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Sample records for reli sso hla-drb

  1. HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1.

    Science.gov (United States)

    van Gerven, N M F; de Boer, Y S; Zwiers, A; Verwer, B J; Drenth, J P H; van Hoek, B; van Erpecum, K J; Beuers, U; van Buuren, H R; den Ouden, J W; Verdonk, R C; Koek, G H; Brouwer, J T; Guichelaar, M M J; Vrolijk, J M; Coenraad, M J; Kraal, G; Mulder, C J J; van Nieuwkerk, C M J; Bloemena, E; Verspaget, H W; Kumar, V; Zhernakova, A; Wijmenga, C; Franke, L; Bouma, G

    2015-06-01

    The classical human leukocyte antigen (HLA)-DRB1*03:01 and HLA-DRB1*04:01 alleles are established autoimmune hepatitis (AIH) risk alleles. To study the immune-modifying effect of these alleles, we imputed the genotypes from genome-wide association data in 649 Dutch AIH type-1 patients. We therefore compared the international AIH group (IAIHG) diagnostic scores as well as the underlying clinical characteristics between patients positive and negative for these HLA alleles. Seventy-five percent of the AIH patients were HLA-DRB1*03:01/HLA-DRB1*04:01 positive. HLA-DRB1*03:01/HLA-DRB1*04:01-positive patients had a higher median IAIHG score than HLA-DRB1*03:01/HLA-DRB1*04:01-negative patients (P<0.001). We did not observe associations between HLA alleles and alanine transaminase levels (HLA-DRB1*03:01: P=0.2; HLA-DRB1*04:01; P=0.5); however, HLA-DRB1*03:01 was independently associated with higher immunoglobulin G levels (P=0.04). The HLA-DRB1*04:01 allele was independently associated with presentation at older age (P=0.03) and a female predominance (P=0.04). HLA-DRB1*03:01-positive patients received immunosuppressive medication and liver transplantation. In conclusion, the HLA-DRB1*03:01 and HLA-DRB1*04:01 alleles are both independently associated with the aggregate diagnostic IAIHG score in type-1 AIH patients, but are not essential for AIH development. HLA-DRB1*03:01 is the strongest genetic modifier of disease severity in AIH.

  2. The Protective Role of HLA-DRB1∗13 in Autoimmune Diseases

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    Bettencourt, Andreia; Carvalho, Cláudia; Leal, Bárbara; Brás, Sandra; Lopes, Dina; Martins da Silva, Ana; Santos, Ernestina; Torres, Tiago; Almeida, Isabel; Farinha, Fátima; Barbosa, Paulo; Marinho, António; Selores, Manuela; Correia, João; Vasconcelos, Carlos; Costa, Paulo P.; da Silva, Berta Martins

    2015-01-01

    Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB1∗15 (OR = 2.17) and HLA-DRB1∗03 (OR = 1.81) alleles with MS, HLA-DRB1∗03 with SLE (OR = 2.49), HLA-DRB1∗01 (OR = 1.79) and HLA-DRB1∗04 (OR = 2.81) with RA, HLA-DRB1∗07 with Ps + PsA (OR = 1.79), HLA-DRB1∗01 (OR = 2.28) and HLA-DRB1∗08 (OR = 3.01) with SSc, and HLA-DRB1∗03 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB1∗13 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB1∗13 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB1∗13, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB1∗13 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection. PMID:26605347

  3. HLA-A, HLA-B, and HLA-DRB1 Allele and Haplotype Frequencies in Renal Transplant Candidates in a Population in Southern Brazil.

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    Saito, Patrícia Keiko; Yamakawa, Roger Haruki; Noguti, Erika Noda; Bedendo, Gustavo Borelli; Júnior, Waldir Veríssimo da Silva; Yamada, Sérgio Seiji; Borelli, Sueli Donizete

    2016-05-01

    Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates. The frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Paraná State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or "pardos"] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology. In the analysis of the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA-A*02 (25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07-DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68, B*08, and B*58 allele frequencies among ethnic groups. This study provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil. © 2015 Wiley Periodicals, Inc.

  4. HLA-DRB1 among patients with Vogt-Koyanagi-Harada disease in Saudi Arabia.

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    Iqniebi, Alia; Gaafar, Ameera; Sheereen, Atia; Al-Suliman, Abdullah; Mohamed, Gamal; Al-Hussein, Khaled; Tabbara, Khalid F

    2009-09-12

    Vogt-Koyanagi-Harada (VKH) disease is an immune-mediated disorder with autoimmune insult directed against antigens associated with melanocytes. The genetic predisposition among VKH has not been explored in Saudi Arabia. So, the purpose of this study was to investigate the association of human leukocyte antigen (HLA)-DRB1 alleles to VKH patients and to clarify the molecular genetic mechanism underlying the susceptibility or resistance to VKH disease. Genomic DNA from a total of 30 patients with VKH and 29 control subjects was extracted from peripheral blood, and HLA-DRB1 alleles were typed by polymerase chain reaction and sequence based typing (SBT). We found a statistically significant difference in the prevalence of HLA-DRB1 *0405 between the VKH patients and control subjects (p<0.05). Eleven out of thirty (36.6%) patients with VKH had positive HLA-DRB1 *0405 compared to two out of twenty-nine (6.9%) control subjects. However, there were no statistically significant differences in the HLA-DRB1 alleles *01, *0101, *0102, *0301, *04, *0403, *0404, *0701, *1001, *1101, *1112, *1301, *1302, *1303, *1501, and *1502 between the VKH patients and controls. Patients with VKH had significantly greater incidence of HLA-DRB1 *0405 when compared to age and sex-matched controls. Consequently, this finding suggests that HLA-DRB1 *0405 allele might play a role in the pathogenesis of VKH disease.

  5. Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

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    Florencia del Puerto

    Full Text Available BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG, and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD, and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

  6. Combination of interleukin-10 gene promoter polymorphisms with HLA-DRB1*15 allele is associated with multiple sclerosis

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    Majid Shahbazi

    2017-01-01

    Interpretation & conclusions: The IL-10 and HLA-DRB1*15 polymorphisms were associated with the susceptibility to MS in Iranian patients. Our results suggest that gene-gene interaction of IL-10 polymorphisms and HLA-DRB1*15 alleles may be important factors in the development of MS.

  7. HLA-DRB*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis.

    Science.gov (United States)

    Yaldizli, Özgür; Sethi, Varun; Pardini, Matteo; Tur, Carmen; Mok, Kin Y; Muhlert, Nils; Liu, Zheng; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Yousry, Tarek A; Houlden, Henry; Hardy, John; Miller, David H; Chard, Declan T

    2016-05-01

    The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. To assess HLA-DRB(*)1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB(*)1501 haplotype was determined by genotyping (rs3135388). No significant differences were observed in MRI measures between the HLA-DRB(*)1501 subgroups. The HLA-DRB(*)1501 haplotype is not strongly associated with MRI-visible grey matter pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, T.R.; Rostgaard, K.; Askling, J.

    2009-01-01

    BACKGROUND: Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known. OBJECTIVE: To assess...

  9. Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

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    Kwangwoo Kim

    Full Text Available The genetic association of HLA-DRB1 with rheumatoid arthritis (RA and systemic lupus erythematosus (SLE is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5 has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.

  10. HLA-DRB1 allele association with rheumatoid arthritis susceptibility and severity in Syria.

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    Mourad, Jamil; Monem, Fawza

    2013-02-01

    Rheumatoid arthritis (RA) is a complex multifactorial chronic disease. The importance of human leukocyte antigen as a major genetic risk factor for RA was studied worldwide. Although it is widely distributed in different Syrian areas, studies of human leukocyte antigen (HLA) alleles' role are absent. The aim of our study was to determine the association of HLA-DRB1 alleles with the susceptibility and severity of RA in Syria. Eighty-six RA patients and 200 healthy controls from Syria were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP antibodies were measured by ELISA. Rheumatoid factor (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS-28) values were obtained from patients' medical records. DAS-28 was used to assess the clinical severity of the patients. The HLA-DRB1*01, *04, and *10 frequencies showed a strong association with the disease susceptibility (OR = 2.29, 95% CI = 1.11-4.75, P = 0.022; OR = 3.16, 95% CI = 2.0 -4.8, P < 0.0001; OR = 2.43, 95% CI = 1.07-5.51, P = 0.029 respectively), while the frequencies of HLA-DRB1*11, and *13 were significantly lower in RA patients than in controls (OR = 0.49, 95% CI = 0.3-0.8, P = 0.004; OR = 0.32, 95% CI = 0.15-0.69, P = 0.002, respectively). The other HLA-DRB1 alleles showed no significant difference. The frequency of anti-CCP antibodies was higher in shared epitope (SE) positive patients compared with SE-negative patients (OR = 5.5, 95% CI = 2-15.1, P = 0.00054). DAS-28 of RA patients didn't show significant difference between the SE negative and the SE positive groups. Our results indicate that HLA-DRB1*01, *04, and *10 alleles are related with RA, while HLA-DRB1*11 and *13 protect against RA in the Syrian population.

  11. HLA DRB5*01 Association Survey with Multiple Sclerosis in Khuzestan Province of Iran

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    Tahereh Latifi Pakdehi

    2017-08-01

    Full Text Available Background Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system (CNS. Although the cause of MS is currently unknown, both genetic and environmental factors have been shown to contribute to the pathogenesis of MS. The human leukocyte antigen (HLA class II alleles DRB1*1501, DRB5*0101, DQA1*0102, DQB1*0602 may have an important genetic effect. However, this is controversial in different population studies. Objectives The aim of this study was to investigate the correlation of HLA DRB5*01 with MS in Khuzestan province. Methods The present case-control study focused on HLA DRB5*01 association in 202 MS patients from Khuzestan. Seventy four point two five percent (74.25% of patients classified as relapsing-remitting and other patients were as primary-progressive, secondary progressive and progressive-relapsing MS. One hundred eighty seven persons that have no any inflammatory diseases investigated as control group. Polymerase chain reaction amplification method was performed to determine the type of HLA with sequence-specific primers (PCR-SSP. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 21 statistical software and the chi square test. Results Twenty- seven point seven two percent (27.72% of patients and 21.39% from the control group were positive with this type of HLA. Conclusions This is the first study that investigate HLA DRB5*01 association with multiple sclerosis patients in Khuzestan. We found that there is no association between HLA DRB5*01 with multiple sclerosis in Khuzestan province (P = 0.148.

  12. HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity

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    Salvarani, C.; Boiardi, L.; Mantovani, V.; Ranzi, A.; Cantini, F.; Olivieri, I.; Bragliani, M.; Collina, E.; Macchioni, P.

    1999-01-01

    OBJECTIVE—To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
METHODS—A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
RESULTS—No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).
CONCLUSION—These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.

 PMID:10225816

  13. [Interaction between HLA-DRB1 gene polymorphism and environmental risk factors in the development of gestational diabetes mellitus].

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    Wang, Ming; Zhang, Li; Liu, Xinghui

    2014-04-01

    To explore the interactions between human leukocyte antigen (HLA) -DRB1 gene polymorphism and environmental risk factors in gestational diabetes mellitus (GDM) pathogenesis. Pregnant women who had prenatal cares in Obstetric Department, West China Second Hospital of Sichuan University were recruited from January 1(st) to December 31(st) in 2011. A prospective cohort study was conducted in the women who had a glucose challenge test (GCT) or 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks. A total of 104 women diagnosed with GDM were randomly included in GDM group while another 103 normal women fell into the control group. The HLA-DRB1 polymorphism was detected by Polymerase Chain Reaction - Sequence Specific Primers (PCR-SSP) method in both groups. The interactions between HLA-DRB1 polymorphism and environmental risk factors were analyzed based on the simple-case-study method. (1) There were 712 pregnant women with complete perinatal information during January 1(st) to December 31(st) , 2011, among whom 175 (24.6%) women were diagnosed with GDM. A logistic regression analysis showed that advanced maternal age (OR = 1.081, 95%CI: 1.027- 1.138), imbalanced diet (OR = 3.329, 95%CI: 2.167-5.116), high body mass index (BMI ≥ 24.0 kg/m(2)) before pregnancy (OR = 1.095, 95%CI:1.008-1.190), HBsAg carrier status (OR = 3.173, 95%CI: 1.387-7.260) and family history of diabetes mellitus (DM) (OR = 1.798, 95%CI: 1.063-3.041) were risk factors of GDM. (2) There were 49 HLA-DRB1 genotypes and 51 HLA-DRB1 genotypes in GDM group and the control group, respectively. We further compared the genotypes that occurred in over 3 cases in either group and found that HLA-DRB1*12, 16 was only detected in 5 cases (5/103, 4.9%) in control group, and the difference was significant between the two groups (P = 0.029). HLA-DRB1*11, 16 and HLA-DRB1*09,09 were only detected in 4 cases (3.8%, 4/104) and 5 cases (4.8%, 5/104) in GDM group respectively, but without significant

  14. Susceptibility to aplastic anemia is associated with HLA-DRB1*1501 in an aboriginal population in Sabah, Malaysia.

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    Dhaliwal, J S; Wong, Lily; Kamaluddin, Muhammad Amir; Yin, Lee Yin; Murad, Shahnaz

    2011-10-01

    The incidence of aplastic anemia is reported to be higher in Asia than elsewhere. We studied the frequency of human leukocyte antigen (HLA) DRB1 alleles in aplastic anemia patients from 2 genetically similar aboriginal groups, the Kadazan and the Dusun, and compared them with genetically matched community and hospital controls. HLA-DRB1*15 was significantly higher in the patients compared with controls (p = 0.005), confirming similar findings in Japanese and Caucasian studies. Further testing indicated a significantly higher frequency of HLA-DRB1*1501 in patients compared with controls (p = 0.0004) but no significant difference in the frequency of HLA-DRB1*1502. The high frequency of HLA-DRB1*15 in the Kadazan and Dusun population combined with the wide variety of environmental factors associated with aplastic anemia could be the reason for the elevated incidence of aplastic anemia in the Kadazan and Dusun in Sabah. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  15. Influence of HLA-DRB1* incompatibility on the occurrence of rejection episodes and graft survival in serologically HLA-DR-matched renal transplant combinations

    NARCIS (Netherlands)

    Lardy, N. M.; van der Horst, A. R.; ten Berge, I. J.; Surachno, S.; Wilmink, J. M.; de Waal, L. P.

    1997-01-01

    BACKGROUND: The aim of the present study was to analyze the effect of HLA-DRB1* mismatches on graft function and graft survival in 92 patients who received serologically HLA-DR split antigen-matched cadaveric renal transplants. METHODS: The polymorphic second exon of the HLA-DRB1 alleles was typed

  16. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

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    Urrutia, Inés; Martínez, Rosa; López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

    2017-01-01

    The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively. The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  17. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY.

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    Inés Urrutia

    Full Text Available The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY.160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4; 1 risk allele (DR3 or DR4; 2 risk alleles (DR3 and/or DR4.Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6 and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96 and OR 0.06 (95% CI: 0.02-0.18, respectively.The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4 reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

  18. HLA-DRB and HLA-DQ genetic variability in patients with aspirin-exacerbated respiratory disease.

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    Esmaeilzadeh, Hossein; Nabavi, Mohammad; Amirzargar, Ali Akbar; Aryan, Zahra; Arshi, Saba; Bemanian, Mohammad Hassan; Fallahpour, Morteza; Mortazavi, Negar; Rezaei, Nima

    2015-01-01

    Major histocompatibility complex (MHC) class II is involved in T-cell activation, cytokine secretion, and induction of immune responses. Cytokines, staphylococcus super antigens, and eosinophil activation are proposed to play important roles in aspirin-exacerbated respiratory disease (AERD). This study is aimed at investigating the association of HLA-DRB and DQ genetic variabilities in patients with AERD. A genetic association analysis in three different groups, including 33 patients with AERD, 17 patients with aspirin-tolerant asthma (ATA), and 100 healthy controls was performed. Oral aspirin challenge (OAC) test was performed to identify aspirin hypersensitivity. Pulmonary function test (PFT) was performed for all patients. Eosinophil percentage in nasal smear and peripheral blood and serum immunoglobin (Ig)E were investigated. HLA-DRB, HLA-DQA1, and HLA-DQB1 were genotyped using polymerase chain reaction. HLA-DQB1*0302 (OR, 5.49, 95% confidence interval [CI],(2.40-12.59)), HLA-DQA1*0301 (OR, 2.90, 95% CI, (1.49-5.67)), HLA-DRB4 (OR, 2.94, 95% CI, (1.61-5.36)), and HLA-DRB1*04 (OR, 3.19, 95% CI, (1.57-6.47)) were higher in patients with AERD compared with controls. In patients with AERD, HLA-DQB1*0301 (OR,0.22, 95% CI, (0.09-0.54)), HLA-DQA1*0501 (OR, 0.42, 95% CI, (0.21-0.81)), HLA-DRB1*11 (OR, 0.30, 95% CI, (0.12-0.73)), and HLA-DRB3 (OR, 0.38, 95% CI, (0.21-0.70)) were significantly lower compared with healthy controls. Patients with AERD had lower frequencies of HLA-DQB1*0301 (OR, 0.27, 95% CI, (0.08-0.86)), and HLA-DRB1*011 (OR, 0.27, 95% CI, (0.08-0.86)) compared with ATA. Haplotypes of HLA-DRB1*04/ DQA1*0301/ DQB1*0302 (OR, 4.25, 95% CI, (1.94-9.29)) and HLA-DRB1*07 /DQA1*0201/ DQB1*0201 (OR, 3.52, 95% CI, (1.54-8.06)) were higher in patients with AERD compared with controls (all p < 0.05). Results of this study suggest that HLA-DQB1*0302 and HLA-DRB1*04 and their related haplotypes are genes involved in predisposing patients to AERD, whereas HLA-DQB1

  19. HLA-DRB1 alleles in four Amerindian populations from Argentina and Paraguay

    Science.gov (United States)

    2009-01-01

    The major histocompatibility complex (MHC) is one of the biological systems of major polymorphisms. The study of HLA class II variability has allowed the identification of several alleles that are characteristic to Amerindian populations, and it is an excellent tool to define the relations and biological affinities among them. In this work, we analyzed the allelic distribution of the HLA-DRB1 class II locus in four Amerindian populations: Mapuche (n = 34) and Tehuelche (n = 23) from the Patagonian region of Argentina, and Wichi SV (n = 24) and Lengua (n = 17) from the Argentinean and Paraguayan Chaco regions, respectively. In all of these groups, relatively high frequencies of Amerindian HLA-DRB1 alleles were observed (DRB1*0403, DRB1*0407, DRB1*0411, DRB1*0417, DRB1*0802, DRB1*0901, DRB1*1402, DRB1*1406 and DRB1*1602). However, we also detected the presence of non-Amerindian variants in Mapuche (35%) and Tehuelche (22%). We compared our data with those obtained in six indigenous groups of the Argentinean Chaco region and in a sample from Buenos Aires City. The genetic distance dendrogram showed a clear-cut division between the Patagonian and Chaco populations, which formed two different clusters. In spite of their linguistic differences, it can be inferred that the biological affinities observed are in concordance with the geographic distributions and interethnic relations established among the groups studied. PMID:21637670

  20. Chronic cerebrospinal vascular insufficiency is not associated with HLA DRB1*1501 status in multiple sclerosis patients.

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    Bianca Weinstock-Guttman

    Full Text Available BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS. The objective was to assess the associations between HLA DRB1*1501 status and the occurrence of CCSVI in MS patients. METHODOLOGY/PRINCIPAL FINDINGS: This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD study. The HLA DRB1*1501 status was obtained in 268 MS patients and 155 controls by genotyping rs3135005, a SNP associated with DRB1*1501 status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52, p<0.001 in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of HLA DRB1*1501 positivity (HLA(+ in MS was higher compared (OR = 2.33, p<0.001 to 31.6% to controls. The HLA(+ frequency in the non-progressive (51.6% and progressive MS groups (52.3% was similar. The frequency of HLA(+ CCSVI(+ was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of HLA DRB1*1501 status in MS patients. CONCLUSIONS/SIGNIFICANCE: The lack of strong associations of CCSVI with HLA DRB1*1501 suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS.

  1. PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

    Science.gov (United States)

    Hisa, Kaori; Yanagimachi, Masakatsu D; Naruto, Takuya; Miyamae, Takako; Kikuchi, Masako; Hara, Rhoki; Imagawa, Tomoyuki; Yokota, Shumpei; Mori, Masaaki

    2017-01-01

    Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA). Many studies have reported that both a 'shared epitope' (SE) encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4) gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA. JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic) and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs), rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays. Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001). No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA)-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03). PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

  2. PADI4 and the HLA-DRB1 shared epitope in juvenile idiopathic arthritis.

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    Kaori Hisa

    Full Text Available Both genetic and environmental factors are associated with susceptibility to juvenile idiopathic arthritis (JIA. Many studies have reported that both a 'shared epitope' (SE encoded by several HLA-DRB1 alleles and the peptidyl arginine deiminase type 4 (PADI4 gene polymorphisms are associated with susceptibility to rheumatoid arthritis (RA. However, it is uncertain whether JIA and RA share the latter genetic risk factor. Therefore, here we investigated relationships between HLA-SE and PADI4 polymorphisms with clinical subtypes of JIA.JIA patients (39 oligoarthritis, 48 RF-positive polyarthritis, 19 RF-negative polyarthritis and 82 systemic and 188 healthy controls were genotyped for HLA-DRB1 by PCR-sequence-specific oligonucleotide probe methodology. Three PADI4 gene single nucleotide polymorphisms (SNPs, rs2240340, rs2240337 and rs1748033, were genotyped using TaqMan SNP Genotyping Assays.Frequencies of the HLA-SE were higher in RF-positive polyarticular JIA than in healthy controls. RF-positive polyarticular JIA was associated with HLA-SE (OR = 5.3, 95% CI = 2.5-11.9, pc < 0.001. No associations were found between clinical subtypes of JIA and PADI4 allele frequency. Nonetheless, rs2240337 in the PADI4 gene was significantly associated with anti-cyclic citrullinated peptide antibody (ACPA-positivity in JIA. The A allele at rs2240337 was a significant risk factor for ACPA positivity in JIA (OR = 5.6, 95% CI = 1.71-23.7 pc = 0.03.PADI4 gene polymorphism is associated with ACPA-positivity in JIA. The association of HLA-SE with RF-positive polyarticular JIA as well as RA is confirmed in Japanese. Thus, HLA-SE and PADI4 status both influence JIA clinical manifestations.

  3. HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population.

    Science.gov (United States)

    Konda Mohan, Vasanth; Ganesan, Nalini; Gopalakrishnan, Rajasekhar; Venkatesan, Vettriselvi

    2017-10-01

    To investigate the presence of the 'shared epitope' (SE) in the HLA-DRB1 alleles in patients with RA and to ascertain the frequency of the HLA-DRB1 alleles with autoantibodies (anti-cyclic citrullinated peptide [anti-CCP] rheumatoid factor [RF]) and disease severity. A total of 200 RA patients and 200 apparently healthy subjects participated in the study. HLA-DRB1 were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP and RF in serum were determined by in vitro quantitative enzyme-linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score-28 (DAS-28). Chi-square test and Student's t-test were used in the statistical analysis. A significant increase in the frequency of HLA-DRB1*01, *04, *10 and *14 were identified in RA patients and showed a strong association with the disease susceptibility. While the frequencies of HLA-DRB1*03, *07, *11 and *13 were significantly lower in RA patients than in controls. The other HLA-DRB1 alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti-CCP and RF antibodies did not showed significant difference in SE-positive patients compared with SE-negative patients. DAS-28 values of RA patients showed no significant difference between SE-positive and SE-negative groups. Our results indicate that HLA-DRB1*01, *04, *10 and *14 alleles are related with RA, while HLA-DRB1*03, *07, *11 and *13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  4. Frequency determination of HLA-DRB1 and HLA-DQB1 alleles in children with primary vesicoureteral reflux

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    Mohammadreza Bazrafshani

    2014-12-01

    Conclusion: The HLA cluster might affect on susceptibility to vesicoureteral reflux es-pecially by locus which located close to HLA-DRB1 and HLA-DQB1 genes. This study demonstrates for the first time in Iran. However, further extensive researches with a large number of samples from different populations and ethnicities are required to val-idate the results obtained in this study.

