required. Genetic testing for isolated and syndromic forms of brachydactyly facilitates family screening and prepregnancy counselling.

  10. Stages and Discharges of the Mississippi River and Tributaries and Other Watersheds in the New Orleans District for 1981.

    DTIC Science & Technology

    1981-01-01

    INTERMITTENTLY 10 CAIF, LUMPUTFI) 0AILY. SINCE lAdo . WAHEMkS. .1I,ML~ST, 󈧫.11 FEET UP, MAY 10., 1q27. LCOFSY, 01.70 FOOT ON OICY. 17, 1970. MAXIMUM, JUNE.4 24...RAILROAD HRIJGE AT PILE 2q.5 FROM lEAU . lolA . 03oT60.) , ,. % ,%* IAIE. -414L .LO-T TYPE. * ,LNELRAL p’lFURmATIlUN. GAGE READ ANO MAINTAINED BY NATIONAL...4 %. % 98 DAILY STAGES FCR 1981% LCD LAKE AT MOOR2NGSPCRT, LA.% LOLA TI ON. LAT. 34-41-52, LONG. 93-57-213. FIGh’%AY 530 BRIDOGE. (SYA. 1960024

  11. Ideas and perspectives: climate-relevant marine biologically driven mechanisms in Earth system models

    NASA Astrophysics Data System (ADS)

    Hense, Inga; Stemmler, Irene; Sonntag, Sebastian

    2017-01-01

    The current generation of marine biogeochemical modules in Earth system models (ESMs) considers mainly the effect of marine biota on the carbon cycle. We propose to also implement other biologically driven mechanisms in ESMs so that more climate-relevant feedbacks are captured. We classify these mechanisms in three categories according to their functional role in the Earth system: (1) biogeochemical pumps, which affect the carbon cycling; (2) <q>biological gas and particle shuttles, which affect the atmospheric composition; and (3) biogeophysical mechanisms, which affect the thermal, optical, and mechanical properties of the ocean. To resolve mechanisms from all three classes, we find it sufficient to include five functional groups: bulk phyto- and zooplankton, calcifiers, and coastal gas and surface mat producers. We strongly suggest to account for a larger mechanism diversity in ESMs in the future to improve the quality of climate projections.

  12. Electron loss of fast projectiles in collisions with molecules

    SciTech Connect

    Matveev, V. I.; Makarov, D. N.; Rakhimov, Kh. Yu.

    2011-07-15

    The single- and multiple-electron loss of fast highly charged projectiles in collisions with neutral molecules is studied within the framework of a nonperturbative approach. The cross sections for single-, double-, and triple-electron losses are calculated for the collision system Fe{sup q+}{yields}N{sub 2} (q=24, 25, 26) at the collision energies 10, 100, and 1000 MeV/nucleon. The effects caused by the collision multiplicity and the orientation of the axis of the target molecule are treated. It is shown that the collision multiplicity effect leads to considerable differences for the cases of perpendicular and parallel orientations of the molecular axes with respect to the direction of the projectile motion, while for chaotic orientation such an effect is negligible.

  13. Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: Involvement of the human ERCC2 DNA repair gene

    SciTech Connect

    Flejter, W.L.; McDaniel, L.D.; Johns, D.; Schultz, R.A. ); Friedberg, E.C. )

    1992-01-01

    Cultured cells from individuals afflicted with the genetically heterogeneous autosomal recessive disorder xeroderma pigmentosum (XP) exhibit sensitivity to UV radiation and defective nucleotide excision repair. Complementation of these mutant phenotypes after the introduction of single human chromosomes from repair-proficient cells into XP cells has provided a means of mapping the genes involved in this disease. The authors now report the phenotypic correction of XP cells from genetic complementation group D (XP-D) by a single human chromosome designated Tneo. Detailed molecular characterization of Tneo revealed a rearranged structure involving human chromosomes 16 and 19, including the excision repair cross-complementing 2 (ERCC2) gene from the previously described human DNA repair gene cluster at 19q13.2-q13.3. Direct transfer of a cosmid bearing the ERCC2 gene conferred UV resistance to XP-D cells.

  14. A note for Riesz transforms associated with Schrödinger operators on the Heisenberg Group

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Tang, Guobin

    2017-03-01

    Let H^n be the Heisenberg group and Q=2n+2 be its homogeneous dimension. The Schrödinger operator is denoted by - Δ_{H}^n} + V, where Δ_{H^n} is the sub-Laplacian and the nonnegative potential V belongs to the reverse Hölder class {B_{{q_1}}} for {q_1} ≥Q/2. Let H^p_L(H^n) be the Hardy space associated with the Schrödinger operator for Q/Q+δ _02-Q/q_1}. In this note we show that the operators {T_1} = V{( - Δ_{H^n} + V)^{ - 1}} and {T_2} = {V^{1/2}}{( - Δ _{H^n} + V)^{ - 1/2}} are bounded from H_L^p(H^n) into {L^p}(H^n). Our results are also valid on the stratified Lie group.