  5. Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in Inhabitants of Astana, the Capital City of Kazakhstan

    Science.gov (United States)

    Kuranov, Alexandr B.; Vavilov, Mikhail N.; Abildinova, Gulshara Zh.; Akilzhanova, Ainur R.; Iskakova, Aisha N.; Zholdybayeva, Elena V.; Boldyreva, Margarita N.; Müller, Claudia A.; Momynaliev, Kuvat T.

    2014-01-01

    Background Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations. Methodology/Principal Findings A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians. Conclusions/Significance The HLA-DRB1, -DQA1and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations. PMID:25531278

  6. Analysis of HLA-A, HLA-B, HLA-DRB1 allelic, genotypic, and haplotypic frequencies in colombian population

    OpenAIRE

    Yazmin Rocío Árias-Murillo; Miguel Ángel Castro-Jiménez; María Fernanda Ríos-Espinosa; Juan Javier López-Rivera; Sandra Johanna Echeverry-Coral; Oscar Martínez-Nieto

    2010-01-01

    Introduction: The high polymorphism of the HLA system allows its typification to be used as valuable tool in establishing association to various illnesses, immune and genetic profiles; it also provides a guide to identifying compatibility among donors and receptors of organs transplants. Objective: To establish HLA-A, HLA-B, and HLA.DRB1 allele, genotype and haplotype frequencies among patients treated at Clinica Colsanitas SA. Methods: 561 patients coming from different regions in Col...

  7. Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in inhabitants of Astana, the capital city of Kazakhstan.

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    Alexandr B Kuranov

    Full Text Available BACKGROUND: Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA genes at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations. METHODOLOGY/PRINCIPAL FINDINGS: A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS. Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%, HLA-DQA1*03:01 (13.1% and HLA-DQB1*03:01 (17.6%. In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0% was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians. CONCLUSIONS/SIGNIFICANCE: The HLA-DRB1, -DQA1 and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations.

  8. Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients.

    Science.gov (United States)

    Farouk, H M; Mansour, H E; Rahman, S A; Mostafa, A A; Shamy, H A; Zarouk, W A

    2009-09-01

    Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

  9. Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

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    H.M. Farouk

    2009-09-01

    Full Text Available Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%. RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3% and HLA-DRB1*04 alleles (83.3%. Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05. HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

  10. Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

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    Nisell Magnus

    2010-02-01

    Full Text Available Abstract Background A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping. Subjects and methods In this study we HLA typed a large patient population (n = 754 recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS (n = 302 and those without (non-Löfgren's (n = 452, and the majority of them were clinically classified into those with recovery within two years (resolving and those with signs of disease for more than two years (non-resolving. PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366 served as controls. Results There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10-36. Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis dominated over that of DRB1*15 (bad prognosis. Conclusions We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.

  11. Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA-DRB1 Typing

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    Enas A. S. Attia

    2010-01-01

    Full Text Available Background. Interleukin-4 (IL-4, a Th2 cytokine, can stimulate immunoglobulin E (IgE transcription. No previous studies evaluated the genetic mechanisms in nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL-4 and total IgE levels between Egyptian nonatopic AA patients and healthy subjects and to investigate a possible relation to HLA-DRB1 alleles. Results. Serum IL-4 and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients. Patients' HLA-DRB1 typing by sequence specific oligonucleotide probe technique was compared to normal Egyptian population. We found significantly elevated serum IL-4 and total IgE in AA patients (particularly alopecia universalis, AU, and chronic patients (P<.01. HLA-DRB1*11 is a general susceptibility/chronicity allele. DRB1*13 is a protective allele. DRB1*01 and DRB1*07 are linked to chronicity. Localized AA showed decreased DRB1*03 and DRB1*07. Extensive forms showed increased DRB1*08 and decreased DRB1*04. Elevated IL4 and IgE were observed in patients with DRB1*07 and DRB1*11 not DRB1*04. Conclusion. Serum IL-4 and IgE are elevated in nonatopic AA patients, particularly AU and chronic disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may have a role in determining type, magnitude, and duration of immune response in AA favouring increased IL4 and IgE.

  12. Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA-DRB1 Typing

    OpenAIRE

    Attia, Enas A. S.; El Shennawy, Dina; Sefin, Ashraf

    2010-01-01

    Background. Interleukin-4 (IL-4), a Th2 cytokine, can stimulate immunoglobulin E (IgE) transcription. No previous studies evaluated the genetic mechanisms in nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL-4 and total IgE levels between Egyptian nonatopic AA patients and healthy subjects and to investigate a possible relation to HLA-DRB1 alleles. Results. Serum IL-4 and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients. Patients' HL...

  13. Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

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    Paradowska-Gorycka, A; Stypińska, B; Olesińska, M; Felis-Giemza, A; Mańczak, M; Czuszynska, Z; Zdrojewski, Z; Wojciechowicz, J; Jurkowska, M

    2016-01-01

    Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1.

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    Luo, Mengchuan; Liu, Xiaofang; Meng, Huanyu; Xu, Liqun; Li, Yi; Li, Zhibin; Liu, Chang; Luo, Yue-Bei; Hu, Bo; Xue, Yuanyuan; Liu, Yu; Luo, Zhaohui; Yang, Huan

    2017-10-01

    Abnormal CD4 + T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4 + T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4 + T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4 + T cell-mediated immune responses in MG. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Serum Interleukin-4 and Total Immunoglobulin E in Nonatopic Alopecia Areata Patients and HLA-DRB1 Typing.

    Science.gov (United States)

    Attia, Enas A S; El Shennawy, Dina; Sefin, Ashraf

    2010-01-01

    Background. Interleukin-4 (IL-4), a Th(2) cytokine, can stimulate immunoglobulin E (IgE) transcription. No previous studies evaluated the genetic mechanisms in nonatopic AA patients with elevated serum IgE. Objective. To compare serum IL-4 and total IgE levels between Egyptian nonatopic AA patients and healthy subjects and to investigate a possible relation to HLA-DRB1 alleles. Results. Serum IL-4 and total IgE were measured by ELISA in 40 controls and 54 nonatopic AA patients. Patients' HLA-DRB1 typing by sequence specific oligonucleotide probe technique was compared to normal Egyptian population. We found significantly elevated serum IL-4 and total IgE in AA patients (particularly alopecia universalis, AU, and chronic patients) (P Serum IL-4 and IgE are elevated in nonatopic AA patients, particularly AU and chronic disease. Relevant susceptibility, chronicity, and severity HLADRB1 alleles may have a role in determining type, magnitude, and duration of immune response in AA favouring increased IL4 and IgE.

  16. Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted α-Enolase T Cell Epitope in Rheumatoid Arthritis

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    Christina Gerstner

    2016-11-01

    Full Text Available Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA patients, are strongly associated to a specific set of HLA-DR alleles including HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody levels toward the dominant citrullinated B cell epitope from α-enolase are significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we identified α-enolase-derived T cell epitopes and demonstrated that native and citrullinated versions of several peptides bind with different affinities to HLA-DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified peptides are distributed throughout the entire length of the presented epitopes and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10, and p11. Importantly, in contrast to its native version peptide 26 (TSKGLFRAAVPSGAS, the HLA-DRB1*04:01-restricted citrullinated peptide Cit26 (TSKGLFCitAAVPSGAS elicited significant functional T cell responses in primary cells from RA patients. Comparative analysis of the crystal structures of HLA-DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the posttranslational modification did not alter the conformation of the peptide. And since citrullination is the only structural difference between the two complexes, this indicates that the neo-antigen Cit26 is recognized by T cells with high specificity to the citrulline residue.

  17. HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

    Science.gov (United States)

    Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

    2018-04-01

    HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

  18. HLA DRB1*03 as a possible common etiology of schizophrenia, Graves' disease, and type 2 diabetes.

    Science.gov (United States)

    Sayeh, Aicha; Ben Cheikh, Cheker; Mardessi, Ali; Mrad, Meriem; Nsiri, Brahim; Oumaya, Abdelaziz; Fekih-Mrissa, Najiba

    2017-01-01

    Autoimmune diseases and schizophrenia share many common features. Association studies confirm a shared genetic association in the human leukocyte antigen (HLA) region between schizophrenia and most autoimmune diseases. To our knowledge, the simultaneous syndromes of Graves' disease (GD) and type 2 diabetes (T2D) in schizophrenia are rare in Tunisia. We report a case of a 42-year-old woman admitted to the department of psychiatry for an acute relapse of chronic schizophrenia. Her medical history revealed that she was followed for Graves' disease and for a type 2 diabetes mellitus. A low-resolution HLA typing was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) techniques according to determine the patient's haplotype. Our study suggests that the HLA DRB1*03 allele may explain a common etiology underlying the co-morbidity of Graves' disease, type 2 diabetes, and schizophrenia in our patient.

  19. Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

    Science.gov (United States)

    Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

    2017-09-01

    Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

    Science.gov (United States)

    Spraggs, C F; Parham, L R; Briley, L P; Warren, L; Williams, L S; Fraser, D J; Jiang, Z; Aziz, Z; Ahmed, S; Demetriou, G; Mehta, A; Jackson, N; Byrne, J; Andersson, M; Toi, M; Harris, L; Gralow, J; Zujewski, J A; Crescenzo, R; Armour, A; Perez, E; Piccart, M

    2017-08-08

    HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10 -26 , n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.The Pharmacogenomics Journal advance online publication, 8 August 2017; doi:10.1038/tpj.2017.39.

  1. The Adaptive Change of HLA-DRB1 Allele Frequencies Caused by Natural Selection in a Mongolian Population That Migrated to the South of China.

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    Hao Sun

    Full Text Available Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another five ethnic groups. Meanwhile, 10 autosomal short tandem repeats (STRs were genotyped to assess the influence of genetic background on HLA-DRB1 frequencies. The frequencies of certain alleles changed significantly in the Mongolian population that migrated to Yunnan. For example, DRB1*12:02:01 increased from 6.1% to 35.4%. STR analysis excluded the possibility of a recent bottleneck and indicated that 50% of the genetic consistency between northern and southern Mongolians; Tajima's D value for HLA-DRB1 exon2 and dN/dS analysis showed that the HLA-DRB1 genes in both Mongolian populations were under balancing selection. However, the sites under natural selection changed. We proposed that the dramatically change of HLA frequencies in southern Mongolian was caused by a combination of inter-population gene flow and natural selection. Certain diseases specific to the south of China, such as malaria, may be the driving force behind the enhanced DRB1*12:02:01 frequency.

  2. [Relationship between HLA-DRB1 genotypes and efficacy of oral type II collagen treatment using chicken cartilage soup in rheumatoid arthritis].

    Science.gov (United States)

    Toda, Y; Takemura, S; Morimoto, T; Ogawa, R

    1997-02-01

    The correlation between the efficacy of type II collagen (C II) treatment of the rheumatoid arthritis (RA) and the existence of HLA-DRB 1 * 0405 allele was investigated in two groups of patients; the first group had HLA-DRB 1 * 0405 allele (the 0405 group) and the second had no such allele (the non-0405 group). Thirty-eight RA patients were given a chicken cartilage soup containing heat degenerated C II (the CII group) or a placebo soup (the placebo group) for three months. The 38 cases were composed of 11 cases in the 0405/C II group, 9 in the 0405/placebo group, 11 in the non-0405/C II group, 9 cases in the non-0405/placebo group. In the C II group, there was a significant increase in the anti-human C II IgA antibody serum titers (p = 0.003) and significant decrease in the anti-human C II IgG titer (p II and 0405/placebo groups (p of the swollen joints = 0.03, and p of the tender joints = 0.03), and between the 0405/C II and non-0405/C II groups (p = 0.006 and 0.01, respectively). We concluded that oral C II could have a therapeutic efficacy in RA patients with HLA-DRB 1 * 0405 allele.

  3. RhD Specific Antibodies Are Not Detectable in HLA-DRB11501* Mice Challenged with Human RhD Positive Erythrocytes

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    Lidice Bernardo

    2014-01-01

    Full Text Available The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB11501* to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB11501* as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW, CD1(ICR, and NSA(CF-1. DRB11501* mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB11501* mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB11501* mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB11501* transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed.

  4. Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis.

    Science.gov (United States)

    Disanto, Giulio; Hall, Carolina; Lucas, Robyn; Ponsonby, Anne-Louise; Berlanga-Taylor, Antonio J; Giovannoni, Gavin; Ramagopalan, Sreeram V

    2013-09-01

    Gene-environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92-10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79-2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59-2.59; excess risk due to interaction=3.30, 95%CI=0.47-6.12; attributable proportion due to interaction=45%, 95% CI=22-68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene-environment interactions on both a multiplicative and additive scale.

  5. Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Miyamae, Takako; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Goto, Hiroaki; Morita, Satoshi; Mizuki, Nobuhisa; Kimura, Akinori; Yokota, Shumpei

    2011-03-01

    Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

  6. Opposing effects of the HLA-DRB1*0301-DQB1*0201 haplotype on the risk for multiple sclerosis in diverse Arab populations in Israel.

    Science.gov (United States)

    Benedek, G; Paperna, T; Avidan, N; Lejbkowicz, I; Oksenberg, J R; Wang, J; Brautbar, C; Israel, S; Miller, A

    2010-07-01

    Different multiple sclerosis (MS) prevalence rates were reported for Muslim and Christian Arabs in Israel. In this study, we evaluated whether associations of human leukocyte antigen (HLA) genes with MS may contribute to this prevalence difference. DNA samples from Israeli Arab MS patients (n=109) and controls (n=132) were typed for HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and -DQB1) genes. Global comparisons of HLA allele frequencies revealed significant differences between Christians and Muslims; therefore, case-control analyses were stratified by religious affiliation. Disease characteristics of Muslim and Christian Arab MS patients were similar to those reported for European populations. Opposing association signals with MS were observed for alleles composing the DRB1*0301-DQB1*0201 haplotype: positive association of the HLA-DRB1*0301 allele in Muslims (P(Bonferroni)=0.004, odds ratio (OR)=3.07), and negative association in Christian Arabs (P(Bonferroni)=0.01, OR=0.12), with similar results obtained for HLA-DQB1*0201. HLA-B*52 was negatively associated with MS only in Muslims (P(Bonferroni)=0.01, OR=0.03). The study presents for the first time a high-resolution HLA gene analysis in clinically well-characterized Arab populations with MS, and shows the population-specific contribution of the DRB1*0301-DQB1*0201 haplotype to disease susceptibility.

  7. A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population

    International Nuclear Information System (INIS)

    Chen, Dan; Hammer, Joanna; Lindquist, David; Idahl, Annika; Gyllensten, Ulf

    2014-01-01

    In a genome-wide association study, we have previously identified and performed the initial replication of three novel susceptibility loci for cervical cancer: rs9272143 upstream of HLA-DRB1, rs2516448 adjacent to MHC class I polypeptide-related sequence A gene (MICA), and rs3117027 at HLA-DPB2. The risk allele T of rs2516448 is in perfect linkage disequilibrium with a frameshift mutation (A5.1) in MICA exon 5, which results in a truncated protein. To validate these associations in an independent study and extend our prior work to MICA exon 5, we genotyped the single-nucleotide polymorphisms at rs9272143, rs2516448, rs3117027 and the MICA exon 5 microsatellite in a nested case–control study of 961 cervical cancer patients (827 carcinoma in situ and 134 invasive carcinoma) and 1725 controls from northern Sweden. The C allele of rs9272143 conferred protection against cervical cancer (odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.65–0.82; P = 1.6 × 10 −7 ), which is associated with higher expression level of HLA-DRB1, whereas the T allele of rs2516448 increased the susceptibility to cervical cancer (OR = 1.33, 95% CI = 1.19–1.49; P = 5.8 × 10 −7 ), with the same association shown with MICA-A5.1. The direction and the magnitude of these associations were consistent with our previous findings. We also identified protective effects of the MICA-A4 (OR = 0.80, 95% CI = 0.68–0.94; P = 6.7 × 10 −3 ) and MICA-A5 (OR = 0.60, 95% CI = 0.50–0.72; P = 3.0 × 10 −8 ) alleles. The associations with these variants are unlikely to be driven by the nearby human leukocyte antigen (HLA) alleles. No association was observed between rs3117027 and risk of cervical cancer. Our results support the role of HLA-DRB1 and MICA in the pathogenesis of cervical cancer

  8. Association study between HLA-DRB, HLA-DQA1, HLA-DQB1 and breast cancer in Iranian women

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    Amirzargar AA

    2010-11-01

    -DQA1*0301 (p=0.001 and HLA-DRB1*1303 (p=0.02 and a lower frequency of HLA-DQA1*0101 (p=0.002 compared to healthy control."n"nConclusion: These findings provide information of a positive and negative association between certain alleles of HLA class II and breast cancer in our population and also might support that the pattern of inheritance in the early and late onset of breast cancer differ substantially.

  9. Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

    Science.gov (United States)

    Patente, Thiago A; Monteiro, Maria B; Vieira, Suzana M; Rossi da Silva, Maria E; Nery, Márcia; Queiroz, Márcia; Azevedo, Mirela J; Canani, Luis H; Parisi, Maria C; Pavin, Elizabeth J; Mainardi, Débora; Javor, Juraj; Velho, Gilberto; Coimbra, Cássio N; Corrêa-Giannella, Maria Lúcia

    2015-08-15

    A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes

    DEFF Research Database (Denmark)

    Spraggs, C F; Parham, L R; Briley, L P

    2018-01-01

    HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatm.......The Pharmacogenomics Journal advance online publication, 8 August 2017; doi:10.1038/tpj.2017.39....

  11. Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes

    DEFF Research Database (Denmark)

    Spraggs, C F; Parham, L R; Briley, L P

    2017-01-01

    HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatm.......The Pharmacogenomics Journal advance online publication, 8 August 2017; doi:10.1038/tpj.2017.39....

  12. Influence and interactions of cathepsin D, HLA-DRB1 and APOE on cognitive abilities in an older non-demented population.

    Science.gov (United States)

    Payton, A; van den Boogerd, E; Davidson, Y; Gibbons, L; Ollier, W; Rabbitt, P; Worthington, J; Horan, M; Pendleton, N

    2006-01-01

    Cathepsin D (CTSD), human leukocyte antigen DRB1 (HLA-DRB1) and apolipoprotein E (APOE) have all been associated with cognitive ability in both demented and non-demented individuals. CTSD is a pleiotrophic protein whose functions include the processing of proteins prior to presentation by HLA. Several studies have also reported that a functional exon 2 polymorphism in the CTSD gene interacts with APOEepsilon4 resulting in an increased risk of developing Alzheimer's disease (AD). We have previously reported that the CTSD exon 2 polymorphism regulates fluid intelligence. In this study, we extend this finding to other cognitive domains and investigate interactions with APOE and HLA-DRB1. Using a cohort of 766 non-demented volunteers, we found that the CTSD exon 2 T allele was associated with a decrease in several cognitive domains that comprise processing speed [random letters (RLs) test, P = 0.012; alphabet-coding task (ACT), P = 0.001], spatial recall (SR) (P = 0.016) and an additional test of fluid intelligence (P = 0.010). We also observed that the HLA-DR1 was associated with enhanced cumulative recall ability (P = 0.006), and conversely HLA-DR5 was associated with diminished delayed verbal recall and SR abilities (P = 0.014 and P = 0.003, respectively). When analysed independently, APOEepsilon4 did not influence any cognitive domains. In contrast, CTSD T/APOEepsilon4-positive volunteers scored lower on tests of fluid intelligence (P = 0.015), processing speed (ACT, P = 0.001; RL, P = 0.013) and immediate recall (P = 0.029). Scores were lower for all these tests than when CTSD and APOE were analysed independently. This supports previous findings in AD that have also reported an epistatic interaction. In addition, we found that CTSD T/HLA-DR2-positive volunteers had reduced processing speed (ACT, P = 0.040; RL, P = 0.014) and had significantly lower cumulative and SR abilities (P = 0.003 and P = 0.001, respectively). Biological interaction between these two

  13. Associação do HLA-DRB5*01 com proteção contra manifestação cutânea da vasculite reumatoide em pacientes brasileiros Association of HLA-DRB5*01 with protection against cutaneous manifestations of rheumatoid vasculitis in Brazilian patients

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    Wester Eidi Nishimura

    2012-06-01

    Full Text Available OBJETIVO: Avaliar a frequência do HLA classes I e II e sua associação com a manifestação cutânea da vasculite reumatoide (VR em pacientes brasileiros. PACIENTES E MÉTODOS: Durante um ano foram selecionados 130 pacientes com artrite reumatoide (AR, classificados de acordo com os critérios do American College of Rheumatology de 1987. Os pacientes foram submetidos a um questionário clínico e laboratorial para exclusão de outras causas de vasculopatia cutânea (neoplasia, infecções, uso de drogas ilícitas, diabetes mellitus e tabagismo. Setenta e três foram excluídos por apresentarem algum fator de risco para outras causas de vasculopatias. Cinquenta e sete foram incluídos no estudo sem fator de risco para outras causas de vasculopatia, dos quais 17 apresentavam VR de acordo com os critérios de 1984 de Scott e Bacon. Foram analisados dados demográficos, tempo de diagnóstico de AR, atividade da doença (DAS28 e presença de fator reumatoide e de anticorpos antipeptídeo citrulinado cíclico. Alelos HLA foram tipificados usando-se a reação em cadeia da polimerase-DNA amplificada por hibridização de baixa resolução com sequências específicas de sondas. RESULTADOS: A comparação entre os 40 pacientes sem VR e os 17 pacientes com VR demonstrou uma frequência aumentada do HLA-B*14 (Pc = 0,168 e do HLA-Cw*08 (Pc = 0,084 em pacientes com VR, e uma frequência aumentada do HLA-DRB5*01 (Pc = 0,048 em pacientes sem VR. CONCLUSÃO: O HLA-DRB5*01 pode conferir proteção contra essa manifestação extra-articular da AR.OBJECTIVE: To evaluate the frequency of HLA classes I and II and their association with the cutaneous manifestation of rheumatoid vasculitis (RV in Brazilian patients. PATIENTS AND METHODS: During one year we selected 130 patients with rheumatoid arthritis (RA classified according to the American College of Rheumatology, 1987. All patients underwent a clinical and laboratory questionnaire to exclude other causes of

  14. Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood

    International Nuclear Information System (INIS)

    Ovsyannikova, Inna G.; Johnson, Kenneth L.; Naylor, Stephen; Muddiman, David C.; Poland, Gregory A.

    2003-01-01

    This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines

  15. Polimorfismo de los alelos de los antígenos de leucocitos humanos HLA-DRB1 y su asociación con la artritis reumatoidea juvenil en una muestra de niños mestizos colombianos.

    Directory of Open Access Journals (Sweden)

    Gloria Garavito

    2003-09-01

    Full Text Available Se buscó tipificar molecularmente los alelos de los antígenos de leucocitos humanos HLADRB1 en un grupo de niños mestizos colombianos (población resultante de la mezcla genética de amrindios, europeos y africanos con artritis reumatoidea juvenil (ARJ, así como analizar su frecuencia de expresión y compararla con sujetos clínicamente normales e investigar la asociación entre la frecuencia de los alelos con los diferentes subgrupos clínicos de ARJ. El estudio involucró 65 pacientes con ARJ y 65 controles sanos. La tipificación de los alelos HLADRB1 se realizó por medio de la metodología de la reacción en cadena de la polimerasa con sondas de oligonucleótidos de secuencias específicas (PCR-SSOP, utilizando el protocolo recomendado por el XII International Histocompatibilty Workshop, realizado en St. Malo, París, en 1996. Los alelos HLADRB1* 1104 (prueba exacta de Fisher, PEF=0,013, OR=16,79, frecuencia etiológica (FE=0,93 y DRB1*1602 (PEF=0,016, OR=8,98, FE=0,88 se evidenciaron como marcadores de susceptibilidad. HLA-DRB1*1501 (FP=0,466; p=0,005 y HLA DRB1*1402 (FP=0,49; p=0,009 se comportaron como alelos asociados con protección. Al comparar las asociaciones entre alelos y los diferentes subgrupos clínicos se encontró asociación entre ARJ oligoarticular con HLA-DRB1* 1104 (p=0,0034, OR=41,53 , FE=0,97, la ARJ poliarticular se asoció con el alelo HLADRB1* 0404 (p=0,012, OR=8,75, FE=0,88 y en el grupo sistémico, el alelo más expresado fue el HLA-DRB1*1602 (p=0,005, OR=21,33, FE=0,95. La presencia de factor reumatoide estuvo asociado con los alelos HLA-DRB1*0407 (p=0,05, OR=11,2, FE=0,45 y HLA-DRB1*1302 (p=0,02, OR=22,8, FE=0,63. En el grupo de pacientes con ANA+, sólo hubo significancia estadística para el alelo HLA-DRB1* 0701 (p=0,001, OR=58, FE=0,73. Nuestros resultados sugieren que los genes del MHC en este subgrupo étnico inciden no sólo en la susceptibilidad a desarrollar ARJ sino también en la expresión cl

  16. Evaluation of LABType® SSO HLA Typing using the Luminex Platform: Cord Blood Registry Typing for the Korean Population.

    Science.gov (United States)

    Roh, Eun-Youn; Song, Eun-Young; Chang, Jee-Young; Yoon, Jong-Hyun; Shin, Sue

    2016-08-01

    The performance of a new intermediate-resolution method using a PCR-Luminex platform and LABType® SSO A, B DRB1 kits as an HLA typing method for the cord blood (CB) registry of the Korean population was investigated. A total of 1,413 cord blood units (CBUs) were enrolled - 1,382 from Koreans and 31 from non-Koreans or mixed-ancestry individuals. HLA-A, -B, and -DRB1 typing was performed using the LABType® SSO typing kits. HLA typing with the DNA method and 2-digit results are mandatory for the public CB bank in Korea according to the "CB Act." The proportions of ambiguous results in the 2-digit assignment were 14.6% (206/1,413) and 14.8% (205/ 1,382) among the total subjects and the Korean donors, respectively. In the 2-digit resolution, 3 different HLA-A types (69 CBUs), 31 HLA-B types (124 CBUs), and 3 HLA-DRB1 types (13 CBUs) showed ambiguous results. The 'most probable type' to the ambiguous results based on the reported Korean HLA allele frequencies were able to be assigned. The most probable results were 100% consistent with the confirmed types as determined by the HD kits (DRB1) and additional PCR-SBT or PCR-SSP tests (A and B). Luminex technology is more automated and less labor intensive than the conventional SSO typing method, and the results are less affected by differences between inspectors. Although it is not satisfactory as a sole confirmation test and cannot be used as a replacement for the PCR-SBT test, the combination of Luminex technology with LABType® SSO kits and population frequency data provides a proper typing platform that can be used as a qualifying test for CB registries.

  17. Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.

    Directory of Open Access Journals (Sweden)

    Antonio Alcina

    Full Text Available The human leukocyte antigen (HLA DRB1*1501 has been consistently associated with multiple sclerosis (MS in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS. We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.

  18. Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations

    Science.gov (United States)

    Abad-Grau, María del Mar; Fedetz, María; Izquierdo, Guillermo; Lucas, Miguel; Fernández, Óscar; Ndagire, Dorothy; Catalá-Rabasa, Antonio; Ruiz, Agustín; Gayán, Javier; Delgado, Concepción; Arnal, Carmen

    2012-01-01

    The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone. PMID:22253788

  19. Common and Low Frequency Variants in MERTK Are Independently Associated with Multiple Sclerosis Susceptibility with Discordant Association Dependent upon HLA-DRB1*15:01 Status.

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    Michele D Binder

    2016-03-01

    Full Text Available Multiple Sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients.

  20. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

    DEFF Research Database (Denmark)

    Goyette, Philippe; Boucher, Gabrielle; Mallon, Dermot

    2015-01-01

    high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA......Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including...

  1. Population data on D6S2879 and D6S2806 markers located at HLA-DRB1 region in the Iranians: Identifying the signatures of balancing and directional selection

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    Mansoureh Tajadod

    2011-12-01

    Full Text Available In this study, the genetic diversity and neutrality test for the MHC microsatellite loci, D6S2879 and D6S2806, located within the HLA-DRB1 gene region, were investigated. The genotyping data from 73 unrelated individuals were analyzed for Shannon index, the effective allele number of the markers and neutrality test by use of PyPop and Popgene32 programs. The Shannon index for D6S2879 and D6S2806 markers in the studied population was 1.0372 and 0.8601, respectively. The Fnd value computed for D6S2879 and D6S2806 markers were also estimated -0.8449 and 0.9904, respectively. The results obtained from Ewens-Watterson test indicated that D6S2879 and D6S2806 markers were under balancing and directional selection in the Iranian populations, respectively. The data suggested the presence of a selection force on HLA-DRB1 gene region in the Iranian populations.

  2. HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.

    Science.gov (United States)

    Chen, Zhiyong; Wang, Yan; Kuwana, Masataka; Xu, Xue; Hu, Wei; Feng, Xuebing; Wang, Hong; Kimura, Akinori; Sun, Lingyun

    2017-09-01

    Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (p c ) = 3.8 × 10 -8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, p c = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10 -6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10 -4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD. DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.

  3. Genetic variations in STAT4,C2,HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis.

    Science.gov (United States)

    Jiang, De-Ke; Ma, Xiao-Pin; Wu, Xiaopan; Peng, Lijun; Yin, Jianhua; Dan, Yunjie; Huang, Hui-Xing; Ding, Dong-Lin; Zhang, Lu-Yao; Shi, Zhuqing; Zhang, Pengyin; Yu, Hongjie; Sun, Jielin; Lilly Zheng, S; Deng, Guohong; Xu, Jianfeng; Liu, Ying; Guo, Jinsheng; Cao, Guangwen; Yu, Long

    2015-11-05

    Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P = 1.79 × 10(-2), OR = 1.17, 95% CI = 1.03-1.34; rs9267673: P = 4.91 × 10(-4), OR = 1.37, 95% CI = 1.15-1.63; rs2647073: P = 3.53 × 10(-5), OR = 1.63, 95% CI = 1.29-2.06; rs3997872: P = 4.22 × 10(-4), OR = 1.86, 95% CI = 1.32-2.62; rs9275319: P = 1.30 × 10(-2), OR = 1.32, 95% CI = 1.06-1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.

  4. HLA DRB1*, DQB1*, DPA1* y DPB1* y su asociación con la patogénesis de las leucemias en población venezolana

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    Sergio E. Rivera-Pirela

    2016-08-01

    Full Text Available Background: The HLA complex is involved in the pathogenesis of leukemia. Objectives: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL and 48 with chronic myeloid leukemia (CML for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. Methods: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. Results: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3; alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1. Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 were negatively associated. Conclusions: The absence of associations with HLA-DRB1 * region in ALL and other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML.

  5. HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 Haplotype Protects Autoantibody-Positive Relatives From Type 1 Diabetes Throughout the Stages of Disease Progression.

    Science.gov (United States)

    Pugliese, Alberto; Boulware, David; Yu, Liping; Babu, Sunanda; Steck, Andrea K; Becker, Dorothy; Rodriguez, Henry; DiMeglio, Linda; Evans-Molina, Carmella; Harrison, Leonard C; Schatz, Desmond; Palmer, Jerry P; Greenbaum, Carla; Eisenbarth, George S; Sosenko, Jay M

    2016-04-01

    The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype. A comparison with 60 autoantibody-negative relatives suggested protection from autoantibody development. Moreover, the relatives with DRB1*15:01-DQA1*01:02-DQB1*06:02 less frequently expressed autoantibodies associated with higher T1D risk, were less likely to have multiple autoantibodies at baseline, and rarely converted from single to multiple autoantibody positivity on follow-up. These relatives also had lower frequencies of metabolic abnormalities at baseline and exhibited no overall metabolic worsening on follow-up. Ultimately, they had a very low 5-year cumulative incidence of T1D. In conclusion, the protective influence of DRB1*15:01-DQA1*01:02-DQB1*06:02 spans from autoantibody development through all stages of progression, and relatives with this allele only rarely develop T1D. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. A new classification of HLA-DRB1 alleles based on acid-base properties of the amino acids located at positions 13, 70 and 71: impact on ACPA status or structural progression, and meta-analysis on 1235 patients with rheumatoid from two cohorts (ESPOIR and EAC cohort).

    Science.gov (United States)

    Ruyssen-Witrand, Adeline; van Steenbergen, Hanna W; van Heemst, Jurgen; Gourraud, Pierre-Antoine; Nigon, Delphine; Lukas, Cédric; Miceli-Richard, Corinne; Jamard, Bénédicte; Cambon-Thomsen, Anne; Cantagrel, Alain; Dieudé, Philippe; van der Helm-van Mil, Annette H M; Constantin, Arnaud

    2015-01-01

    To group HLA-DRB1 alleles based on acid-base properties of amino acids at positions 13, 70 and 71 and analyse their association with the presence of anticitrullinated peptide antibodies (ACPA) and structural progression in 2 cohorts of early rheumatoid arthritis (RA). Patients with RA (N=612) from ESPOIR cohort and from EAC cohort (n=624) were genotyped for HLA-DRB1 alleles. The alleles containing the RAA sequence at positions 72-74 were classified into 3 groups according to the amino acid at positions 13, 70 and 71: BB encoding basic amino acids at positions 13, 70 and 71; A encoding acidic amino acids at positions 70 and 71; and BN encoding either neutral amino acids at position 13 and basic amino acids at positions 70 and 71, or basic amino acid at position 13 and neutral amino acids at positions 70 and 71. The associations between the different alleles and (1) the ACPA presence, and (2) the structural progression were assessed by χ(2) test; a meta-analysis was performed on the 2 cohorts using the Mantel-Haenszel method. After meta-analysis, BB alleles were significantly associated with ACPA presence (OR (95% CI) 4.08 (3.14 to 5.31)) and structural progression (OR (95% CI) 2.33 (1.76 to 3.09)). The alleles protected significantly against ACPA presence (OR (95% CI) 0.37 (0.28 to 0.50)) and structural progression (OR (95% CI) 0.34 (0.23 to 0.50)). This acid-base classification allowed to separate another group BN with an intermediate risk of ACPA production (OR (95% CI) 1.14 (0.91 to 1.44)) and structural progression (OR (95% CI) 1.01 (0.77 to 1.33)). This new classification permitted to make a hierarchy of HLA-DRB1 alleles in terms of association with ACPA presence or structural progression in early RA.

  7. User behavior in Smart and Sustainable Offices (SSO

    Directory of Open Access Journals (Sweden)

    M. W. Kozusznik

    2018-01-01

    Full Text Available Smart and Sustainable Offices (SSO require synergies between technologies and users behaviors. The sociotechnical approach considers users’ motives, attitudes, cognitions and behaviors when designing work environments. This note will describe those phenomena in office environments. It will also present a set of tools to assess those phenomena and will provide guidelines to improve them.

  8. Frequency of alleles and haplotypes of the human leukocyte antigen system in Bauru, São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Luana de Cassia Salvadori

    2014-04-01

    Full Text Available Background: HLA allele identification is used in bone marrow transplant programs as HLA compatibility between the donor and recipient may prevent graft rejection. Objective: This study aimed to estimate the frequency of alleles and haplotypes of the HLA system in the region of Bauru and compare these with the frequencies found in other regions of the country. Methods: HLA-A*, HLA-B*, and HLA-DRB1* allele frequencies and haplotypes were analyzed in a sample of 3542 volunteer donors at the National Registry of Voluntary Bone Marrow Donors (REDOME in Bauru. HLA low resolution typing was performed using reverse line blot with the Dynal Reli(tm SSO-HLA Typing Kit and automated Dynal AutoReli(tm48 device (Invitrogen, USA. Results: Twenty, 36, and 13 HLA-A*, HLA-B*, and HLA-DRB1* allele groups, respectively, were identified. The most common alleles for each locus were HLA-A*02, HLA-B*35, and HLA-DRB1*07. The most frequent haplotype was A*01-B*08-DRB1*03. Allele and haplotype frequencies were compared to other regions in Brazil and the similarities and differences among populations are shown. Conclusion: The knowledge of the immunogenic profile of a population contributes to the comprehension of the historical and anthropological aspects of different regions. Moreover, this helps to find suitable donors quickly, thereby shortening waiting lists for transplants and thus increasing survival rates among recipients.

  9. The Sso7d protein of Sulfolobus solfataricus: in vitro relationship among different activities

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    Annamaria Guagliardi

    2002-01-01

    Full Text Available The physiological role of the nonspecific DNA-binding protein Sso7d from the crenarchaeon Sulfolobus solfataricus is unknown. In vitro studies have shown that Sso7d promotes annealing of complementary DNA strands (Guagliardi et al. 1997, induces negative supercoiling (Lopez-Garcia et al. 1998, and chaperones the disassembly and renaturation of protein aggregates in an ATP hydrolysis-dependent manner (Guagliardi et al. 2000. In this study, we examined the relationships among the binding of Sso7d to double-stranded DNA, its interaction with protein aggregates, and its ATPase activity. Experiments with 1-anilinonaphthalene-8-sulfonic acid as probe demonstrated that exposed hydrophobic surfaces in Sso7d are responsible for interactions with protein aggregates and double-stranded DNA, whereas the site of ATPase activity has a non-hydrophobic character. The interactions of Sso7d with double-stranded DNA and with protein aggregates are mutually exclusive events, suggesting that the disassembly activity and the DNA-related activities of Sso7d may be competitive in vivo. In contrast, the hydrolysis of ATP by Sso7d is independent of the binding of Sso7d to double-stranded DNA or protein aggregates.

  10. Smart and Sustainable Offices (SSO: Showcasing a holistic approach to realise the next generation offices

    Directory of Open Access Journals (Sweden)

    A. Cobaleda Cordero

    2018-01-01

    Full Text Available The Smart Sustainable Offices project (SSO is a product of years of research with large sets of data collected from more than 30 office buildings in Switzerland, Sweden, and Spain. Based on scientific evidence, the concept of SSO, initially conceived as a research plan to address the interdependencies between office users and their working environment in a European context, is now used as a qualitative and quantitative mixed method approach for office diagnosis and ideation. At the current stage, the SSO methodology aims to implement a new paradigm of user-oriented, lower carbon footprint and resilient office design solutions. The main strategy is articulated around the “office DNA” of every organisation, decoded as a compound of work patterns, operational and individual needs, and their potential to define design criteria. The practical application of SSO and its tentative findings exemplified through three pilot test office-demonstrators are described in this paper.

  11. Relying on the Information

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    TK YAYIN KURULU

    2013-11-01

    Full Text Available The editorial discusses internet filtering in the light of the optional internet packages for users, namely Family, Standard, Kids and Domestic, to be offered by the Information Technologies Board with the "Secure Internet Law" to take effect on August 22, 2011. Also sharing the hesitations about the objectivity of the application with the reader, editorial emphasizes an education system focused on breeding citizens who are not scared of relying on the information and who can, by themselves, decide whether information is harmful or not. References are made to the results of similar applications abroad while the press statement made by Turkish NGOs on the issue are included.

  12. Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA--positive rheumatoid arthritis in three Asian ethnic groups.

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    Too Chun-Lai

    Full Text Available BACKGROUND: To investigate the associations between HLA-DRB1 shared epitope (SE alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. METHODS: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. RESULTS: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. CONCLUSION: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

  13. UTILIZATION OF MOODLE WEB SERVICE BASED SYSTEM TO SYSTEM WITH SIAKAD AND SSO UNS

    Directory of Open Access Journals (Sweden)

    Ristu Saptono

    2017-01-01

    Full Text Available The development of information technology in education allows for integration between systems so every system can be optimized. Elearning, SIAKAD, and SSO UNS are education system in UNS (Universitas Sebelas Maret but they are not integrated yet. Course data for elearning is still manual and SSO which can not be used to log into SIAKAD. In this study the integration of elearning, SIAKAD, and SSO utilizing REST web service and exchange data using JSON. As a result, the integration of additional system must use a bridge application as a customizer data between elearning and SIAKAD. While the results of the testing to include one course, 40 lecturers, and 40 students, including automatically enroll is 60.22 seconds, while the time required for unenroll lecturers and students is 2:13 seconds. To enroll course, lecturers and students when there are previously data was 28.5 seconds.

  14. Peningkatan Sistem Keamanan Autentikasi Single Sign On (SSO Menggunakan Algoritma AES dan One-Time Password Studi Kasus: SSO Universitas Ubudiyah Indonesia

    Directory of Open Access Journals (Sweden)

    Zuhar Musliyana

    2016-03-01

    Full Text Available Single Sign On (SSO merupakan model autentikasi independen yang diimplementasikan Universitas Ubudiyah Indonesia (UUI menggunakan Message-Digest Algorithm 5 (MD5 dan web service NuSOAP berbasis bahasa pemograman PHP. Sistem ini berjalan pada protokol Hypertext Transfer Protocol (HTTP. Faktanya penggunaan protokol HTTP ini sangat rentan terhadap berbagai jenis serangan karena data dikirim dalam bentuk plaintext tanpa ada proses enkripsi dan penerapan algoritma MD5 pada autentikasi login juga rentan terhadap serangan dictionary attacks dan rainbow tables. Disisi lain, Penggunaan web service NuSOAP juga menciptakan celah keamanan karena pengiriman dan penerimaan payload tidak dienkripsi. Saat ini diketahui sudah ada beberapa metode yang dapat digunakan untuk meningkatkan pengamanan kerentanan tersebut diantaranya yaitu menggunakan Hypertext Transfer Protocol Secure (HTTPS, Secure Hypertext Transfer Protocol (SHTTP dan Completely Automated Public Turing test to tell Computers and Humans Apart (CAPTCHA. Namun beberapa hasil penelitian terkait memperlihatkan masih terdapat beberapa kelemahan dari penggunaan HTTPS, SHTTP dan CAPTCHA. Penelitian ini mengusulkan penggunaan algoritma Advanced Encryption Standard (AES dengan pembangkit kunci dinamis dan metode One-Time Password (OTP berbasis sinkronisasi waktu dengan kombinasi salt untuk meningkatkan keamanan pada autentikasi SSO UUI. Hasil pengujian menunjukkan penerapan algoritma AES dan OTP  dapat mengamankan proses autentikasi SSO  dari serangan dictionary attack dan rainbow table.

  15. Differential active site loop conformations mediate promiscuous activities in the lactonase SsoPox.

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    Julien Hiblot

    Full Text Available Enzymes are proficient catalysts that enable fast rates of Michaelis-complex formation, the chemical step and products release. These different steps may require different conformational states of the active site that have distinct binding properties. Moreover, the conformational flexibility of the active site mediates alternative, promiscuous functions. Here we focused on the lactonase SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with promiscuous phosphotriesterase activity. We identified a position in the active site loop (W263 that governs its flexibility, and thereby affects the substrate specificity of the enzyme. We isolated two different sets of substitutions at position 263 that induce two distinct conformational sampling of the active loop and characterized the structural and kinetic effects of these substitutions. These sets of mutations selectively and distinctly mediate the improvement of the promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by increasing active-site loop flexibility. These observations corroborate the idea that conformational diversity governs enzymatic promiscuity and is a key feature of protein evolvability.

  16. Global identification of hnRNP A1 binding sites for SSO-based splicing modulation

    DEFF Research Database (Denmark)

    Bruun, Gitte H; Doktor, Thomas K; Borch-Jensen, Jonas

    2016-01-01

    for this deregulation by blocking other SREs with splice-switching oligonucleotides (SSOs). However, the location and sequence of most SREs are not well known. RESULTS: Here, we used individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) to establish an in vivo binding map for the key splicing...... regulatory factor hnRNP A1 and to generate an hnRNP A1 consensus binding motif. We find that hnRNP A1 binding in proximal introns may be important for repressing exons. We show that inclusion of the alternative cassette exon 3 in SKA2 can be significantly increased by SSO-based treatment which blocks an i...... downstream of the 5' splice site can be blocked by SSOs to activate the exon. CONCLUSIONS: The hnRNP A1 binding map can be used to identify potential targets for SSO-based therapy. Moreover, together with the hnRNP A1 consensus binding motif, the binding map may be used to predict whether disease...

  17. Re-excision rates after breast conserving surgery following the 2014 SSO-ASTRO guidelines.

    Science.gov (United States)

    Heelan Gladden, Alicia A; Sams, Sharon; Gleisner, Ana; Finlayson, Christina; Kounalakis, Nicole; Hosokawa, Patrick; Brown, Regina; Chong, Tae; Mathes, David; Murphy, Colleen

    2017-12-01

    In 2014, SSO-ASTRO published guidelines which recommended "no ink on tumor" as adequate margins for patients undergoing breast conservation for invasive breast cancer. In 2016, new SSO-ASTRO-ASCO guidelines recommended 2 mm margins for DCIS. We evaluated whether these guidelines affected re-excision rates at our institution. Patients treated with breast conservation surgery from January 1, 2010-March 1, 2016 were identified. Re-excision rates, tumor characteristics, and presence of residual disease were recorded. The 2016 guidelines were retrospectively applied to the same cohort and expected re-excision rates calculated. Re-excision rates did not significantly decline before and after 2014 guideline adoption (11.9% before, 10.9% after; p = 0.65) or when the 2016 guidelines were retrospectively applied (8.4%; p = 0.10). The 2014 and 2016 guidelines had minimal impact on our re-excision rates, as most re-excisions were done for DCIS and 2016 guidelines supported our prior institutional practices of 2 mm margins for these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly.

    Science.gov (United States)

    Munson, M; Chen, X; Cocina, A E; Schultz, S M; Hughson, F M

    2000-10-01

    In the eukaryotic secretory and endocytic pathways, transport vesicles shuttle cargo among intracellular organelles and to and from the plasma membrane. Cargo delivery entails fusion of the transport vesicle with its target, a process thought to be mediated by membrane bridging SNARE protein complexes. Temporal and spatial control of intracellular trafficking depends in part on regulating the assembly of these complexes. In vitro, SNARE assembly is inhibited by the closed conformation adopted by the syntaxin family of SNAREs. To visualize this closed conformation directly, the X-ray crystal structure of a yeast syntaxin, Sso1p, has been determined and refined to 2.1 A resolution. Mutants designed to destabilize the closed conformation exhibit accelerated rates of SNARE assembly. Our results provide insight into the mechanism of SNARE assembly and its intramolecular and intermolecular regulation.

  19. Distribution of HLA-DRB1/DQB1 alleles and DRB1-DQB1 ...

    African Journals Online (AJOL)

    Marwa Chaouali

    2017-03-17

    Mar 17, 2017 ... Background: Autoimmune hepatitis (AIH) is a chronic inflammatory disease characterized by necrotic inflammation leading to hepatocyte destruction. The association of human leukocyte antigens (HLA) with. AIH development and onset is not fully elucidated especially in the Tunisian population. Objectives: ...

  20. Structural and Dynamic Insight into Hirudin Epitopes-HLA- DRB1 ...

    African Journals Online (AJOL)

    It is produced in the salivary glands of the leech Hirudo .... for epitope selection has a specific algorithm and was developed in ..... from Plasmodium falciparum pre-erythrocytic-stage antigens ... Comar M. Identification of a vaccine against.