  15. Optimization of Potent Inhibitors of P. falciparum Dihydroorotate Dehydrogenase for the Treatment of Malaria

    PubMed Central

    2011-01-01

    Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure–activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug–drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)-N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate. PMID:24900364

  16. A Chinese patient with KBG syndrome and a 9q31.2-33.1 microdeletion.

    PubMed

    Xu, Mingzhi; Zhou, Huali; Yong, Jing; Cong, Peikuan; Li, Chengjiang; Yu, Yunsong; Qi, Ming

    2013-05-01

    KBG syndrome is characterized by postnatal short stature, macrodontia, facial and hand anomalies, delayed bone age and intellectual disability. KBG syndrome is an infrequently reported autosomal dominant condition caused by a mutation or haploinsufficiency of ANKRD11 at 16q24.3. We report on a patient, who showed many manifestations of KBG syndrome and was found to harbor a de novo ANKRD11 mutation, c.362T > A (p.Met121Lys). As the patient showed additional characteristics not occurring in KBG syndrome, a CGH array was performed which showed a de novo microdeletion of 9q31.2-q33.1. The majority of findings in our patient can be explained by the combined ANKRD11 mutation and 9q31.2-33.1 deletion. The case demonstrates well the need for comparing an abnormal genotype with a detailed phenotype analysis and the need for further studies in case the phenotype is unusual for the genotype.

  17. Interstitial deletion of 11q-implicating the KIRREL3 gene in the neurocognitive delay associated with Jacobsen syndrome.

    PubMed

    Guerin, Andrea; Stavropoulos, Dimitri J; Diab, Yaser; Chénier, Sébastien; Christensen, Hilary; Kahr, Walter H A; Babul-Hirji, Riyana; Chitayat, David

    2012-10-01

    Jacobsen syndrome (JS) is a rare contiguous gene disorder characterized by a deletion within the distal part of the long arm of chromosome 11 ranging in size from 7 to 20 Mb. The clinical findings include characteristic dysmorphic features, growth and psychomotor delays and developmental anomalies involving the brain, eyes, heart, kidneys, immune, hematologic, endocrine, and gastrointestinal systems. The majority of cases are due to a terminal deletion of 11q; however interstitial deletions have also been reported. We report on a child with clinical manifestations consistent with JS who had a 2.899 Mb interstitial deletion at 11q24.2-q24.3 which is the smallest interstitial deletion reported so far to our knowledge. This deletion includes the KIRREL3 gene, and given our patient's history of neurocognitive delay and autism spectrum disorder, it raises the possibility that this gene is a candidate for the social and expressive language delay observed in our patient.

  18. Physical Principles of Skeletal Minerals Revealed with Spectromicroscopy

    SciTech Connect

    Gilbert, Pupa

    2009-08-05

    Skeletal elements of marine and terrestrial organisms have the most fascinating nano-to-macro-structures, attracting the attention of physicists, biologists, chemists, and materials scientists. Using X-PEEM spectromicroscopy we revealed some of the fundamental mechanisms leading to the formation of these biominerals. Specifically, we addressed the following questions and provided the answers: 1Q) How do teeth, bones, and echinoderm and mollusk shells acquire their unusual, curved and complex morphology, if they are composed of single crystals? 1A) Via amorphous precursor phases; 2Q) How does crystallinity propagate through the amorophous precursor phases in sea urchin spicules and teeth? 2A) By secondary nucleation, following random walk patterns; 3Q) How does iridescent mother-of-pearl become ordered? 3A) Gradually, through a kinetic mechanisms in which fastest growing single-crystals win the competition for space, thus end up being approximately co-oriented.

  19. Prader-Willi syndrome.

    PubMed

    Cassidy, Suzanne B; Driscoll, Daniel J

    2009-01-01

    Prader-Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect.

  20. Electron Distributions in Hexagonal Selenium and Tellurium and Monoclinic Selenium with Dilute Impurities and Associated Nuclear Quadrupole Interactions*.

    NASA Astrophysics Data System (ADS)

    Maharjan, N. B.; Paudyal, D. D.; Mishra, D. R.; Byahut, S.; Aryal, M. M.; Cho, Hwa-Suck; Scheicher, R. H.; Chow, Lee; Jeong, Junho; Das, T. P.

    2006-03-01

    The electron structures of Selenium chains and rings with Te impurities in hexagonal and monoclinic structures respectively and Se impurities in Te chains in hexagonal lattice have been studied using Hartree-Fock cluster model including many-body effects, including lattice relaxation effects. The calculated electronic wave-functions are utilized to obtain ^77Se and ^125Te nuclear quadrupole coupling constants e^2qQ and asymmetry parameters η and compared with available experimental data from Mossbauer and perturbed angular correlation measurements. From our results, the expected nature of nuclear quadrupole interactions associated with Sb impurities will be discussed. *Supported by NSF US-Nepal Program and UGC Nepal **Also at UCF, Orlando