  1. Research on Shaft Subsynchronous Oscillation Characteristics of Parallel Generators and SSDC Application in Mitigating SSO of Multi-Generators

    Directory of Open Access Journals (Sweden)

    Shen Wang

    2015-02-01

    Full Text Available Subsynchronous oscillation (SSO of generators caused by high voltage direct current (HVDC systems can be solved by applying supplemental subsynchronous damping controller (SSDC. SSDC application in mitigating SSO of single-generator systems has been studied intensively. This paper focuses on SSDC application in mitigating SSO of multi-generator systems. The phase relationship of the speed signals of the generators under their common mechanical natural frequencies is a key consideration in SSDC design. The paper studies in detail the phase relationship of the speed signals of two generators in parallel under their shared mechanical natural frequency, revealing regardless of whether the two generators are identical or not, there always exists a common-mode and an anti-mode under their common natural frequency, and the phase relationship of the speed signals of the generators depends on the extent to which the anti-mode is stimulated. The paper further demonstrates that to guarantee the effectiveness of SSDC, the anti-phase mode component of its input signal should be eliminated. Based on the above analysis, the paper introduces the design process of SSDC for multi-generator systems and verifies its effectiveness through simulation in Power Systems Computer Aided Design/Electromagnetic Transients including Direct Current (PSCAD/EMTDC.

  2. JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

    DEFF Research Database (Denmark)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens

    2014-01-01

    sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast...

  3. Síndrome Poliglandular Autoinmune Tipo II: Posible Asociación con HLA DRB1*-DQB1* Possible association of Type II Autoimmune Polyendrocrine Syndrome with HLA DRB1*-DQB1*

    OpenAIRE

    M.S. Mallea Gil; M.C. Ballarino; M.M. Aparicio; K. Bertini; M.C. Ridruejo; S. Gimenez; P. Galarza; A. Perusco; S. Roveto; D. Rimoldi

    2010-01-01

    Los síndromes poliendocrinos autoinmunes (APS) asocian enfermedades endocrinas autoinmunes con otros desórdenes autoinmunes no endocrinos. El APS tipo II se caracteriza por compromiso primario suprarrenal, tiroideo y/o DM tipo I. Presentamos un paciente masculino de 46 años que fue internado por astenia, adinamia, hiporexia, severa disminución de peso, mareos y vómitos. Antecedente de obesidad y diabetes diagnosticada 3 años antes. Presentaba hipotensión arterial, hiperpigmentación de mucosas...

  4. The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.

    Science.gov (United States)

    Mikk, M-L; Kiviniemi, M; Laine, A-P; Härkönen, T; Veijola, R; Simell, O; Knip, M; Ilonen, J

    2014-01-01

    To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting. The HLA-B*39 allele significantly increased the disease risk conferred by DRB1*04:04-DQA1*03-DQB1*03:02 and (DR8)-DQB1*04 haplotypes. The same effect was observed on genotype level as disease association for the HLA-B*39 allele was observed in multiple genotypes containing DRB1*04:04-DQA1*03-DQB1*03:02 or (DR8)-DQB1*04 haplotypes. Finally we considered the two common subtypes of the HLA-B*39 allele, B*39:01 and B*39:06 and observed their unequal distribution when stratified for specific DR-DQ haplotypes. The risk for type 1 diabetes conferred by certain DR/DQ haplotypes is modified by the presence of the HLA-B*39 and this confirms the independent disease predisposing effect of the HLA-B*39 allele. The results can be applied in enhancing the sensitivity and specificity of DR/DQ based screening programs for subjects at disease risk. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  5. HLA-DRB1*16-restricted recognition of myeloid cells, including CD34+ CML progenitor cells

    NARCIS (Netherlands)

    Ebeling, Saskia B.; Ivanov, Roman; Hol, Samantha; Aarts, Tineke I.; Hagenbeek, Anton; Verdonck, Leo F.; Petersen, Eefke J.

    2003-01-01

    The therapeutic effect of a human leucocyte antigen (HLA)-identical allogeneic stem cell transplantation (allo-SCT) for the treatment of haematological malignancies is mediated partly by the allogeneic T cells that are administered together with the stem cell graft. Chronic myeloid leukaemia (CML)

  6. Juxtaposed Color Halftoning Relying on Discrete Lines

    OpenAIRE

    Babaei, Vahid; Hersch, Roger

    2013-01-01

    Most halftoning techniques allow screen dots to overlap. They rely on the assumption that the inks are transparent, i.e. the inks do not scatter a significant portion of the light back to the air. However, many special effect inks such as metallic inks, iridescent inks or pigmented inks are not transparent. In order to create halftone images, halftone dots formed by such inks should be juxtaposed, i.e. printed side by side. We propose an efficient juxtaposed color halftoning technique for pla...

  7. An atom trap relying on optical pumping

    International Nuclear Information System (INIS)

    Bouyer, P.; Lemonde, P.; Ben Dahan, M.; Michaud, A.; Salomon, C.; Dalibard, J.

    1994-01-01

    We have investigated a new radiation pressure trap which relies on optical pumping and does not require any magnetic field. It employs six circularly polarized divergent beams and works on the red of a J g →J e = J g + 1 atomic transition with J g ≥1/2. We have demonstrated this trap with cesium atoms from a vapour cell using the 852 nm J g = 4→J e = 5 resonance transition. The trap contained up to 3.10 7 atoms in a cloud of 1/√e radius of 330 μm. (orig.)

  8. Enabling Secure XMPP Communications in Federated IoT Clouds Through XEP 0027 and SAML/SASL SSO.

    Science.gov (United States)

    Celesti, Antonio; Fazio, Maria; Villari, Massimo

    2017-02-07

    Nowadays, in the panorama of Internet of Things (IoT), finding a right compromise between interactivity and security is not trivial at all. Currently, most of pervasive communication technologies are designed to work locally. As a consequence, the development of large-scale Internet services and applications is not so easy for IoT Cloud providers. The main issue is that both IoT architectures and services have started as simple but they are becoming more and more complex. Consequently, the web service technology is often inappropriate. Recently, many operators in both academia and industry fields are considering the possibility to adopt the eXtensible Messaging and Presence Protocol (XMPP) for the implementation of IoT Cloud communication systems. In fact, XMPP offers many advantages in term of real-time capabilities, efficient data distribution, service discovery and inter-domain communication compared to other technologies. Nevertheless, the protocol lacks of native security, data confidentiality and trustworthy federation features. In this paper, considering an XMPP-based IoT Cloud architectural model, we discuss how can be possible to enforce message signing/encryption and Single-Sign On (SSO) authentication respectively for secure inter-module and inter-domain communications in a federated environment. Experiments prove that security mechanisms introduce an acceptable overhead, considering the obvious advantages achieved in terms of data trustiness and privacy.

  9. Enabling Secure XMPP Communications in Federated IoT Clouds Through XEP 0027 and SAML/SASL SSO

    Directory of Open Access Journals (Sweden)

    Antonio Celesti

    2017-02-01

    Full Text Available Nowadays, in the panorama of Internet of Things (IoT, finding a right compromise between interactivity and security is not trivial at all. Currently, most of pervasive communication technologies are designed to work locally. As a consequence, the development of large-scale Internet services and applications is not so easy for IoT Cloud providers. The main issue is that both IoT architectures and services have started as simple but they are becoming more and more complex. Consequently, the web service technology is often inappropriate. Recently, many operators in both academia and industry fields are considering the possibility to adopt the eXtensible Messaging and Presence Protocol (XMPP for the implementation of IoT Cloud communication systems. In fact, XMPP offers many advantages in term of real-time capabilities, efficient data distribution, service discovery and inter-domain communication compared to other technologies. Nevertheless, the protocol lacks of native security, data confidentiality and trustworthy federation features. In this paper, considering an XMPP-based IoT Cloud architectural model, we discuss how can be possible to enforce message signing/encryption and Single-Sign On (SSO authentication respectively for secure inter-module and inter-domain communications in a federated environment. Experiments prove that security mechanisms introduce an acceptable overhead, considering the obvious advantages achieved in terms of data trustiness and privacy.

  10. Enabling Secure XMPP Communications in Federated IoT Clouds Through XEP 0027 and SAML/SASL SSO

    Science.gov (United States)

    Celesti, Antonio; Fazio, Maria; Villari, Massimo

    2017-01-01

    Nowadays, in the panorama of Internet of Things (IoT), finding a right compromise between interactivity and security is not trivial at all. Currently, most of pervasive communication technologies are designed to work locally. As a consequence, the development of large-scale Internet services and applications is not so easy for IoT Cloud providers. The main issue is that both IoT architectures and services have started as simple but they are becoming more and more complex. Consequently, the web service technology is often inappropriate. Recently, many operators in both academia and industry fields are considering the possibility to adopt the eXtensible Messaging and Presence Protocol (XMPP) for the implementation of IoT Cloud communication systems. In fact, XMPP offers many advantages in term of real-time capabilities, efficient data distribution, service discovery and inter-domain communication compared to other technologies. Nevertheless, the protocol lacks of native security, data confidentiality and trustworthy federation features. In this paper, considering an XMPP-based IoT Cloud architectural model, we discuss how can be possible to enforce message signing/encryption and Single-Sign On (SSO) authentication respectively for secure inter-module and inter-domain communications in a federated environment. Experiments prove that security mechanisms introduce an acceptable overhead, considering the obvious advantages achieved in terms of data trustiness and privacy. PMID:28178214

  11. Juxtaposed color halftoning relying on discrete lines.

    Science.gov (United States)

    Babaei, Vahid; Hersch, Roger D

    2013-02-01

    Most halftoning techniques allow screen dots to overlap. They rely on the assumption that the inks are transparent, i.e., the inks do not scatter a significant portion of the light back to the air. However, many special effect inks, such as metallic inks, iridescent inks, or pigmented inks, are not transparent. In order to create halftone images, halftone dots formed by such inks should be juxtaposed, i.e., printed side by side. We propose an efficient juxtaposed color halftoning technique for placing any desired number of colorant layers side by side without overlapping. The method uses a monochrome library of screen elements made of discrete lines with rational thicknesses. Discrete line juxtaposed color halftoning is performed efficiently by multiple accesses to the screen element library.

  12. Molecular typing of HLA class II antigens in a São Paulo population

    Directory of Open Access Journals (Sweden)

    Goldberg A.C.

    1998-01-01

    Full Text Available In the present paper we show data obtained from a normal population with a racially mixed profile typical of the city of São Paulo, State of São Paulo. Data were generated with polymerase chain reaction using sequence specific primers (PCR-SSP for HLA-DRB and polymerase chain reaction followed by hybridization with sequence specific oligonucleotide probes (PCR-SSO for HLA-DQA1 and HLA-DQB1 loci. HLA-DRB, DQA1, DQB1 and haplotype frequencies as well as common linkage disequilibria were found. This population was also shown to be in genetic equilibrium according to the Hardy-Weinberg law. HLA-DR typing of a normal sample from the city of Porto Velho, State of Rondonia, highlighted the importance of different sets of HLA profiles found in other regions of the country. This database provides essential information for screening studies of disease associations, forensic analyses and transplants.

  13. Immission-load-related dynamics of S-SO42− in precipitation and in lysimetric solutions penetrating through beech ecosystems

    Directory of Open Access Journals (Sweden)

    Kukla Ján

    2017-12-01

    Full Text Available The paper presents the results of a 23-year study of sulphate sulphur dynamics in beech ecosystems exposed to different immission loads. The amounts of S-SO42− in precipitation water entering the ecosystems were: the Kremnické vrchy Mts, a clear-cut area 519 kg ha−1 (24.7 kg ha−1 per year, a beech forest 476 kg ha−1 (22.7 kg ha−1 per year; the Štiavnické vrchy Mts an open place 401 kg ha−1 (24.6 kg ha−1 per year, a beech forest 324 kg ha−1 (19.1 kg ha−1 per year. The average SO42− concentrations in lysimetric solutions penetrating through surface humus to a depth of Cambisol 10 and 25 cm were increased as follows: in the Kremnické vrchy Mts from 12.71 to 16.17 mg l−1 and in the Štiavnické vrchy Mts from 18.73 to 28.80 mg l−1. The S-SO4−2 amounts penetrating the individual soil layers in the Kremnické vrchy Mts were as follows: in case of surface humus on clear-cut area 459 kg ha−1 (20.9 kg ha−1 per year, in beech forest 433 kg ha−1 (19.7 kg ha−1 per year; below 10 cm organo-mineral layer of the mentioned plots penetrated 169–171 kg ha−1 (7.7–7.8 kg ha−1 per year, and below 25 cm mineral layer 155–255 kg ha−1 (7.1−11.6 kg ha−1 per year – a higher amount was found on clear-cut area with an episodic lateral flow of soil solutions. In beech forest of the Štiavnické vrchy Mts penetrated below surface humus 424 kg ha−1 S-SO42− (18.9 kg ha−1 per year, below 10 cm mineral layer 458 kg ha−1 S-SO42− (19.9 kg ha−1 per year, and below 25 cm mineral layer as much as 599 kg ha−1 S-SO42− (26.0 kg ha−1 per year. This fact was caused by frequent lateral flow of soil solutions. The results indicate that the assumption about lower immission load of the beech ecosystem in the Kremnické vrchy Mts is wrong, at least in the case of S-SO42−. The testing has revealed that the studied beech ecosystems differ very significantly in sulphur amounts penetrating under 0.10 m and 0.25 m. The

  14. Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas

    Science.gov (United States)

    Fueling Stations Colorado Airport Relies on Natural Gas Fueling Stations to someone by E-mail Share Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas Fueling Stations on Facebook Tweet about Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas Fueling Stations on

  15. Tumour necrosis factor-α polymorphism as one of the complex inherited factors in pemphigus

    Directory of Open Access Journals (Sweden)

    Jolanta Dorota Torzecka

    2003-01-01

    Full Text Available The aim of our study was to analyse a significance of tumour necrosis factor (TNF-α promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-α gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls.

  16. Reliģijas makdonaldizācija

    OpenAIRE

    Siliņš, Toms

    2012-01-01

    Bakalaura darbā apskatītas makdonaldizācijas procesa izpausmes Latvijas reliģisko organizāciju darbībā. Pētījuma mērķis ir noskaidrot makdonaldizācijas izpausmes Latvijas reliģiskajās organizācijās, tādēļ izvirzīti pētījuma jautājumi – kādas ir liecības par makdonaldizācijas procesa ietekmi uz reliģiskajām organizācijām Latvijā un kā vērtējama makdonaldizācijas procesa ietekme uz reliģiskajām organizācijām Latvijā. Pētījuma ietvaros veiktas divas ekspertu intervijas, kuru analīzes rezultātā i...

  17. The structure of SSO2064, the first representative of Pfam family PF01796, reveals a novel two-domain zinc-ribbon OB-fold architecture with a potential acyl-CoA-binding role

    International Nuclear Information System (INIS)

    Krishna, S. Sri; Aravind, L.; Bakolitsa, Constantina; Caruthers, Jonathan; Carlton, Dennis; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Reyes, Ron; Rife, Christopher L.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of SSO2064, the first structural representative of Pfam family PF01796 (DUF35), reveals a two-domain architecture comprising an N-terminal zinc-ribbon domain and a C-terminal OB-fold domain. Analysis of the domain architecture, operon organization and bacterial orthologs combined with the structural features of SSO2064 suggests a role involving acyl-CoA binding for this family of proteins. SSO2064 is the first structural representative of PF01796 (DUF35), a large prokaryotic family with a wide phylogenetic distribution. The structure reveals a novel two-domain architecture comprising an N-terminal, rubredoxin-like, zinc ribbon and a C-terminal, oligonucleotide/oligosaccharide-binding (OB) fold domain. Additional N-terminal helical segments may be involved in protein–protein interactions. Domain architectures, genomic context analysis and functional evidence from certain bacterial representatives of this family suggest that these proteins form a novel fatty-acid-binding component that is involved in the biosynthesis of lipids and polyketide antibiotics and that they possibly function as acyl-CoA-binding proteins. This structure has led to a re-evaluation of the DUF35 family, which has now been split into two entries in the latest Pfam release (v.24.0)

  18. Intuitive Face Judgments Rely on Holistic Eye Movement Pattern

    Directory of Open Access Journals (Sweden)

    Laura F. Mega

    2017-06-01

    Full Text Available Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an ‘intuitive group,’ instructed to rely on their “gut feeling” for the authenticity judgments, and a ‘deliberative group,’ instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the “gestalt” of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research.

  19. Intuitive Face Judgments Rely on Holistic Eye Movement Pattern.

    Science.gov (United States)

    Mega, Laura F; Volz, Kirsten G

    2017-01-01

    Non-verbal signals such as facial expressions are of paramount importance for social encounters. Their perception predominantly occurs without conscious awareness and is effortlessly integrated into social interactions. In other words, face perception is intuitive. Contrary to classical intuition tasks, this work investigates intuitive processes in the realm of every-day type social judgments. Two differently instructed groups of participants judged the authenticity of emotional facial expressions, while their eye movements were recorded: an 'intuitive group,' instructed to rely on their "gut feeling" for the authenticity judgments, and a 'deliberative group,' instructed to make their judgments after careful analysis of the face. Pixel-wise statistical maps of the resulting eye movements revealed a differential viewing pattern, wherein the intuitive judgments relied on fewer, longer and more centrally located fixations. These markers have been associated with a global/holistic viewing strategy. The holistic pattern of intuitive face judgments is in line with evidence showing that intuition is related to processing the "gestalt" of an object, rather than focusing on details. Our work thereby provides further evidence that intuitive processes are characterized by holistic perception, in an understudied and real world domain of intuition research.

  20. Maladies reliées aux loisirs aquatiques

    Science.gov (United States)

    Sanborn, Margaret; Takaro, Tim

    2013-01-01

    Résumé Objectif Passer en revue les facteurs de risque, la prise en charge et la prévention des maladies reliées aux loisirs aquatiques en pratique familiale. Sources des données Des articles originaux et de synthèse entre janvier 1998 et février 2012 ont été identifiés à l’aide de PubMed et des expressions de recherche en anglais water-related illness, recreational water illness et swimmer illness. Message principal Il y a un risque de 3 % à 8 % de maladies gastrointestinales (MGI) après la baignade. Les groupes à risque élevé de MGI sont les enfants de moins de 5 ans, surtout s’ils n’ont pas été vaccinés contre le rotavirus, les personnes âgées et les patients immunodéficients. Les enfants sont à plus grand risque parce qu’ils avalent plus d’eau quand ils nagent, restent dans l’eau plus longtemps et jouent dans l’eau peu profonde et le sable qui sont plus contaminés. Les adeptes des sports dans lesquels le contact avec l’eau est abondant comme le triathlon et le surf cerf-volant sont aussi à risque élevé et même ceux qui s’adonnent à des activités impliquant un contact partiel avec l’eau comme la navigation de plaisance et la pêche ont un risque de 40 % à 50 % fois plus grand de MGI par rapport à ceux qui ne pratiquent pas de sports aquatiques. Il y a lieu de faire une culture des selles quand on soupçonne une maladie reliée aux loisirs aquatiques et l’échelle clinique de la déshydratation est utile pour l’évaluation des besoins de traitement chez les enfants affectés. Conclusion Les maladies reliées aux loisirs aquatiques est la principale cause de MGI durant la saison des baignades. La reconnaissance que la baignade est une source importante de maladies peut aider à prévenir les cas récurrents et secondaires. On recommande fortement le vaccin contre le rotavirus chez les enfants qui se baignent souvent.

  1. Robust Sensing of Approaching Vehicles Relying on Acoustic Cues

    Directory of Open Access Journals (Sweden)

    Mitsunori Mizumachi

    2014-05-01

    Full Text Available The latest developments in automobile design have allowed them to be equipped with various sensing devices. Multiple sensors such as cameras and radar systems can be simultaneously used for active safety systems in order to overcome blind spots of individual sensors. This paper proposes a novel sensing technique for catching up and tracking an approaching vehicle relying on an acoustic cue. First, it is necessary to extract a robust spatial feature from noisy acoustical observations. In this paper, the spatio-temporal gradient method is employed for the feature extraction. Then, the spatial feature is filtered out through sequential state estimation. A particle filter is employed to cope with a highly non-linear problem. Feasibility of the proposed method has been confirmed with real acoustical observations, which are obtained by microphones outside a cruising vehicle.

  2. Luminex® xMAP® technology is an effective strategy for high-definition human leukocyte antigen typing of cord blood units prior to listing.

    Science.gov (United States)

    Guarene, Marco; Badulli, Carla; Cremaschi, Anna L; Sbarsi, Ilaria; Cacciatore, Rosalia; Tinelli, Carmine; Pasi, Annamaria; Bergamaschi, Paola; Perotti, Cesare G

    2018-05-01

    Allele-level donor-recipient match at HLA-A, HLA-B, HLA-C and HLA-DRB1 loci impacts the outcome after cord blood transplantation for hematologic malignancies and modifies the strategy of donor selection. High definition of both class I and II HLA loci at time of listing is a way to improve the attractiveness of cord blood bank inventories, reducing the time for donor search and procurement and simplifying donor choice, in particular, for patients of non-European heritage. In 2014, Luminex ® xMAP ® technology was introduced in our laboratory practice and was applied to cord blood units typing. In this study, we evaluated the impact of this strategy in comparison with the platform in use until 2013, relying on LiPA reverse polymerase chain reaction-sequence-specific oligonucleotide (revPCR-SSO) plus polymerase chain reaction-sequence-specific primer (PCR-SSP). In 2014, the time for testing was shorter (141 vs 181 days on average), the number of test repetitions was lower (in particular for HLA-A locus, p = 0.026), and the cost reduced (240.7 vs 395.6 euros per unit on average) compared to 2013, demonstrating that Luminex xMAP technology is superior to the previous approach. Luminex xMAP platform has useful application in cord blood banking programs, to achieve high-definition HLA typing of cord blood units at the time of banking in a quick, accurate, and cost-effective manner.

  3. da Vinci decoded: does da Vinci stereopsis rely on disparity?

    Science.gov (United States)

    Tsirlin, Inna; Wilcox, Laurie M; Allison, Robert S

    2012-11-01

    In conventional stereopsis, the depth between two objects is computed based on the retinal disparity in the position of matching points in the two eyes. When an object is occluded by another object in the scene, so that it is visible only in one eye, its retinal disparity cannot be computed. Nakayama and Shimojo (1990) found that a precept of quantitative depth between the two objects could still be established for such stimuli and proposed that this precept is based on the constraints imposed by occlusion geometry. They named this and other occlusion-based depth phenomena "da Vinci stereopsis." Subsequent research found quantitative depth based on occlusion geometry in several other classes of stimuli grouped under the term da Vinci stereopsis. However, Nakayama and Shimojo's findings were later brought into question by Gillam, Cook, and Blackburn (2003), who suggested that quantitative depth in their stimuli was perceived based on conventional disparity. In order to understand whether da Vinci stereopsis relies on one type of mechanism or whether its function is stimulus dependent we examine the nature and source of depth in the class of stimuli used by Nakayama and Shimojo (1990). We use three different psychophysical and computational methods to show that the most likely source for depth in these stimuli is occlusion geometry. Based on these experiments and previous data we discuss the potential mechanisms responsible for processing depth from monocular features in da Vinci stereopsis.

  4. Human children rely more on social information than chimpanzees do.

    Science.gov (United States)

    van Leeuwen, Edwin J C; Call, Josep; Haun, Daniel B M

    2014-11-01

    Human societies are characterized by more cultural diversity than chimpanzee communities. However, it is currently unclear what mechanism might be driving this difference. Because reliance on social information is a pivotal characteristic of culture, we investigated individual and social information reliance in children and chimpanzees. We repeatedly presented subjects with a reward-retrieval task on which they had collected conflicting individual and social information of equal accuracy in counterbalanced order. While both species relied mostly on their individual information, children but not chimpanzees searched for the reward at the socially demonstrated location more than at a random location. Moreover, only children used social information adaptively when individual knowledge on the location of the reward had not yet been obtained. Social information usage determines information transmission and in conjunction with mechanisms that create cultural variants, such as innovation, it facilitates diversity. Our results may help explain why humans are more culturally diversified than chimpanzees. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  5. [Scope of the latest RE-LY substudies: clinical implications].

    Science.gov (United States)

    Ruiz-Giménez Arrieta, N

    2012-03-01

    The approval of the use of dabiatran in stroke prevention in patients with nonvalvular atrial fibrilation (NVAF) is based on the results of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, one of the largest studies to date in this entity. In this trial, dabigatran showed similar safety and efficacy to warfarin in primary and secondary prevention of stroke in patients with AF. At a dose of 150 mg twice daily, dabigatran was superior to warfarin in the prevention of stroke or systemic embolism and the 110 mg dose twice daily showed similar efficacy and greater safety, given the lower incidence of hemorrhage. These results were consistently found in the various subanalyses, with some slight differences of interest for clinical practice. The ideal candidates for dabiatran are patients with NVAF suitable for cardioversion, who require short periods of anticoagulation, patients in remote geographical areas with difficulty in achieving good anticoagulation control or good control with anti-vitamin K treatment due to IRN fluctuations, and patients with a low risk of hemorrhage and a CHADS score ≥ 3 and/or with prior stroke, whenever there are no contraindications. The choice of dabigatran dose should be evaluated according to the patient's individual characteristics (caution must be exercised when prescribing this drug in the elderly and in renal insufficiency) and embolic and/or hemorrhagic risk. Studies of the long-term safety of this drug, pharmacoeconomic analyses in Spain and post-commercialization pharmacovigilance data are required before the definitive uses of this drug can be established. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  6. Identification of anthropogenic and natural inputs of sulfate into a karstic coastal groundwater system in northeast China: evidence from major ions, δ13CDIC and δ34SSO4

    Science.gov (United States)

    Han, Dongmei; Song, Xianfang; Currell, Matthew J.

    2016-05-01

    The hydrogeochemical processes controlling groundwater evolution in the Daweijia area of Dalian, northeast China, were characterised using hydrochemistry and isotopes of carbon and sulfur (δ13CDIC and δ34SSO4). The aim was to distinguish anthropogenic impacts as distinct from natural processes, with a particular focus on sulfate, which is found at elevated levels (range: 54.4 to 368.8 mg L-1; mean: 174.4 mg L-1) in fresh and brackish groundwater. The current investigation reveals minor seawater intrusion impact (not exceeding 5 % of the overall solute load), in contrast with extensive impacts observed in 1982 during the height of intensive abstraction. This indicates that measures to restrict groundwater abstraction have been effective. However, hydrochemical facies analysis shows that the groundwater remains in a state of ongoing hydrochemical evolution (towards Ca-Cl type water) and quality degradation (increasing nitrate and sulfate concentrations). The wide range of NO3 concentrations (74.7-579 mg L-1) in the Quaternary aquifer indicates considerable input of fertilisers and/or leakage from septic systems. Both δ13C (-14.5 to -5.9 permil) and δ34SSO4 (+5.4 to +13.1 permil) values in groundwater show increasing trends along groundwater flow paths. While carbonate minerals may contribute to increasing δ13CDIC and δ34SSO4 values in deep karstic groundwater, high loads of agricultural fertilisers reaching the aquifer via irrigation return flow are likely the main source of the dissolved sulfate in Quaternary groundwater, as shown by distinctive isotopic ratios and a lack of evidence for other sources in the major ion chemistry. According to isotope mass balance calculations, the fertiliser contribution to overall sulfate has reached an average of 62.1 % in the Quaternary aquifer, which has a strong hydraulic connection to the underlying carbonate aquifer. The results point to an alarming level of impact from the local intensive agriculture on the groundwater

  7. Genetic factors and multiple sclerosis in the Moroccan population: a role for HLA class II.

    Science.gov (United States)

    Ouadghiri, S; El Alaoui Toussi, K; Brick, C; Ait Benhaddou, E H; Benseffaj, N; Benomar, A; El Yahyaoui, M; Essakalli, M

    2013-12-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease. Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS. A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR=2.67, 95% CI=1.36-5.23, P=0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR=2.78, 95% CI=1.41-5.48, P=0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found. Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Evaluation of Ion Torrent sequencing technology for rapid clinical human leucocyte antigen typing.

    Science.gov (United States)

    Guerra, Sandra G; Chong, Winnie; Brown, Colin J; Navarrete, Cristina V

    2018-06-05

    The development of techniques to define the human leucocyte antigen (HLA) region has proven to be challenging due to its high level of polymorphism. Within a clinical laboratory, a technique for high-resolution HLA typing, which is rapid and cost effective is essential. NGS has provided a rapid, high-resolution HLA typing solution, which has reduced the number of HLA ambiguities seen with other typing methods. In this study, the One Lambda NXType NGS kit was tested on the Ion Torrent PGM platform. A total of 362 registry donors from four ethnic populations (Europeans, South Asians, Africans and Chinese) were NGS HLA typed across 9-loci (HLA-A, -B, -C, -DRB1,-DRB345 -DQB1 and -DPB1). Concordance rates of 91%-98% were obtained (for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) when compared to historical PCR-SSO HLA types, and the identification of uncommon alleles such as A*24:07:01 and C*04:82 were observed. A turnaround time of four days was achieved for typing 44 samples. However, some limitations were observed; primer locations did not allow all ambiguities to be resolved for HLA Class II where Exon I and IV amplification are needed (HLA-DRB1*04:07:01/04:92, HLA-DRB1*09:01:02/*09:21 and HLA-DRB1*12:01:01/*12:10). This study has demonstrated high-resolution typing by NGS can be achieved in an acceptable turnaround time for a clinical laboratory; however, the Ion Torrent workflow has some technical limitations that should be addressed. © 2018 John Wiley & Sons Ltd.

  9. Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and

    Science.gov (United States)

    Natural Gas Vehicles St. Louis Airport Relies on Biodiesel and Natural Gas Vehicles to someone by E-mail Share Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and Natural Gas Vehicles on Facebook Tweet about Alternative Fuels Data Center: St. Louis Airport Relies on Biodiesel and

  10. Distribution of HLA-A, -B and -DRB1 genes and haplotypes in the Tujia population living in the Wufeng Region of Hubei Province, China.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available BACKGROUND: The distribution of HLA alleles and haplotypes varies widely between different ethnic populations and geographic areas. Before any genetic marker can be used in a disease-associated study it is therefore essential to investigate allelic frequencies and establish a genetic database. METHODOLOGY/PRINCIPAL FINDINGS: This is the first report of HLA typing in the Tujia group using the Luminex HLA-SSO method HLA-A, -B and -DRB1 allelic distributions were determined in 124 unrelated healthy Tujia individuals, and haplotypic frequencies and linkage disequilibrium parameters were estimated using the maximum-likelihood method. In total 10 alleles were detected at the HLA-A locus, 21 alleles at the HLA-B locus and 14 alleles at the HLA-DRB1 locus. The most frequently observed alleles in the HLA-I group were HLA-A*02 (35.48%, A*11 (28.23%, A*24 (15.73%; HLA-B*40 (25.00%, B*46 (16.13%, and B*15 (15.73%. Among HLA-DRB1 alleles, high frequencies of HLA-DRB1*09 (25.81% were observed, followed by HLA-DRB1*15 (12.9%, and DRB1*12 (10.89%. The two-locus haplotypes at the highest frequency were A*02-B*46A (8.47%, followed by A*11-B*40 (7.66%, A*02-B*40 (8.87%, A*11-B*15 (6.45%, A*02-B*15 (6.05%, B*40-DRB1*09 (9.27% and B*46-DRB1*09 (6.45%. The most common three-locus haplotypes found in the Tujia population were A*02-B*46-DRB1*09 (4.84% and A*02-B*40-DRB1*09 (4.03%. Fourteen two-loci haplotypes had significant linkage disequilibrium. Construction of a neighbor-joining phylogenetic tree and principal component analysis using the allelic frequencies at HLA-A was performed to compare the Tujia group and twelve other previously reported populations. The Tujia population in the Wufeng of Hubei Province had the closest genetic relationship with the central Han population, and then to the Shui, the Miao, the southern Han and the northern Han ethnic groups. CONCLUSIONS/SIGNIFICANCE: These results will become a valuable source of data for tracing population

  11. Human leukocyte antigen class I, class II, and tumor necrosis factor-alpha polymorphisms in a healthy elder Mexican Mestizo population

    Directory of Open Access Journals (Sweden)

    Llorente Luis

    2005-11-01

    Full Text Available Abstract Background There is strong evidence that an individual's genetic background is an important predisposing factor to longevity. In the present study we analysed the frequency of HLA class I, class II, as well as the TNF-α -308 polymorphism that may be related to an increased life span in Mexican Mestizo healthy elders. Results HLA typing was performed by polymerase chain reaction sequence specific oligonucleotide (PCR SSO reverse dot blot. The TNF-α -308 polymorphism was assessed by PCR restriction fragment length polymorphism. A significant increased frequency of HLA-DRB1*11 was found in elderly women whereas this allele was not present in elderly males. The TNF2 allele was also increased in the elder group when compared to young controls. The frequencies of the remaining alleles tested were not statistically different among groups. Conclusion These data suggest an ethnicity independent tendency of HLA-DRB1*11 in elder females to increase life span and a possible role of the TNF2 allele with the successful remodelling of senescent immune system.

  12. Association between HLA genes and dust mite sensitivity in a Brazilian population.

    Science.gov (United States)

    da Costa Lima Caniatti, Marcela Caleffi; Borelli, Sueli Donizete; Guilherme, Ana Lúcia Falavigna; Tsuneto, Luiza Tamie

    2017-02-01

    Type I hypersensitivity, also known as IgE-mediated allergy, is a complex, multifactorial condition whose onset and severity are influenced by both genetic and environmental factors. Mite allergens stimulate the production of humoral response (IgE), especially in children, which is closely involved in atopic asthma and rhinitis. This study aimed to investigate the association between HLA class I (-A, -B, and -C), and HLA class II (-DRB1) genes in individuals sensitive to dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus, or Blomia tropicalis) and mite-insensitive controls. 396 participants were grouped as mite-sensitive and mite-insensitive according to immediate hypersensitivity as determined by skin-prick tests, and to HLA genotyping by polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO). After chi-square heterogeneity testing no significant differences were observed in HLA-A, B, and C genes, except for the HLA-DRB1 locus, which, showed a negative association for DRB1∗04, between mite-sensitive and mite-insensitive individuals. In high resolution, DRB1∗04:11 allele was significantly different from all other results (P=0.0042, OR=0.26, and 95%CI=0.09-0.70). The analysis stratified by etiologic agent confirmed these associations. Our results suggest a possible association between HLA-DRB1 genes and hypersensitivity to dust mites. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  13. 47 CFR 15.717 - TVBDs that rely on spectrum sensing.

    Science.gov (United States)

    2010-10-01

    ... Television Band Devices § 15.717 TVBDs that rely on spectrum sensing. (a) Parties may submit applications for... that are identical in electrical characteristics and antenna systems may be certified under the...

  14. Increasing Uncertainty: The Dangers of Relying on Conventional Forces for Nuclear Deterrence

    Science.gov (United States)

    2016-03-14

    72 | Air & Space Power Journal Increasing Uncertainty The Dangers of Relying on Conventional Forces for Nuclear Deterrence Jennifer Bradley To put...relationships and should serve as the cornerstone of US nuclear deterrence policy. Although Russia and China are not identified as adversaries of...exactly what has happened over the past year. The US decision to meet the needs of deterrence by relying less on nuclear weapons and instead devel- oping

  15. Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia

    OpenAIRE

    Libia M. Rodríguez; Mabel C. Giraldo; Natalia García; Laura Velásquez; Sara C. París; Cristiam M. Álvarez; Luis F. García

    2007-01-01

    Introducción. La caracterización genética del sistema HLA es de gran utilidad en estudios antropogenéticos, en la comprensión de mecanismos asociados a susceptibilidad o resistencia a diversas enfermedades, en los fenómenos inmunológicos durante el embarazo y en la selección de donantes/receptores en trasplantes de órganos. Objetivo. Determinar las frecuencias alélicas, genotípicas y haplotípicas HLA-A, -B, -DRB1 en donantes fallecidos en Medellín. Materiales y métodos. Se incluyeron 92...

  16. Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia

    Directory of Open Access Journals (Sweden)

    Libia M. Rodríguez

    2007-12-01

    Conclusiones. Estos resultados corroboran la composición triétnica de nuestra población, en la cual predomina el grado de mezcla caucásica, a diferencia de otras latinoamericanas, y podrán ser usados como referencia para otros estudios y aplicaciones en esta población.

  17. Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia

    OpenAIRE

    Rodríguez, Libia M; Giraldo, Mabel C; García, Natalia; Velásquez, Laura; París, Sara C; Álvarez, Cristiam M; García, Luis F

    2007-01-01

    Introducción. La caracterización genética del sistema HLA es de gran utilidad en estudios antropogenéticos, en la comprensión de mecanismos asociados a susceptibilidad o resistencia a diversas enfermedades, en los fenómenos inmunológicos durante el embarazo y en la selección de donantes/receptores en trasplantes de órganos. Objetivo. Determinar las frecuencias alélicas, genotípicas y haplotípicas HLA-A, -B, -DRB1 en donantes fallecidos en Medellín. Materiales y métodos. Se incluyeron 926 dona...

  18. Association of Human Leukocyte Antigen DRB1*15 and DRB1*15:01 Polymorphisms with Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta-Analysis

    Science.gov (United States)

    Liu, Shan; Li, Qing; Zhang, Ying; Li, Qiushuang; Ye, Baodong; Wu, Dijiong; Wu, Li; Lu, Hanti; Ji, Conghua

    2016-01-01

    This study aimed to review and quantitatively analyze (1) the association of aplastic anemia (AA) with human leukocyte antigen (HLA)-DRB1*15 and HLA-DRB1*15:01 polymorphisms and (2) the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to immunosuppressive therapy (IST) in AA. Published studies have reported conflicting and heterogeneous results regarding the association of HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms with response to IST in AA. The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical Literature, Wangfang and Chinese Social Sciences Citation Index databases were searched. All relevant publications were searched through December 2015. Odds ratio (OR), risk ratio (RR), and 95% confidence intervals (CI) for the comparison between case–control or cohort studies were evaluated. Finally, 24 articles were identified. For HLA-DRB1*15 and HLA-DRB1*15:01, the OR (95% CI) was 2.24(1.33–3.77), P 0.05). Sensitivity analyses revealed that the results were statistically robust. The meta-analysis suggested that HLA-DRB1*15 and HLA-DRB1*15:01 polymorphisms might be associated with increased AA risk in Asians. IST might be more effective in HLA-DRB1*15+ and HLA-DRB1*15:01+ Asian patients with AA than in HLA-DRB1*15− and HLA-DRB1*15:01− Asian patients with AA. Future studies with adequate methodological quality on gene–gene and gene–environment interactions and gene treatment may yield valid results. PMID:27611583

  19. 76 FR 69545 - Conditions and Requirements for Relying on Component Part Testing or Certification, or Another...

    Science.gov (United States)

    2011-11-08

    ... the final rule to incorporate the concept that a finished product certifier may rely upon finished... revised, on our own initiative, the final rule to incorporate the concept that a finished product... Vol. 76 Tuesday, No. 216 November 8, 2011 Part IV Consumer Product Safety Commission 16 CFR Parts...

  20. Cortical control of object-specific grasp relies on adjustments of both activity and effective connectivity

    DEFF Research Database (Denmark)

    Tia, Banty; Takemi, Mitsuaki; Kosugi, Akito

    2017-01-01

    The cortical mechanisms of grasping have been extensively studied in macaques and humans. Here, we investigated whether common marmosets could rely on similar mechanisms despite striking differences in manual dexterity. Two common marmosets were trained to grasp-and-pull three objects eliciting d...

  1. 77 FR 70117 - Purchase of Certain Debt Securities by Business and Industrial Development Companies Relying on...

    Science.gov (United States)

    2012-11-23

    ... 3235-AL02 Purchase of Certain Debt Securities by Business and Industrial Development Companies Relying... securities; (B) is engaged or proposes to engage in the business of issuing face-amount certificates of the... business of issuing redeemable securities, the operations of which are subject to regulation by the State...

  2. Un premier service mobile en Égypte qui relie les petits exploitants ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Un premier service mobile en Égypte qui relie les petits exploitants aux acheteurs. Un homme qui parle sur un téléphone mobile. Les petits exploitants agricoles dominent l'agriculture égyptienne, mais leur manque de connaissances en matière de commercialisation et de compétences techniques, ainsi qu'une mauvaise ...

  3. Logical Characterisation of Concept Transformations from Human into Machine relying on Predicate Logic

    DEFF Research Database (Denmark)

    Badie, Farshad

    2016-01-01

    Providing more human-like concept learning in machines has always been one of the most significant goals of machine learning paradigms and of human-machine interaction techniques. This article attempts to provide a logical specification of conceptual mappings from humans’ minds into machines......’ knowledge bases. I will focus on the representation of the mappings (transformations) relying on First-Order Predicate Logic. Additionally, the structure of concepts in the common ground between humans and machines will be analysed. It seems quite necessary to pay attention to the philosophy...

  4. Regulated Medicare Advantage And Marketplace Individual Health Insurance Markets Rely On Insurer Competition.

    Science.gov (United States)

    Frank, Richard G; McGuire, Thomas G

    2017-09-01

    Two important individual health insurance markets-Medicare Advantage and the Marketplaces-are tightly regulated but rely on competition among insurers to supply and price health insurance products. Many local health insurance markets have little competition, which increases prices to consumers. Furthermore, both markets are highly subsidized in ways that can exacerbate the impact of market power-that is, the ability to set price above cost-on health insurance prices. Policy makers need to foster robust competition in both sectors and avoid designing subsidies that make the market-power problem worse. Project HOPE—The People-to-People Health Foundation, Inc.

  5. Anemonefishes rely on visual and chemical cues to correctly identify conspecifics

    Science.gov (United States)

    Johnston, Nicole K.; Dixson, Danielle L.

    2017-09-01

    Organisms rely on sensory cues to interpret their environment and make important life-history decisions. Accurate recognition is of particular importance in diverse reef environments. Most evidence on the use of sensory cues focuses on those used in predator avoidance or habitat recognition, with little information on their role in conspecific recognition. Yet conspecific recognition is essential for life-history decisions including settlement, mate choice, and dominance interactions. Using a sensory manipulated tank and a two-chamber choice flume, anemonefish conspecific response was measured in the presence and absence of chemical and/or visual cues. Experiments were then repeated in the presence or absence of two heterospecific species to evaluate whether a heterospecific fish altered the conspecific response. Anemonefishes responded to both the visual and chemical cues of conspecifics, but relied on the combination of the two cues to recognize conspecifics inside the sensory manipulated tank. These results contrast previous studies focusing on predator detection where anemonefishes were found to compensate for the loss of one sensory cue (chemical) by utilizing a second cue (visual). This lack of sensory compensation may impact the ability of anemonefishes to acclimate to changing reef environments in the future.

  6. Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

    Science.gov (United States)

    McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

    2005-01-01

    Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands. PMID:17148346

  7. Episodic Memory Retrieval Functionally Relies on Very Rapid Reactivation of Sensory Information.

    Science.gov (United States)

    Waldhauser, Gerd T; Braun, Verena; Hanslmayr, Simon

    2016-01-06

    Episodic memory retrieval is assumed to rely on the rapid reactivation of sensory information that was present during encoding, a process termed "ecphory." We investigated the functional relevance of this scarcely understood process in two experiments in human participants. We presented stimuli to the left or right of fixation at encoding, followed by an episodic memory test with centrally presented retrieval cues. This allowed us to track the reactivation of lateralized sensory memory traces during retrieval. Successful episodic retrieval led to a very early (∼100-200 ms) reactivation of lateralized alpha/beta (10-25 Hz) electroencephalographic (EEG) power decreases in the visual cortex contralateral to the visual field at encoding. Applying rhythmic transcranial magnetic stimulation to interfere with early retrieval processing in the visual cortex led to decreased episodic memory performance specifically for items encoded in the visual field contralateral to the site of stimulation. These results demonstrate, for the first time, that episodic memory functionally relies on very rapid reactivation of sensory information. Remembering personal experiences requires a "mental time travel" to revisit sensory information perceived in the past. This process is typically described as a controlled, relatively slow process. However, by using electroencephalography to measure neural activity with a high time resolution, we show that such episodic retrieval entails a very rapid reactivation of sensory brain areas. Using transcranial magnetic stimulation to alter brain function during retrieval revealed that this early sensory reactivation is causally relevant for conscious remembering. These results give first neural evidence for a functional, preconscious component of episodic remembering. This provides new insight into the nature of human memory and may help in the understanding of psychiatric conditions that involve the automatic intrusion of unwanted memories. Copyright

  8. Cochlear implant users rely on tempo rather than on pitch information during perception of musical emotion.

    Science.gov (United States)

    Caldwell, Meredith; Rankin, Summer K; Jiradejvong, Patpong; Carver, Courtney; Limb, Charles J

    2015-09-01

    The purpose of this study was to investigate the extent to which cochlear implant (CI) users rely on tempo and mode in perception of musical emotion when compared with normal hearing (NH) individuals. A test battery of novel four-bar melodies was created and adapted to four permutations with alterations of tonality (major vs. minor) and tempo (presto vs. largo), resulting in non-ambiguous (major key/fast tempo and minor key/slow tempo) and ambiguous (major key/slow tempo, and minor key/fast tempo) musical stimuli. Both CI and NH participants listened to each clip and provided emotional ratings on a Likert scale of +5 (happy) to -5 (sad). A three-way ANOVA demonstrated an overall effect for tempo in both groups, and an overall effect for mode in the NH group. The CI group rated stimuli of the same tempo similarly, regardless of changes in mode, whereas the NH group did not. A subgroup analysis indicated the same effects in both musician and non-musician CI users and NH listeners. The results suggest that the CI group relied more heavily on tempo than mode in making musical emotion decisions. The subgroup analysis further suggests that level of musical training did not significantly impact this finding. CI users weigh temporal cues more heavily than pitch cues in inferring musical emotion. These findings highlight the significant disadvantage of CI users in comparison with NH listeners for music perception, particularly during recognition of musical emotion, a critically important feature of music.

  9. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

    Directory of Open Access Journals (Sweden)

    Amalia Lamana

    Full Text Available BACKGROUND: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS: We studied 640 patients with early arthritis (76% women; median age, 52 years, recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28 as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044. Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162. After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

  10. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

    Science.gov (United States)

    Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F; Lopez-Nevot, Miguel A; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

    2012-01-01

    The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

  11. Defining the buffering process by a triprotic acid without relying on Stewart-electroneutrality considerations.

    Science.gov (United States)

    Nguyen, Minhtri K; Kao, Liyo; Kurtz, Ira

    2011-08-17

    Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation). However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1) partitioning of H+ buffering; 2) conservation of mass; and 3) acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values were in excellent agreement

  12. Defining the buffering process by a triprotic acid without relying on stewart-electroneutrality considerations

    Directory of Open Access Journals (Sweden)

    Kao Liyo

    2011-08-01

    Full Text Available Abstract Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation. However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1 partitioning of H+ buffering; 2 conservation of mass; and 3 acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values

  13. Defining the buffering process by a triprotic acid without relying on stewart-electroneutrality considerations

    Science.gov (United States)

    2011-01-01

    Upon the addition of protons to an aqueous solution, a component of the H+ load will be bound i.e. buffered. In an aqueous solution containing a triprotic acid, H+ can be bound to three different states of the acid as well as to OH- ions that are derived from the auto-ionization of H2O. In quantifying the buffering process of a triprotic acid, one must define the partitioning of H+ among the three states of the acid and also the OH- ions in solution in order to predict the equilibrium pH value. However, previous quantitative approaches that model triprotic acid titration behaviour and used to predict the equilibrium pH rely on the mathematical convenience of electroneutrality/charge balance considerations. This fact has caused confusion in the literature, and has led to the assumption that charge balance/electroneutrality is a causal factor in modulating proton buffering (Stewart formulation). However, as we have previously shown, although charge balance can be used mathematically as a convenient tool in deriving various formulae, electroneutrality per se is not a fundamental physicochemical parameter that is mechanistically involved in the underlying buffering and proton transfer reactions. The lack of distinction between a mathematical tool, and a fundamental physicochemical parameter is in part a reason for the current debate regarding the Stewart formulation of acid-base analysis. We therefore posed the following question: Is it possible to generate an equation that defines and predicts the buffering of a triprotic acid that is based only on H+ partitioning without incorporating electroneutrality in the derivation? Towards this goal, we derived our new equation utilizing: 1) partitioning of H+ buffering; 2) conservation of mass; and 3) acid-base equilibria. In validating this model, we compared the predicted equilibrium pH with the measured pH of an aqueous solution consisting of Na2HPO4 to which HCl was added. The measured pH values were in excellent agreement

  14. 12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

    Science.gov (United States)

    2010-01-01

    ... bank in “good faith” has not relied on stock as collateral. (a) The Board has received questions... “indirectly secured” by stock as indicated by the phrase, “if the lender, in good faith, has not relied upon...

  15. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

    DEFF Research Database (Denmark)

    Connolly, S. J.; Wallentin, L.; Ezekowitz, M. D.

    2013-01-01

    . There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY...

  16. Frugivorous bats maintain functional habitat connectivity in agricultural landscapes but rely strongly on natural forest fragments.

    Science.gov (United States)

    Ripperger, Simon P; Kalko, Elisabeth K V; Rodríguez-Herrera, Bernal; Mayer, Frieder; Tschapka, Marco

    2015-01-01

    Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae), a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.

  17. Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

    Science.gov (United States)

    Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

    2012-01-01

    Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

  18. Regulatory theory: commercially sustainable markets rely upon satisfying the public interest in obtaining credible goods.

    Science.gov (United States)

    Warren-Jones, Amanda

    2017-10-01

    Regulatory theory is premised on the failure of markets, prompting a focus on regulators and industry from economic perspectives. This article argues that overlooking the public interest in the sustainability of commercial markets risks markets failing completely. This point is exemplified through health care markets - meeting an essential need - and focuses upon innovative medicines as the most desired products in that market. If this seemingly invulnerable market risks failure, there is a pressing need to consider the public interest in sustainable markets within regulatory literature and practice. Innovative medicines are credence goods, meaning that the sustainability of the market fundamentally relies upon the public trusting regulators to vouch for product quality. Yet, quality is being eroded by patent bodies focused on economic benefits from market growth, rather than ensuring innovatory value. Remunerative bodies are not funding medicines relative to market value, and market authorisation bodies are not vouching for robust safety standards or confining market entry to products for 'unmet medical need'. Arguably, this failure to assure quality heightens the risk of the market failing where it cannot be substituted by the reputation or credibility of providers of goods and/or information such as health care professionals/institutions, patient groups or industry.

  19. Quality of record linkage in a highly automated cancer registry that relies on encrypted identity data

    Directory of Open Access Journals (Sweden)

    Schmidtmann, Irene

    2016-06-01

    Full Text Available Objectives: In the absence of unique ID numbers, cancer and other registries in Germany and elsewhere rely on identity data to link records pertaining to the same patient. These data are often encrypted to ensure privacy. Some record linkage errors unavoidably occur. These errors were quantified for the cancer registry of North Rhine Westphalia which uses encrypted identity data. Methods: A sample of records was drawn from the registry, record linkage information was included. In parallel, plain text data for these records were retrieved to generate a gold standard. Record linkage error frequencies in the cancer registry were determined by comparison of the results of the routine linkage with the gold standard. Error rates were projected to larger registries.Results: In the sample studied, the homonym error rate was 0.015%; the synonym error rate was 0.2%. The F-measure was 0.9921. Projection to larger databases indicated that for a realistic development the homonym error rate will be around 1%, the synonym error rate around 2%.Conclusion: Observed error rates are low. This shows that effective methods to standardize and improve the quality of the input data have been implemented. This is crucial to keep error rates low when the registry’s database grows. The planned inclusion of unique health insurance numbers is likely to further improve record linkage quality. Cancer registration entirely based on electronic notification of records can process large amounts of data with high quality of record linkage.

  20. Pneumococcal Competence Coordination Relies on a Cell-Contact Sensing Mechanism.

    Directory of Open Access Journals (Sweden)

    Marc Prudhomme

    2016-06-01

    Full Text Available Bacteria have evolved various inducible genetic programs to face many types of stress that challenge their growth and survival. Competence is one such program. It enables genetic transformation, a major horizontal gene transfer process. Competence development in liquid cultures of Streptococcus pneumoniae is synchronized within the whole cell population. This collective behavior is known to depend on an exported signaling Competence Stimulating Peptide (CSP, whose action generates a positive feedback loop. However, it is unclear how this CSP-dependent population switch is coordinated. By monitoring spontaneous competence development in real time during growth of four distinct pneumococcal lineages, we have found that competence shift in the population relies on a self-activated cell fraction that arises via a growth time-dependent mechanism. We demonstrate that CSP remains bound to cells during this event, and conclude that the rate of competence development corresponds to the propagation of competence by contact between activated and quiescent cells. We validated this two-step cell-contact sensing mechanism by measuring competence development during co-cultivation of strains with altered capacity to produce or respond to CSP. Finally, we found that the membrane protein ComD retains the CSP, limiting its free diffusion in the medium. We propose that competence initiator cells originate stochastically in response to stress, to form a distinct subpopulation that then transmits the CSP by cell-cell contact.

  1. Frugivorous bats maintain functional habitat connectivity in agricultural landscapes but rely strongly on natural forest fragments.

    Directory of Open Access Journals (Sweden)

    Simon P Ripperger

    Full Text Available Anthropogenic changes in land use threaten biodiversity and ecosystem functioning by the conversion of natural habitat into agricultural mosaic landscapes, often with drastic consequences for the associated fauna. The first step in the development of efficient conservation plans is to understand movement of animals through complex habitat mosaics. Therefore, we studied ranging behavior and habitat use in Dermanura watsoni (Phyllostomidae, a frugivorous bat species that is a valuable seed disperser in degraded ecosystems. Radio-tracking of sixteen bats showed that the animals strongly rely on natural forest. Day roosts were exclusively located within mature forest fragments. Selection ratios showed that the bats foraged selectively within the available habitat and positively selected natural forest. However, larger daily ranges were associated with higher use of degraded habitats. Home range geometry and composition of focal foraging areas indicated that wider ranging bats performed directional foraging bouts from natural to degraded forest sites traversing the matrix over distances of up to three hundred meters. This behavior demonstrates the potential of frugivorous bats to functionally connect fragmented areas by providing ecosystem services between natural and degraded sites, and highlights the need for conservation of natural habitat patches within agricultural landscapes that meet the roosting requirements of bats.

  2. Toward a Better Nutritional Aiding in Disasters: Relying on Lessons Learned during the Bam Earthquake.

    Science.gov (United States)

    Nekouie Moghadam, Mahmoud; Amiresmaieli, Mohammadreza; Hassibi, Mohammad; Doostan, Farideh; Khosravi, Sajad

    2017-08-01

    Introduction Examining various problems in the aftermath of disasters is very important to the disaster victims. Managing and coordinating food supply and its distribution among the victims is one of the most important problems after an earthquake. Therefore, the purpose of this study was to recognize problems and experiences in the field of nutritional aiding during an earthquake. This qualitative study was of phenomenological type. Using the purposive sampling method, 10 people who had experienced nutritional aiding during the Bam Earthquake (Iran; 2003) were interviewed. Colaizzi's method of analysis was used to analyze interview data. The findings of this study identified four main categories and 19 sub-categories concerning challenges in the nutritional aiding during the Bam Earthquake. The main topics included managerial, aiding, infrastructural, and administrative problems. The major problems in nutritional aiding include lack of prediction and development of a specific program of suitable nutritional pattern and nutritional assessment of the victims in critical conditions. Forming specialized teams, educating team members about nutrition, and making use of experts' knowledge are the most important steps to resolve these problems in the critical conditions; these measures are the duties of the relevant authorities. Nekouie Moghadam M , Amiresmaieli M , Hassibi M , Doostan F , Khosravi S . Toward a better nutritional aiding in disasters: relying on lessons learned during the Bam Earthquake. Prehosp Disaster Med. 2017;32(4):382-386.

  3. The Low Pitch of High-Frequency Complex Tones Relies on Temporal Fine Structure Information

    DEFF Research Database (Denmark)

    Santurette, Sébastien; Dau, Torsten

    2010-01-01

    High-frequency complex tones containing only unresolved harmonic components with a frequency spacing Δf usually evoke a low pitch equal to Δf. However, for inharmonic components, the low pitch is often found to deviate slightly from Δf. Whether this pitch shift relies exclusively on temporal fine...... structure (TFS) cues has been a matter of debate. It is also controversial up to which frequency TFS information remains available, and to what extent envelope cues become dominant as frequency increases. Using a pitch-matching paradigm, this study investigated whether the pitch of transposed tones.......5]. All stimuli were presented at 50 dB SPL in broadband pink-noise (13.5 dB/Hz at 1 kHz), and 40 matches per condition were obtained. For fenv = fc/11.5, the results favored hypothesis A for all values of fc, indicating that TFS cues are available and used for pitch extraction, up to at least 7 k...

  4. Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

    Science.gov (United States)

    Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

    2015-01-01

    Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

  5. Unparalleled sample treatment throughput for proteomics workflows relying on ultrasonic energy.

    Science.gov (United States)

    Jorge, Susana; Araújo, J E; Pimentel-Santos, F M; Branco, Jaime C; Santos, Hugo M; Lodeiro, Carlos; Capelo, J L

    2018-02-01

    We report on the new microplate horn ultrasonic device as a powerful tool to speed proteomics workflows with unparalleled throughput. 96 complex proteomes were digested at the same time in 4min. Variables such as ultrasonication time, ultrasonication amplitude, and protein to enzyme ratio were optimized. The "classic" method relying on overnight protein digestion (12h) and the sonoreactor-based method were also employed for comparative purposes. We found the protein digestion efficiency homogeneously distributed in the entire microplate horn surface using the following conditions: 4min sonication time and 25% amplitude. Using this approach, patients with lymphoma and myeloma were classified using principal component analysis and a 2D gel-mass spectrometry based approach. Furthermore, we demonstrate the excellent performance by using MALDI-mass spectrometry based profiling as a fast way to classify patients with rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis. Finally, the speed and simplicity of this method were demonstrated by clustering 90 patients with knee osteoarthritis disease (30), with a prosthesis (30, control group) and healthy individuals (30) with no history of joint disease. Overall, the new approach allows profiling a disease in just one week while allows to match the minimalism rules as outlined by Halls. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Laser-induced breakdown spectroscopy and chemometrics for classification of toys relying on toxic elements

    International Nuclear Information System (INIS)

    Godoi, Quienly; Leme, Flavio O.; Trevizan, Lilian C.; Pereira Filho, Edenir R.; Rufini, Iolanda A.; Santos, Dario; Krug, Francisco J.

    2011-01-01

    Quality control of toys for avoiding children exposure to potentially toxic elements is of utmost relevance and it is a common requirement in national and/or international norms for health and safety reasons. Laser-induced breakdown spectroscopy (LIBS) was recently evaluated at authors' laboratory for direct analysis of plastic toys and one of the main difficulties for the determination of Cd, Cr and Pb was the variety of mixtures and types of polymers. As most norms rely on migration (lixiviation) protocols, chemometric classification models from LIBS spectra were tested for sampling toys that present potential risk of Cd, Cr and Pb contamination. The classification models were generated from the emission spectra of 51 polymeric toys and by using Partial Least Squares - Discriminant Analysis (PLS-DA), Soft Independent Modeling of Class Analogy (SIMCA) and K-Nearest Neighbor (KNN). The classification models and validations were carried out with 40 and 11 test samples, respectively. Best results were obtained when KNN was used, with corrected predictions varying from 95% for Cd to 100% for Cr and Pb.

  7. Learning Similar Actions by Reinforcement or Sensory-Prediction Errors Rely on Distinct Physiological Mechanisms.

    Science.gov (United States)

    Uehara, Shintaro; Mawase, Firas; Celnik, Pablo

    2017-09-14

    Humans can acquire knowledge of new motor behavior via different forms of learning. The two forms most commonly studied have been the development of internal models based on sensory-prediction errors (error-based learning) and success-based feedback (reinforcement learning). Human behavioral studies suggest these are distinct learning processes, though the neurophysiological mechanisms that are involved have not been characterized. Here, we evaluated physiological markers from the cerebellum and the primary motor cortex (M1) using noninvasive brain stimulations while healthy participants trained finger-reaching tasks. We manipulated the extent to which subjects rely on error-based or reinforcement by providing either vector or binary feedback about task performance. Our results demonstrated a double dissociation where learning the task mainly via error-based mechanisms leads to cerebellar plasticity modifications but not long-term potentiation (LTP)-like plasticity changes in M1; while learning a similar action via reinforcement mechanisms elicited M1 LTP-like plasticity but not cerebellar plasticity changes. Our findings indicate that learning complex motor behavior is mediated by the interplay of different forms of learning, weighing distinct neural mechanisms in M1 and the cerebellum. Our study provides insights for designing effective interventions to enhance human motor learning. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Fruit production in three masting tree species does not rely on stored carbon reserves.

    Science.gov (United States)

    Hoch, Günter; Siegwolf, Rolf T W; Keel, Sonja G; Körner, Christian; Han, Qingmin

    2013-03-01

    Fruiting is typically considered to massively burden the seasonal carbon budget of trees. The cost of reproduction has therefore been suggested as a proximate factor explaining observed mast-fruiting patterns. Here, we used a large-scale, continuous (13)C labeling of mature, deciduous trees in a temperate Swiss forest to investigate to what extent fruit formation in three species with masting reproduction behavior (Carpinus betulus, Fagus sylvatica, Quercus petraea) relies on the import of stored carbon reserves. Using a free-air CO2 enrichment system, we exposed trees to (13)C-depleted CO2 during 8 consecutive years. By the end of this experiment, carbon reserve pools had significantly lower δ(13)C values compared to control trees. δ(13)C analysis of new biomass during the first season after termination of the CO2 enrichment allowed us to distinguish the sources of built-in carbon (old carbon reserves vs. current assimilates). Flowers and expanding leaves carried a significant (13)C label from old carbon stores. In contrast, fruits and vegetative infructescence tissues were exclusively produced from current, unlabeled photoassimilates in all three species, including F. sylvatica, which had a strong masting season. Analyses of δ(13)C in purified starch from xylem of fruit-bearing shoots revealed a complete turn-over of starch during the season, likely due to its usage for bud break. This study is the first to directly demonstrate that fruiting is independent from old carbon reserves in masting trees, with significant implications for mechanistic models that explain mast seeding.

  9. High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo.

    Directory of Open Access Journals (Sweden)

    Matthieu Y Pasco

    Full Text Available In multicellular organisms, insulin/IGF signaling (IIS plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz, a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome.

  10. The Integration of Realistic Episodic Memories Relies on Different Working Memory Processes: Evidence from Virtual Navigation

    Directory of Open Access Journals (Sweden)

    Gaën Plancher

    2018-01-01

    central elements. By contrast, the prevention of visuo-spatial maintenance interfered both with the encoding of the temporal context and with the binding. These results suggest that the integration of realistic episodic memories relies on different working memory processes that depend on the nature of the traces.

  11. The Integration of Realistic Episodic Memories Relies on Different Working Memory Processes: Evidence from Virtual Navigation.

    Science.gov (United States)

    Plancher, Gaën; Gyselinck, Valérie; Piolino, Pascale

    2018-01-01

    contrast, the prevention of visuo-spatial maintenance interfered both with the encoding of the temporal context and with the binding. These results suggest that the integration of realistic episodic memories relies on different working memory processes that depend on the nature of the traces.

  12. Object Categorization in Finer Levels Relies More on Higher Spatial Frequencies and Takes Longer.

    Science.gov (United States)

    Ashtiani, Matin N; Kheradpisheh, Saeed R; Masquelier, Timothée; Ganjtabesh, Mohammad

    2017-01-01

    The human visual system contains a hierarchical sequence of modules that take part in visual perception at different levels of abstraction, i.e., superordinate, basic, and subordinate levels. One important question is to identify the "entry" level at which the visual representation is commenced in the process of object recognition. For a long time, it was believed that the basic level had a temporal advantage over two others. This claim has been challenged recently. Here we used a series of psychophysics experiments, based on a rapid presentation paradigm, as well as two computational models, with bandpass filtered images of five object classes to study the processing order of the categorization levels. In these experiments, we investigated the type of visual information required for categorizing objects in each level by varying the spatial frequency bands of the input image. The results of our psychophysics experiments and computational models are consistent. They indicate that the different spatial frequency information had different effects on object categorization in each level. In the absence of high frequency information, subordinate and basic level categorization are performed less accurately, while the superordinate level is performed well. This means that low frequency information is sufficient for superordinate level, but not for the basic and subordinate levels. These finer levels rely more on high frequency information, which appears to take longer to be processed, leading to longer reaction times. Finally, to avoid the ceiling effect, we evaluated the robustness of the results by adding different amounts of noise to the input images and repeating the experiments. As expected, the categorization accuracy decreased and the reaction time increased significantly, but the trends were the same. This shows that our results are not due to a ceiling effect. The compatibility between our psychophysical and computational results suggests that the temporal

  13. Energetic solutions of Rock Sandpipers to harsh winter conditions rely on prey quality

    Science.gov (United States)

    Ruthrauff, Daniel R.; Dekinga, Anne; Gill, Robert E.; Piersma, Theunis

    2018-01-01

    Rock Sandpipers Calidris ptilocnemis have the most northerly non-breeding distribution of any shorebird in the Pacific Basin (upper Cook Inlet, Alaska; 61°N, 151°W). In terms of freezing temperatures, persistent winds and pervasive ice, this site is the harshest used by shorebirds during winter. We integrated physiological, metabolic, behavioural and environmental aspects of the non-breeding ecology of Rock Sandpipers at the northern extent of their range to determine the relative importance of these factors in facilitating their unique non-breeding ecology. Not surprisingly, estimated daily energetic demands were greatest during January, the coldest period of winter. These estimates were greatest for foraging birds, and exceeded basal metabolic rates by a factor of 6.5, a scope of increase that approaches the maximum sustained rate of energetic output by shorebirds during periods of migration, but far exceeds these periods in duration. We assessed the quality of their primary prey, the bivalve Macoma balthica, to determine the daily foraging duration required by Rock Sandpipers to satisfy such energetic demands. Based on size-specific estimates of M. balthica quality, Rock Sandpipers require over 13 h/day of foraging time in upper Cook Inlet in January, even when feeding on the highest quality prey. This range approaches the average daily duration of mudflat availability in this region (c. 18 h), a maximum value that annually decreases due to the accumulation of shore-fast ice. Rock Sandpipers are likely to maximize access to foraging sites by following the exposure of ice-free mudflats across the upper Cook Inlet region and by selecting smaller, higher quality M. balthica to minimize foraging times. Ultimately, this unusual non-breeding ecology relies on the high quality of their prey resources. Compared with other sites across their range, M. balthica from upper Cook Inlet have relatively light shells, potentially the result of the region

  14. You can't rely on color, yet we all do 2.0 (Manuscript Only)

    Science.gov (United States)

    van Nes, Floris L.

    2014-01-01

    Everybody views and uses color from early childhood onwards. But this magnificent property of all objects around us turns out to be elusive if you try to specify it and communicate it to another person. Also, people often don't know what effects color may have under different conditions. However, color is so important and omnipresent, that people can hardly avoid to 'rely on it' - so they do, in particular on its predictability. Thus, there is a discrepancy between the seeming self-evidence of color and the difficulty in specifying it accurately, for the prevailing circumstances. In order to analyze this situation, and possibly remedy it, a short historic perspective of the utilization and specification of color is given. The 'utilization' includes the emotional effects of color, which are important in, for instance, interior decorating but also play a role in literature and religion. 'Specification' begins with the early efforts by scientists, philosophers and artists to bring some order and understanding in what was observed with and while using color. Color has a number of basic functions: embellishment; attracting attention; coding; and bringing order in text by causing text parts presented in the same color to be judged as belonging together. People with a profession that involves color choices for many others, such as designers and manufacturers of products, including electronic visual displays, should have a fairly thorough knowledge of colorimetry and color perception. Unfortunately, they often don't, simply because for 'practitioners' whose work involves different aspects, applying color being only one of those, the available tools for specifying and applying color turn out to be too difficult to use. Two consequences of an insufficient knowledge of the effects color may have are given here. The first of these consequences, on color blindness, relates to 8% of the population, but the second one, on reading colored text, bears on everyone. Practical

  15. Konfuciānisma, daoisma un budisma mantojums Ķīnas tautas reliģijā

    OpenAIRE

    Dudaļeva, Jūlija

    2014-01-01

    Šī bakalaura darba nosaukums ir „Konfuciānisma, daoisma un budisma mantojums Ķīnas tautas reliģijā”. Nosaukums ķīniešu tautas reliģijas ir pētnieku izveidots, un tas neatbilst nevienam tradicionālam ķīniešu nosaukumam. Tautas reliģija ir brīvi strukturēts ticību, prakses, dievību, mītu un vērtību savienojums, kas ietver sevī elementus no senču dievkalpojumiem, mirušo kulta, dabas pielūgsmes, animisma, vietējām tradīcijām, daoisma, konfuciānisma un budisma. Darba mērķis ir izpētīt konfuciān...

  16. 16 CFR 1115.5 - Reporting of failures to comply with a voluntary consumer product safety standard relied upon by...

    Science.gov (United States)

    2010-01-01

    ... voluntary consumer product safety standard relied upon by the Commission under section 9 of the CPSA. 1115.5 Section 1115.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SUBSTANTIAL PRODUCT HAZARD REPORTS General Interpretation § 1115.5 Reporting of failures to comply...

  17. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    NARCIS (Netherlands)

    Schaafsma, Frederieke; Verbeek, Jos; Hulshof, Carel; van Dijk, Frank

    2005-01-01

    Background: Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM) promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based

  18. 78 FR 29392 - Embedded Digital Devices in Safety-Related Systems, Systems Important to Safety, and Items Relied...

    Science.gov (United States)

    2013-05-20

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0098] Embedded Digital Devices in Safety-Related Systems, Systems Important to Safety, and Items Relied on for Safety AGENCY: Nuclear Regulatory Commission. ACTION... (NRC) is issuing for public comment Draft Regulatory Issue Summary (RIS) 2013-XX, ``Embedded Digital...

  19. Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation : insights from the RE-LY trial

    NARCIS (Netherlands)

    Westenbrink, B. D.; Alings, M.; Connolly, S. J.; Eikelboom, J.; Ezekowitz, M. D.; Oldgren, J.; Yang, S.; Pongue, J.; Yusuf, S.; Wallentin, L.; van Gilst, W. H.

    BackgroundAnemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). ObjectivesTo investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. Patients and methodsWe retrospectively analyzed the RE-LY

  20. Immobilization of α-Amylase from Anoxybacillus sp. SK3-4 on ReliZyme and Immobead Supports

    Directory of Open Access Journals (Sweden)

    Ummirul Mukminin Kahar

    2016-09-01

    Full Text Available α-Amylase from Anoxybacillus sp. SK3-4 (ASKA is a thermostable enzyme that produces a high level of maltose from starches. A truncated ASKA (TASKA variant with improved expression and purification efficiency was characterized in an earlier study. In this work, TASKA was purified and immobilized through covalent attachment on three epoxide (ReliZyme EP403/M, Immobead IB-150P, and Immobead IB-150A and an amino-epoxide (ReliZyme HFA403/M activated supports. Several parameters affecting immobilization were analyzed, including the pH, temperature, and quantity (mg of enzyme added per gram of support. The influence of the carrier surface properties, pore sizes, and lengths of spacer arms (functional groups on biocatalyst performances were studied. Free and immobilized TASKAs were stable at pH 6.0–9.0 and active at pH 8.0. The enzyme showed optimal activity and considerable stability at 60 °C. Immobilized TASKA retained 50% of its initial activity after 5–12 cycles of reuse. Upon degradation of starches and amylose, only immobilized TASKA on ReliZyme HFA403/M has comparable hydrolytic ability with the free enzyme. To the best of our knowledge, this is the first report of an immobilization study of an α-amylase from Anoxybacillus spp. and the first report of α-amylase immobilization using ReliZyme and Immobeads as supports.

  1. Invitro genotoxicity, assessment of cytotoxicity and of Rely X luting cement on human lymphocyte cells before and after irradiation

    International Nuclear Information System (INIS)

    Shetty, Shilpa S.; Hegde, Mithra N.; Shabin; Hegde, Nidarsh D.; Suchetha Kumari; Sanjeev, Ganesh

    2013-01-01

    In dentistry, a luting agent is a viscous material placed between tooth structure and a prosthesis that by polymerization firmly attach the prosthesis to the tooth structure. Luting agents contact a large area of dentin when used for crown cementation. There is little information on biocompatibility tests, especially on the effect of electron beam irradiation on cytotoxicity for luting resin cements. To determine the in vitro cytotoxicity and genotoxicity of Rely X luting cement on human lymphocyte cells before and after irradiation. Rely X luting cement was obtained commercially. Samples were prepared as per the ISO standard size of 25x2x2 mm using polytetrafluoroethylene teflon mould and divided into two groups - non irradiated and irradiated groups. The samples in irradiated category were exposed to 200 Gy of electron beam irradiation at Microtron Centre, Mangalore University, Mangalore, India. For hemolysis the samples were immersed in phosphate buffer saline and incubated at 370℃ for 24 hrs, 7 days and 14 days. 200 μl of 24 hr material extract was mixed with human peripheral blood lymphocyte tested for comet assay by single cell DNA comet assay. Hemolytic activity of non irradiated Rely X luting cement after 24 hrs, 7 days and 14 days was 54.78±1.48, 69.91±2.41 and 43.21±0.92 respectively whereas hemolytic activity of irradiated Rely X luting cement after 24 hrs, 7 days and 14 days was 91.8±8.29, 56.95±19.7 and 41.34±12.30. The irradiation of Rely X luting cement with 200 Gy dose of electron beam irradiation caused an increase in the frequency of DNA damage when compared to that of the non-irradiated group. Based on the experimental condition, it is concluded that incomplete polymerization of the dental luting cements has resulted in the elution of the resin components which are responsible for the cytotoxicity and genotoxicity of Rely X luting cement on human lymphocyte cells. (author)

  2. Rely-Guarantee Protocols

    Science.gov (United States)

    2014-05-01

    University Pittsburgh, PA 15213 1School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. 2Faculdade de Ciências e Tecnologia ...additional examples that are not in the ECOOP paper. This work was partially supported by Fundação para a Ciência e Tecnologia (Portuguese Foundation

  3. Einfluss von Flüssigkeitskontamination auf die Verbundfestigkeit von Wurzelkanalsealern (Adseal und RelyX Unicem)

    OpenAIRE

    Höfer, Margarita

    2010-01-01

    Ziel dieser Arbeit war es, eine Aussage über die Verbundfestigkeit des epoxidharz-basierten Wurzelkanalsealers Adseal und des selbstadhäsiven methacrylatbasierten Befestigungszements RelyX Unicem zum Wurzelkanaldentin in Abhängigkeit vom Verbleib der Spülflüssigkeit im Wurzelkanal zu treffen. Die Kontamination des Wurzelkanals wurde mittels dreier verschiedener Spüllösungen durchgeführt. Zu diesem Zweck wurden Scherfestigkeitsmessungen sowie lichtmikroskopische Untersuchungen der Sealer-Sprea...

  4. Phonological memory in sign language relies on the visuomotor neural system outside the left hemisphere language network.

    Science.gov (United States)

    Kanazawa, Yuji; Nakamura, Kimihiro; Ishii, Toru; Aso, Toshihiko; Yamazaki, Hiroshi; Omori, Koichi

    2017-01-01

    Sign language is an essential medium for everyday social interaction for deaf people and plays a critical role in verbal learning. In particular, language development in those people should heavily rely on the verbal short-term memory (STM) via sign language. Most previous studies compared neural activations during signed language processing in deaf signers and those during spoken language processing in hearing speakers. For sign language users, it thus remains unclear how visuospatial inputs are converted into the verbal STM operating in the left-hemisphere language network. Using functional magnetic resonance imaging, the present study investigated neural activation while bilinguals of spoken and signed language were engaged in a sequence memory span task. On each trial, participants viewed a nonsense syllable sequence presented either as written letters or as fingerspelling (4-7 syllables in length) and then held the syllable sequence for 12 s. Behavioral analysis revealed that participants relied on phonological memory while holding verbal information regardless of the type of input modality. At the neural level, this maintenance stage broadly activated the left-hemisphere language network, including the inferior frontal gyrus, supplementary motor area, superior temporal gyrus and inferior parietal lobule, for both letter and fingerspelling conditions. Interestingly, while most participants reported that they relied on phonological memory during maintenance, direct comparisons between letters and fingers revealed strikingly different patterns of neural activation during the same period. Namely, the effortful maintenance of fingerspelling inputs relative to letter inputs activated the left superior parietal lobule and dorsal premotor area, i.e., brain regions known to play a role in visuomotor analysis of hand/arm movements. These findings suggest that the dorsal visuomotor neural system subserves verbal learning via sign language by relaying gestural inputs to

  5. Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity: in silico bioinformatic step-by-step guide using quantitative structure-activity relationships.

    Science.gov (United States)

    Hattotuwagama, Channa K; Doytchinova, Irini A; Flower, Darren R

    2007-01-01

    Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method

  6. Influence of Computerized Sounding Out on Spelling Performance for Children who do and not rely on AAC

    Science.gov (United States)

    McCarthy, Jillian H.; Hogan, Tiffany P.; Beukelman, David R.; Schwarz, Ilsa E.

    2015-01-01

    Purpose Spelling is an important skill for individuals who rely on augmentative alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Methods Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. Results The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. Conclusion The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed. PMID:24512195

  7. Humans rely on the same rules to assess emotional valence and intensity in conspecific and dog vocalizations.

    Science.gov (United States)

    Faragó, Tamás; Andics, Attila; Devecseri, Viktor; Kis, Anna; Gácsi, Márta; Miklósi, Adám

    2014-01-01

    Humans excel at assessing conspecific emotional valence and intensity, based solely on non-verbal vocal bursts that are also common in other mammals. It is not known, however, whether human listeners rely on similar acoustic cues to assess emotional content in conspecific and heterospecific vocalizations, and which acoustical parameters affect their performance. Here, for the first time, we directly compared the emotional valence and intensity perception of dog and human non-verbal vocalizations. We revealed similar relationships between acoustic features and emotional valence and intensity ratings of human and dog vocalizations: those with shorter call lengths were rated as more positive, whereas those with a higher pitch were rated as more intense. Our findings demonstrate that humans rate conspecific emotional vocalizations along basic acoustic rules, and that they apply similar rules when processing dog vocal expressions. This suggests that humans may utilize similar mental mechanisms for recognizing human and heterospecific vocal emotions.

  8. Can we rely on the antiretroviral treatment as the only means for human immunodeficiency virusprevention? A Public Health perspective.

    Science.gov (United States)

    Mozalevskis, Antons; Manzanares-Laya, Sandra; García de Olalla, Patricia; Moreno, Antonio; Jacques-Aviñó, Constanza; Caylà, Joan A

    2015-11-01

    The evidence that supports the preventive effect of combination antiretroviral treatment (cART) in HIV sexual transmission suggested the so-called 'treatment as prevention' (TAP) strategy as a promising tool for slowing down HIV transmission. As the messages and attitudes towards condom use in the context of TAP appear to be somehow confusing, the aim here is to assess whether relying on cART alone to prevent HIV transmission can currently be recommended from the Public Health perspective. A review is made of the literature on the effects of TAP strategy on HIV transmission and the epidemiology of other sexual transmitted infections (STIs) in the cART era, and recommendations from Public Health institutions on the TAP as of February 2014. The evolution of HIV and other STIs in Barcelona from 2007 to 2012 has also been analysed. Given that the widespread use of cART has coincided with an increasing incidence of HIV and other STIs, mainly amongst men who have sex with men, a combination and diversified prevention methods should always be considered and recommended in counselling. An informed decision on whether to stop using condoms should only be made by partners within stable couples, and after receiving all the up-to-date information regarding TAP. From the public health perspective, primary prevention should be a priority; therefore relying on cART alone is not a sufficient strategy to prevent new HIV and other STIs. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Social plasticity relies on different neuroplasticity mechanisms across the brain social decision-making network in zebrafish

    Directory of Open Access Journals (Sweden)

    Magda C Teles

    2016-02-01

    Full Text Available Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2 as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod. Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e. Winners, Losers and Mirror-fighters present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g. BDNF in the dorsolateral telencephalon, which is a putative teleost homologue of the mammalian hippocampus. Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These

  10. Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish.

    Science.gov (United States)

    Teles, Magda C; Cardoso, Sara D; Oliveira, Rui F

    2016-01-01

    Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results

  11. Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish

    Science.gov (United States)

    Teles, Magda C.; Cardoso, Sara D.; Oliveira, Rui F.

    2016-01-01

    Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results

  12. Influence of computerized sounding out on spelling performance for children who do and do not rely on AAC.

    Science.gov (United States)

    McCarthy, Jillian H; Hogan, Tiffany P; Beukelman, David R; Schwarz, Ilsa E

    2015-05-01

    Spelling is an important skill for individuals who rely on augmentative and alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed. We investigated how computerized sounding out influenced spelling accuracy of pseudowords for children with complex communication needs who did and did not use augmentative and alternative communication (AAC). Results indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words by participants, suggesting that computerized sounding out might assist in more accurate spelling for children who use AAC. Future research is needed to determine how language and reading abilities influence the use of computerized sounding out with children who have a range of speech intelligibility abilities and do and do not use AAC.

  13. Catalytic ozonation not relying on hydroxyl radical oxidation: A selective and competitive reaction process related to metal-carboxylate complexes

    KAUST Repository

    Zhang, Tao

    2014-01-01

    Catalytic ozonation following non-hydroxyl radical pathway is an important technique not only to degrade refractory carboxylic-containing organic compounds/matter but also to avoid catalyst deactivation caused by metal-carboxylate complexation. It is unknown whether this process is effective for all carboxylates or selective to special molecule structures. In this work, the selectivity was confirmed using O3/(CuO/CeO2) and six distinct ozone-resistant probe carboxylates (i.e., acetate, citrate, malonate, oxalate, pyruvate and succinate). Among these probe compounds, pyruvate, oxalate, and citrate were readily degraded following the rate order of oxalate>citrate>pyruvate, while the degradation of acetate, malonate, and succinate was not promoted. The selectivity was independent on carboxylate group number of the probe compounds and solution pH. Competitive degradation was observed for carboxylate mixtures following the preference order of citrate, oxalate, and finally pyruvate. The competitive degradation was ascribed to competitive adsorption on the catalyst surface. It was revealed that the catalytically degradable compounds formed bidentate chelating or bridging complexes with surface copper sites of the catalyst, i.e., the active sites. The catalytically undegradable carboxylates formed monodentate complexes with surface copper sites or just electrostatically adsorbed on the catalyst surface. The selectivity, relying on the structure of surface metal-carboxylate complex, should be considered in the design of catalytic ozonation process. © 2013 Elsevier B.V.

  14. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    Science.gov (United States)

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  15. Sociological investigation Students of Universities' Social-Political Trust in Iran: relying on secondary analysis of some national surveys

    Directory of Open Access Journals (Sweden)

    Sayed Mahdi Etemadifard

    2013-12-01

    Full Text Available Social system based on mutual trust among members continues to exist. Social trust in modem era is more important than earlier periods. Subject of current report is focused on the trust of Iranian students in different aspects. Main question in this investigation is about social-political trust of these students (based on trust in Islamic Republic of Iran at the past and present. This matter explored by secondary analysis of data, Relying on secondary analysis of some national surveys. Based on data and consequences of other researches we are going to illustrate the objective aspects of student's trust in current decades. The main sources for data collection at this stage include: All the public surveys conducted in the past four decades, the general data about students and their related assays. Trust students were evaluated on the following dimensions: trust in trade unions and various groups, trust in the clergy, directors of public trust and confidence in judges. Furthermore, the level of political engagement and participation in elections, satisfaction with economic situation, political situation and level of satisfaction with confidence in radio and television news. Reduction of public trust leads to reduced maximum student trust especially in the social and political dimensions.

  16. The perception of (naked only) bodies and faceless heads relies on holistic processing: Evidence from the inversion effect.

    Science.gov (United States)

    Bonemei, Rob; Costantino, Andrea I; Battistel, Ilenia; Rivolta, Davide

    2018-05-01

    Faces and bodies are more difficult to perceive when presented inverted than when presented upright (i.e., stimulus inversion effect), an effect that has been attributed to the disruption of holistic processing. The features that can trigger holistic processing in faces and bodies, however, still remain elusive. In this study, using a sequential matching task, we tested whether stimulus inversion affects various categories of visual stimuli: faces, faceless heads, faceless heads in body context, headless bodies naked, whole bodies naked, headless bodies clothed, and whole bodies clothed. Both accuracy and inversion efficiency score results show inversion effects for all categories but for clothed bodies (with and without heads). In addition, the magnitude of the inversion effect for face, naked body, and faceless heads was similar. Our findings demonstrate that the perception of faces, faceless heads, and naked bodies relies on holistic processing. Clothed bodies (with and without heads), on the other side, may trigger clothes-sensitive rather than body-sensitive perceptual mechanisms. © 2017 The British Psychological Society.

  17. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    Science.gov (United States)

    Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

    2017-02-01

    It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

  18. Symmetric Encryption Relying on Chaotic Henon System for Secure Hardware-Friendly Wireless Communication of Implantable Medical Systems

    Directory of Open Access Journals (Sweden)

    Taha Belkhouja

    2018-05-01

    Full Text Available Healthcare remote devices are recognized as a promising technology for treating health related issues. Among them are the wireless Implantable Medical Devices (IMDs: These electronic devices are manufactured to treat, monitor, support or replace defected vital organs while being implanted in the human body. Thus, they play a critical role in healing and even saving lives. Current IMDs research trends concentrate on their medical reliability. However, deploying wireless technology in such applications without considering security measures may offer adversaries an easy way to compromise them. With the aim to secure these devices, we explore a new scheme that creates symmetric encryption keys to encrypt the wireless communication portion. We will rely on chaotic systems to obtain a synchronized Pseudo-Random key. The latter will be generated separately in the system in such a way that avoids a wireless key exchange, thus protecting patients from the key theft. Once the key is defined, a simple encryption system that we propose in this paper will be used. We analyze the performance of this system from a cryptographic point of view to ensure that it offers a better safety and protection for patients.

  19. Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1 as Predictors for Response to Interferon Therapy in HCV Genotype 4

    Directory of Open Access Journals (Sweden)

    Olfat Shaker

    2013-01-01

    Full Text Available Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66% of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1*0313 allele and DRB1*04-DRB1*11, DQB1*0204-DQB1*0313, DQB1*0309-DQB1*0313, and DQB1*0313-DQB1*0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1*02, DQB1*06, DRB1*13, and DRB1*15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1*1301, DRB1*1361, and DRB1*1369 alleles and DRB1*1301-DRB1*1328, DRB1*1301-DRB1*1361, DRB1*1301-DRB1*1369, DRB1*1328-DRB1*1361, and DRB1*1328-DRB1*1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

  20. Evidence of HLA-DQB1 Contribution to Susceptibility of Dengue Serotype 3 in Dengue Patients in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Daniela Maria Cardozo

    2014-01-01

    Full Text Available Dengue infection (DI transmitted by arthropod vectors is the viral disease with the highest incidence throughout the world, an estimated 300 million cases per year. In addition to environmental factors, genetic factors may also influence the manifestation of the disease; as even in endemic areas, only a small proportion of people develop the most serious form. Immune-response gene polymorphisms may be associated with the development of cases of DI. The aim of this study was to determine allele frequencies in the HLA-A, B, C, DRB1, DQA1, and DQB1 loci in a Southern Brazil population with dengue virus serotype 3, confirmed by the ELISA serological method, and a control group. The identification of the HLA alleles was carried out using the SSO genotyping PCR program (One Lambda, based on Luminex technology. In conclusion, this study suggests that DQB1*06:11 allele could act as susceptible factors to dengue virus serotype 3, while HLA-DRB1*11 and DQA1*05:01 could act as resistance factors.

  1. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    Directory of Open Access Journals (Sweden)

    Hulshof Carel

    2005-08-01

    Full Text Available Abstract Background Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based practice and EBM we compared professional advice on occupational health topics with best evidence from the literature. Methods We asked 14 occupational physicians to consult their usual information sources on 12 pre-conceived occupational health problems. The problems were presented in the form of case vignettes which contained sufficient clinical information to be used by the occupational physicians for the consultation of their experts. We had searched the literature for the best available evidence on the 12 problems, which made it possible to answer the clinical questions with a clear yes or no. Results The cases could be used by the occupational physicians as arising from their own practice. All together the occupational physicians consulted 75 different experts. Almost half of the consulted experts were near colleagues, 10% were industrial hygienists, 8% medical specialists and the rest had a varied background. Fifty three percent (95% confidence interval 42% to 65% of all professional advice was not in line with the research literature. In 18 cases (24% professional advice explicitly referred to up-to-date research literature as their used source. These cases were substantially less incorrect (17% than advice that had not mentioned the literature as a source (65% (difference 48%, 95% Confidence Interval from 27% to 69%. Conclusion Advice that occupational physicians routinely get in their daily practice differs substantially from best evidence from the literature. Occupational physicians who ask professional advice should always ask about the evidence of this advice.

  2. Caution required when relying on a colleague's advice; a comparison between professional advice and evidence from the literature

    Science.gov (United States)

    Schaafsma, Frederieke; Verbeek, Jos; Hulshof, Carel; van Dijk, Frank

    2005-01-01

    Background Occupational Physicians rely especially on advice from colleagues when answering their information demands. On the other hand, Evidence-based Medicine (EBM) promotes the use of up-to-date research literature instead of experts. To find out if there was a difference between expert-based practice and EBM we compared professional advice on occupational health topics with best evidence from the literature. Methods We asked 14 occupational physicians to consult their usual information sources on 12 pre-conceived occupational health problems. The problems were presented in the form of case vignettes which contained sufficient clinical information to be used by the occupational physicians for the consultation of their experts. We had searched the literature for the best available evidence on the 12 problems, which made it possible to answer the clinical questions with a clear yes or no. Results The cases could be used by the occupational physicians as arising from their own practice. All together the occupational physicians consulted 75 different experts. Almost half of the consulted experts were near colleagues, 10% were industrial hygienists, 8% medical specialists and the rest had a varied background. Fifty three percent (95% confidence interval 42% to 65%) of all professional advice was not in line with the research literature. In 18 cases (24%) professional advice explicitly referred to up-to-date research literature as their used source. These cases were substantially less incorrect (17%) than advice that had not mentioned the literature as a source (65%) (difference 48%, 95% Confidence Interval from 27% to 69%). Conclusion Advice that occupational physicians routinely get in their daily practice differs substantially from best evidence from the literature. Occupational physicians who ask professional advice should always ask about the evidence of this advice. PMID:16131405

  3. Access to Grafts in a Liver Transplant Center: Does It Rely on the Severity of the Waiting List Population?

    Science.gov (United States)

    Daciuk, N I; Quiñonez, E G; Poupard, M; Vergara Sandoval, R M; Mattera, F J

    2018-03-01

    The number of transplants performed relies, partially, on recipients' variables on the waiting list. The goal of this study was to compare recipients from a high-volume liver center in Argentina with the rest of the country. This study was a retrospective analysis of liver transplant recipients nationally between January 2013 and April 2017. It involved extracting data from the open database CRESI-SINTRA (the Argentinian database of the National Procurement Organization, an equivalent to the United Network for Organ Sharing); expressing results by percentages, medians, and interquartile ranges (IQRs); and comparing the national population with the population transplanted at Hospital El Cruce (HEC). The Mann-Whitney U test was used for analysis. Nationally, 1434 liver transplants were performed. A total of 177 (12.34%) were emergency status; 811 (56.6%) were by the Model for End-Stage Liver Disease (MELD) (n = 759)/PELD (Pediatric End-Stage Liver Disease) (n = 52), with a median graft assignment position of 5 (IQR, 3-10) in 57.2 days (IQR, 11-217). Median MELD access was 29 points (IQR, 24-33). A total of 446 (31.1%) had MELD exceptions; 249 (55.8%) of these were due to Milan hepatocellular carcinoma. At the HEC, 167 liver transplantations were performed; 26 (15.6%) were emergency status and 97 (58.1%) by MELD (none PELD). Their median graft assignment position was 4 (IQR, 4-16) in 19.1 days (IQR, 4-90); median MELD access was 28 points (IQR, 24-31). Forty-five patients (26.9%) had MELD exceptions; 31 (68.9%) were due to hepatocellular carcinoma. Our center has a larger proportion of recipients transplanted by emergency status and MELD, similar MELD access, and less waiting list time, reflecting our wide policy of liver graft acceptance. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

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    Abolfazl Akbari

    2016-10-01

    Full Text Available Vitamin C (L-ascorbic acid or ascorbate is a biomolecule that participates in many biochemical processes. It is an essential nutrient for humans, however, in some species such as rodents and guinea pigs is synthesized. It has a variety of functions in the body that we might venture to say make it a very important antioxidant nature and pro-oxidant. L-ascorbic acidic a reduced form of vitamin C and dehydroascorbic acid (DHA is the oxidized form of ascorbate, both L-ascorbic acid and dihydroascorbic acid retain the vitamin C activity. Dehydro-ascorbate is reconverted to ascorbate in the cytosol by cytochrome b reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Ascorbate is transported into the cell via the sodium-dependent vitamin C transporters (SVCTs, which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters family (GLUTs. The highest concentrations of ascorbate in the body are found in brain and adrenal gland. Vitamin C also acts as a co-factor in several enzyme reactions. This vitamin is an essential biochemical factor in the reproductive process. The pharmacophore of vitamin C is the ascorbate, ascorbate is an antioxidant.Ascorbate is a neuromodulator of glutamatergic and dopaminergic system and related behaviors. It also improves components of the immune system. Given the wide role of ascorbate, further investigation is necessary to evaluate the exact mechanism(s underlying these effects. In this review we will consider a short overview of the characteristics and function of vitamin C (relying on antioxidant function in various tissues.

  5. Polymorphism of leukocyte and erythrocyte antigens in chronic kidney disease patients in southern Brazil.

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    Roger Haruki Yamakawa

    Full Text Available We investigated the polymorphism of human leukocyte antigens (HLA and Duffy erythrocyte antigens in chronic kidney disease (CKD patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType®SSO (One Lambda, Inc.. Duffy phenotypes were determined by gel column agglutination using anti-Fy(a and anti-Fy(b monoclonal anti-sera. The patients' predominant ages ranged between 51 and 70 years (43% and the predominant gender, ethnic group and dialysis period were, respectively, male (62%, white (62% and 1-3 years (40%. The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+ and Fy(a-b-, respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b- phenotype (p<0.0001, OR = 2.56, 95% CI = 1.60-4.07 was the most frequent in the patients (p<0.05, and the Fy(a+b+ phenotype (p = 0.0039, OR = 1.71, 95% CI = 1.18-2.51 was the most frequent in the healthy subjects in the same region of Paraná state (p<0.05. Regarding HLA, the HLA-B*42, -B*45, -B*51 and -DRB1*03 allele groups were the most frequent in the patients (p<0.05, and the HLA-B*44 allele group was the most frequent in the healthy subjects in the same region of Brazil (p<0.05. The polymorphism of these two markers among CKD patients in southern Brazil and healthy subjects of other studies, suggests that these markers might be involved with CKD development. Further studies should be undertaken to analyze the markers' influence on CKD and the long-term results from kidney transplantation.

  6. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

    Science.gov (United States)

    Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

    2012-08-07

    The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

  7. Reliģijas, apmierinātības ar dzīvi un pašvērtējuma saistība.

    OpenAIRE

    Bērziņa, Annija

    2015-01-01

    Šī darba mērķis ir noskaidrot saistību starp reliģiju, apmierinātību ar dzīvi un pašvērtējumu. Apmierinātība ar dzīvi sevī ietver laimi, subjektīvo labklājību un pozitīvas emocijas. Šī darba ietvaros vairāk tiks apskatīta subjektīvā labklājība. Reliģija ir ticība kam mistiskam , kas sevī ietver reliģisku normu ievērošanu, rituālus, ticību un būšanu reliģiskā kopienā. Starp subjektīvo labklājību un reliģiju pastāv pozitīva korelācija. Pašvērtējums ir cilvēka subjektīvs viedoklis par...

  8. 12 CFR 714.5 - What is required if you rely on an estimated residual value greater than 25% of the original cost...

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What is required if you rely on an estimated residual value greater than 25% of the original cost of the leased property? 714.5 Section 714.5 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.5 What is...

  9. Research Advances: Pacific Northwest National Laboratory Finds New Way to Detect Destructive Enzyme Activity--Hair Dye Relies on Nanotechnology--Ways to Increase Shelf Life of Milk

    Science.gov (United States)

    King, Angela G.

    2007-01-01

    Recent advances in various research fields are described. Scientists at the Pacific Northwest National Laboratory have found a new way to detect destructive enzyme activity, scientists in France have found that an ancient hair dye used by ancient people in Greece and Rome relied on nanotechnology and in the U.S. scientists are developing new…

  10. [Zeme, vara un reliģija viduslaikos un jaunajas laikos Baltijas jūras reģionā] / Marija Golubeva

    Index Scriptorium Estoniae

    Golubeva, Marija, 1973-

    2011-01-01

    Arvustus: Zeme, vara un reliģija viduslaikos un jaunajas laikos Baltijas jūras reģionā / Hrsg. von Andris Šnē. Acta Universitatis Latviensis ; 725. (Riga: Verlag Latvijas Universitātes Akadēmiskais apgāds, 2009)

  11. Biological adhesion of the flatworm Macrostomum lignano relies on a duo-gland system and is mediated by a cell type-specific intermediate filament protein

    NARCIS (Netherlands)

    Lengerer, Birgit; Pjeta, Robert; Wunderer, Julia; Rodrigues, Marcelo; Arbore, Roberto; Schaerer, Lukas; Berezikov, Eugene; Hess, Michael W.; Pfaller, Kristian; Egger, Bernhard; Obwegeser, Sabrina; Salvenmoser, Willi; Ladurner, Peter

    2014-01-01

    Background: Free-living flatworms, in both marine and freshwater environments, are able to adhere to and release from a substrate several times within a second. This reversible adhesion relies on adhesive organs comprised of three cell types: an adhesive gland cell, a releasing gland cell, and an

  12. Dgroup: DG02662 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG02662 Chemical ... DGroup Apolizumab ... D02967 ... Apolizumab (USAN/INN) ... Antineoplastic, Anti-HLA-DR antibody... Monoclonal antibody HLA-DRB [HSA:3123 3125 3126 3127] [KO:K06752] ...

  13. Lying relies on the truth

    NARCIS (Netherlands)

    Debey, E.; De Houwer, J.; Verschuere, B.

    2014-01-01

    Cognitive models of deception focus on the conflict-inducing nature of the truth activation during lying. Here we tested the counterintuitive hypothesis that the truth can also serve a functional role in the act of lying. More specifically, we examined whether the construction of a lie can involve a

  14. The link between some alleles on human leukocyte antigen system and autism in children.

    Science.gov (United States)

    Mostafa, Gehan A; Shehab, Abeer A; Al-Ayadhi, Laila Y

    2013-02-15

    The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Polymorphism of HLA in the Romanian population.

    Science.gov (United States)

    Reed, E; Ho, E; Lupu, F; McManus, P; Vasilescu, R; Foca-Rodi, A; Suciu-Foca, N

    1992-01-01

    We have investigated the HLA-class I and class II polymorphism in a population of 83 Romanians using conventional serology together with PCR amplification and oligonucleotide typing of HLA-class II genes. Romanians show a higher frequency of HLA-A11, B13, B18, B37, B39, B51 and DR2 than other European populations. HLA-DRB1*1501 and 1601 account for the high frequency of the serologic specificity DR2. In Romanians, HLA-DR2 is in linkage disequilibrium with HLA-B18 and HLA-Bw52 rather than with HLA-B7 as in the case in other Europeans. Unexpected HLA-DR2 haplotypes include HLA-DRB1*1502, DQA1*0102, DQB1*0601; HLA-DRB1*1602, DQA1*0102, DQB1*0502. Other unusual haplotypes include HLA-DRB1*0405, DQA1*03, DQB1*0302; HLA-DRB1*1305, DQA1*0103, DQB1*0603; and HLA-DRB1*1405, DQA1*0101, DQB1*05032. Analysis of the genetic distance between Romanians and other Europeans who have been studied serologically are consistent with the hypothesis that Romanians descend from Roman ancestors who colonized Dacia between the 1st century B.C. and 1st century A.D.

  16. Cytotoxicity Comparison of Harvard Zinc Phosphate Cement Versus Panavia F2 and Rely X Plus Resin Cements on Rat L929-fibroblasts.

    Science.gov (United States)

    Mahasti, Sahabi; Sattari, Mandana; Romoozi, Elham; Akbar-Zadeh Baghban, Alireza

    2011-01-01

    Resin cements, regardless of their biocompatibility, have been widely used in restorative dentistry during the recent years. These cements contain hydroxy ethyl methacrylate (HEMA) molecules which are claimed to penetrate into dentinal tubules and may affect dental pulp. Since tooth preparation for metal ceramic restorations involves a large surface of the tooth, cytotoxicity of these cements would be more important in fixed prosthodontic treatments. The purpose of this study was to compare the cytotoxicity of two resin cements (Panavia F2 and Rely X Plus) versus zinc phosphate cement (Harvard) using rat L929-fibroblasts in vitro. In this experimental study, ninety hollow glass cylinders (internal diameter 5-mm, height 2-mm) were made and divided into three groups. Each group was filled with one of three experimental cements; Harvard Zinc Phosphate cement, Panavia F2 resin cement and Rely X Plus resin cement. L929- Fibroblast were passaged and subsequently cultured in 6-well plates of 5×10(5) cells each. The culture medium was RPMI_ 1640. All samples were incubated in CO2. Using enzyme-linked immune-sorbent assay (ELISA) and (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) (MTT) assay, the cytotoxicity of the cements was investigated at 1 hour, 24 hours and one week post exposure. Statistical analyses were performed via two-way ANOVA and honestly significant difference (HSD) Tukey tests. This study revealed significant differences between the three cements at the different time intervals. Harvard cement displayed the greatest cytotoxicity at all three intervals. After 1 hour Panavia F2 showed the next greatest cytotoxicity, but after 24-hours and oneweek intervals Rely X Plus showed the next greatest cytotoxicity. The results further showed that cytotoxicity decreased significantly in the Panavia F2 group with time (pHarvard cement group failed to showed no noticeable change in cytotoxicity with time. Although this study has limitations, it provides

  17. The description-experience gap and its relation to instructional control: Do people rely more on their experience than in objective descriptions?

    Directory of Open Access Journals (Sweden)

    Álvaro Viúdez

    2017-11-01

    Full Text Available The present work aims to reveal contradictory results obtained on two different fields; particularly from two studies conducted on the description-experience gap field showing that descriptions are neglected when personal experience is available (1,2, and several others conducted on the instructional control field getting to the opposite conclusion (3–8. To account for this contradiction, we hypothesized that participants from the studies of Jessup, Bishara and Busemeyer (1 and Lejarraga and Gonzalez (2 relied on their experience rather than on the descriptions because of the difficult, demanding nature of the probabilistic descriptions they faced. Enriched descriptions were created in our experiment to assess the contribution of this factor to the differential influence of the descriptions in choice behavior. Nonetheless, our hypothesis did not find support in the results and further research is needed to account for the aforementioned contradiction.

  18. Imputation of missing genotypes within LD-blocks relying on the basic coalescent and beyond: consideration of population growth and structure.

    Science.gov (United States)

    Kabisch, Maria; Hamann, Ute; Lorenzo Bermejo, Justo

    2017-10-17

    Genotypes not directly measured in genetic studies are often imputed to improve statistical power and to increase mapping resolution. The accuracy of standard imputation techniques strongly depends on the similarity of linkage disequilibrium (LD) patterns in the study and reference populations. Here we develop a novel approach for genotype imputation in low-recombination regions that relies on the coalescent and permits to explicitly account for population demographic factors. To test the new method, study and reference haplotypes were simulated and gene trees were inferred under the basic coalescent and also considering population growth and structure. The reference haplotypes that first coalesced with study haplotypes were used as templates for genotype imputation. Computer simulations were complemented with the analysis of real data. Genotype concordance rates were used to compare the accuracies of coalescent-based and standard (IMPUTE2) imputation. Simulations revealed that, in LD-blocks, imputation accuracy relying on the basic coalescent was higher and less variable than with IMPUTE2. Explicit consideration of population growth and structure, even if present, did not practically improve accuracy. The advantage of coalescent-based over standard imputation increased with the minor allele frequency and it decreased with population stratification. Results based on real data indicated that, even in low-recombination regions, further research is needed to incorporate recombination in coalescence inference, in particular for studies with genetically diverse and admixed individuals. To exploit the full potential of coalescent-based methods for the imputation of missing genotypes in genetic studies, further methodological research is needed to reduce computer time, to take into account recombination, and to implement these methods in user-friendly computer programs. Here we provide reproducible code which takes advantage of publicly available software to facilitate

  19. HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population.

    Directory of Open Access Journals (Sweden)

    Abdelhafidh Hajjej

    Full Text Available In view of its distinct geographical location and relatively small area, Tunisia witnessed the presence of many civilizations and ethnic groups throughout history, thereby questioning the origin of present-day Tunisian population. We investigated HLA class I and class II gene profiles in Tunisians, and compared this profile with those of Mediterranean and Sub-Sahara African populations. A total of 376 unrelated Tunisian individuals of both genders were genotyped for HLA class I (A, B and class II (DRB1, DQB1, using reverse dot-blot hybridization (PCR-SSO method. Statistical analysis was performed using Arlequin software. Phylogenetic trees were constructed by DISPAN software, and correspondence analysis was carried out by VISTA software. One hundred fifty-three HLA alleles were identified in the studied sample, which comprised 41, 50, 40 and 22 alleles at HLA-A,-B,-DRB1 and -DQB1 loci, respectively. The most frequent alleles were HLA-A*02:01 (16.76%, HLA-B*44:02/03 (17.82%, HLA-DRB1*07:01 (19.02%, and HLA-DQB1*03:01 (17.95%. Four-locus haplotype analysis identified HLA-A*02:01-B*50:01-DRB1*07:01-DQB1*02:02 (2.2% as the common haplotype in Tunisians. Compared to other nearby populations, Tunisians appear to be genetically related to Western Mediterranean population, in particular North Africans and Berbers. In conclusion, HLA genotype results indicate that Tunisians are related to present-day North Africans, Berbers and to Iberians, but not to Eastern Arabs (Palestinians, Jordanians and Lebanese. This suggests that the genetic contribution of Arab invasion of 7th-11th century A.D. had little impact of the North African gene pool.

  20. Automatic and Intentional Number Processing Both Rely on Intact Right Parietal Cortex: A Combined fMRI and Neuronavigated TMS Study

    Science.gov (United States)

    Cohen Kadosh, Roi; Bien, Nina; Sack, Alexander T.

    2012-01-01

    Practice and training usually lead to performance increase in a given task. In addition, a shift from intentional toward more automatic processing mechanisms is often observed. It is currently debated whether automatic and intentional processing is subserved by the same or by different mechanism(s), and whether the same or different regions in the brain are recruited. Previous correlational evidence provided by behavioral, neuroimaging, modeling, and neuropsychological studies addressing this question yielded conflicting results. Here we used transcranial magnetic stimulation (TMS) to compare the causal influence of disrupting either left or right parietal cortex during automatic and intentional numerical processing, as reflected by the size congruity effect and the numerical distance effect, respectively. We found a functional hemispheric asymmetry within parietal cortex with only the TMS-induced right parietal disruption impairing both automatic and intentional numerical processing. In contrast, disrupting the left parietal lobe with TMS, or applying sham stimulation, did not affect performance during automatic or intentional numerical processing. The current results provide causal evidence for the functional relevance of right, but not left, parietal cortex for intentional, and automatic numerical processing, implying that at least within the parietal cortices, automatic, and intentional numerical processing rely on the same underlying hemispheric lateralization. PMID:22347175

  1. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    Science.gov (United States)

    McCue, Marshall D; Guzman, R Marena; Passement, Celeste A; Davidowitz, Goggy

    2015-01-01

    Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths) on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae) were still relying extensively on lipids at the time of death, other species (crickets and moth larvae) allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  2. Moralized Rationality: Relying on Logic and Evidence in the Formation and Evaluation of Belief Can Be Seen as a Moral Issue

    Science.gov (United States)

    Skitka, Linda J.

    2016-01-01

    In the present article we demonstrate stable individual differences in the extent to which a reliance on logic and evidence in the formation and evaluation of beliefs is perceived as a moral virtue, and a reliance on less rational processes is perceived as a vice. We refer to this individual difference variable as moralized rationality. Eight studies are reported in which an instrument to measure individual differences in moralized rationality is validated. Results show that the Moralized Rationality Scale (MRS) is internally consistent, and captures something distinct from the personal importance people attach to being rational (Studies 1–3). Furthermore, the MRS has high test-retest reliability (Study 4), is conceptually distinct from frequently used measures of individual differences in moral values, and it is negatively related to common beliefs that are not supported by scientific evidence (Study 5). We further demonstrate that the MRS predicts morally laden reactions, such as a desire for punishment, of people who rely on irrational (vs. rational) ways of forming and evaluating beliefs (Studies 6 and 7). Finally, we show that the MRS uniquely predicts motivation to contribute to a charity that works to prevent the spread of irrational beliefs (Study 8). We conclude that (1) there are stable individual differences in the extent to which people moralize a reliance on rationality in the formation and evaluation of beliefs, (2) that these individual differences do not reduce to the personal importance attached to rationality, and (3) that individual differences in moralized rationality have important motivational and interpersonal consequences. PMID:27851777

  3. Moralized Rationality: Relying on Logic and Evidence in the Formation and Evaluation of Belief Can Be Seen as a Moral Issue.

    Directory of Open Access Journals (Sweden)

    Tomas Ståhl

    Full Text Available In the present article we demonstrate stable individual differences in the extent to which a reliance on logic and evidence in the formation and evaluation of beliefs is perceived as a moral virtue, and a reliance on less rational processes is perceived as a vice. We refer to this individual difference variable as moralized rationality. Eight studies are reported in which an instrument to measure individual differences in moralized rationality is validated. Results show that the Moralized Rationality Scale (MRS is internally consistent, and captures something distinct from the personal importance people attach to being rational (Studies 1-3. Furthermore, the MRS has high test-retest reliability (Study 4, is conceptually distinct from frequently used measures of individual differences in moral values, and it is negatively related to common beliefs that are not supported by scientific evidence (Study 5. We further demonstrate that the MRS predicts morally laden reactions, such as a desire for punishment, of people who rely on irrational (vs. rational ways of forming and evaluating beliefs (Studies 6 and 7. Finally, we show that the MRS uniquely predicts motivation to contribute to a charity that works to prevent the spread of irrational beliefs (Study 8. We conclude that (1 there are stable individual differences in the extent to which people moralize a reliance on rationality in the formation and evaluation of beliefs, (2 that these individual differences do not reduce to the personal importance attached to rationality, and (3 that individual differences in moralized rationality have important motivational and interpersonal consequences.

  4. How and When Do Insects Rely on Endogenous Protein and Lipid Resources during Lethal Bouts of Starvation? A New Application for 13C-Breath testing.

    Directory of Open Access Journals (Sweden)

    Marshall D McCue

    Full Text Available Most of our understanding about the physiology of fasting and starvation comes from studies of vertebrates; however, for ethical reasons, studies that monitor vertebrates through the lethal endpoint are scant. Insects are convenient models to characterize the comparative strategies used to cope with starvation because they have diverse life histories and have evolved under the omnipresent challenge of food limitation. Moreover, we can study the physiology of starvation through its natural endpoint. In this study we raised populations of five species of insects (adult grasshoppers, crickets, cockroaches, and larval beetles and moths on diets labeled with either 13C-palmitic acid or 13C-leucine to isotopically enrich the lipids or the proteins in their bodies, respectively. The insects were allowed to become postabsorptive and then starved. We periodically measured the δ13C of the exhaled breath to characterize how each species adjusted their reliance on endogenous lipids and proteins as energy sources. We found that starving insects employ a wide range of strategies for regulating lipid and protein oxidation. All of the insects except for the beetle larvae were capable of sharply reducing reliance on protein oxidation; however, this protein sparing strategy was usually unsustainable during the entire starvation period. All insects increased their reliance on lipid oxidation, but while some species (grasshoppers, cockroaches, and beetle larvae were still relying extensively on lipids at the time of death, other species (crickets and moth larvae allowed rates of lipid oxidation to return to prestarvation levels. Although lipids and proteins are critical metabolic fuels for both vertebrates and insects, insects apparently exhibit a much wider range of strategies for rationing these limited resources during starvation.

  5. Stepped MS(All) Relied Transition (SMART): An approach to rapidly determine optimal multiple reaction monitoring mass spectrometry parameters for small molecules.

    Science.gov (United States)

    Ye, Hui; Zhu, Lin; Wang, Lin; Liu, Huiying; Zhang, Jun; Wu, Mengqiu; Wang, Guangji; Hao, Haiping

    2016-02-11

    Multiple reaction monitoring (MRM) is a universal approach for quantitative analysis because of its high specificity and sensitivity. Nevertheless, optimization of MRM parameters remains as a time and labor-intensive task particularly in multiplexed quantitative analysis of small molecules in complex mixtures. In this study, we have developed an approach named Stepped MS(All) Relied Transition (SMART) to predict the optimal MRM parameters of small molecules. SMART requires firstly a rapid and high-throughput analysis of samples using a Stepped MS(All) technique (sMS(All)) on a Q-TOF, which consists of serial MS(All) events acquired from low CE to gradually stepped-up CE values in a cycle. The optimal CE values can then be determined by comparing the extracted ion chromatograms for the ion pairs of interest among serial scans. The SMART-predicted parameters were found to agree well with the parameters optimized on a triple quadrupole from the same vendor using a mixture of standards. The parameters optimized on a triple quadrupole from a different vendor was also employed for comparison, and found to be linearly correlated with the SMART-predicted parameters, suggesting the potential applications of the SMART approach among different instrumental platforms. This approach was further validated by applying to simultaneous quantification of 31 herbal components in the plasma of rats treated with a herbal prescription. Because the sMS(All) acquisition can be accomplished in a single run for multiple components independent of standards, the SMART approach are expected to find its wide application in the multiplexed quantitative analysis of complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells

    Science.gov (United States)

    Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

    2016-01-01

    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells. PMID:27028870

  7. Biological adhesion of the flatworm Macrostomum lignano relies on a duo-gland system and is mediated by a cell type-specific intermediate filament protein.

    Science.gov (United States)

    Lengerer, Birgit; Pjeta, Robert; Wunderer, Julia; Rodrigues, Marcelo; Arbore, Roberto; Schärer, Lukas; Berezikov, Eugene; Hess, Michael W; Pfaller, Kristian; Egger, Bernhard; Obwegeser, Sabrina; Salvenmoser, Willi; Ladurner, Peter

    2014-02-12

    Free-living flatworms, in both marine and freshwater environments, are able to adhere to and release from a substrate several times within a second. This reversible adhesion relies on adhesive organs comprised of three cell types: an adhesive gland cell, a releasing gland cell, and an anchor cell, which is a modified epidermal cell responsible for structural support. However, nothing is currently known about the molecules that are involved in this adhesion process. In this study we present the detailed morphology of the adhesive organs of the free-living marine flatworm Macrostomum lignano. About 130 adhesive organs are located in a horse-shoe-shaped arc along the ventral side of the tail plate. Each organ consists of exactly three cells, an adhesive gland cell, a releasing gland cell, and an anchor cell. The necks of the two gland cells penetrate the anchor cell through a common pore. Modified microvilli of the anchor cell form a collar surrounding the necks of the adhesive- and releasing glands, jointly forming the papilla, the outer visible part of the adhesive organs. Next, we identified an intermediate filament (IF) gene, macif1, which is expressed in the anchor cells. RNA interference mediated knock-down resulted in the first experimentally induced non-adhesion phenotype in any marine animal. Specifically, the absence of intermediate filaments in the anchor cells led to papillae with open tips, a reduction of the cytoskeleton network, a decline in hemidesmosomal connections, and to shortened microvilli containing less actin. Our findings reveal an elaborate biological adhesion system in a free-living flatworm, which permits impressively rapid temporary adhesion-release performance in the marine environment. We demonstrate that the structural integrity of the supportive cell, the anchor cell, is essential for this adhesion process: the knock-down of the anchor cell-specific intermediate filament gene resulted in the inability of the animals to adhere. The RNAi

  8. Ab-initio conformational epitope structure prediction using genetic algorithm and SVM for vaccine design.

    Science.gov (United States)

    Moghram, Basem Ameen; Nabil, Emad; Badr, Amr

    2018-01-01

    T-cell epitope structure identification is a significant challenging immunoinformatic problem within epitope-based vaccine design. Epitopes or antigenic peptides are a set of amino acids that bind with the Major Histocompatibility Complex (MHC) molecules. The aim of this process is presented by Antigen Presenting Cells to be inspected by T-cells. MHC-molecule-binding epitopes are responsible for triggering the immune response to antigens. The epitope's three-dimensional (3D) molecular structure (i.e., tertiary structure) reflects its proper function. Therefore, the identification of MHC class-II epitopes structure is a significant step towards epitope-based vaccine design and understanding of the immune system. In this paper, we propose a new technique using a Genetic Algorithm for Predicting the Epitope Structure (GAPES), to predict the structure of MHC class-II epitopes based on their sequence. The proposed Elitist-based genetic algorithm for predicting the epitope's tertiary structure is based on Ab-Initio Empirical Conformational Energy Program for Peptides (ECEPP) Force Field Model. The developed secondary structure prediction technique relies on Ramachandran Plot. We used two alignment algorithms: the ROSS alignment and TM-Score alignment. We applied four different alignment approaches to calculate the similarity scores of the dataset under test. We utilized the support vector machine (SVM) classifier as an evaluation of the prediction performance. The prediction accuracy and the Area Under Receiver Operating Characteristic (ROC) Curve (AUC) were calculated as measures of performance. The calculations are performed on twelve similarity-reduced datasets of the Immune Epitope Data Base (IEDB) and a large dataset of peptide-binding affinities to HLA-DRB1*0101. The results showed that GAPES was reliable and very accurate. We achieved an average prediction accuracy of 93.50% and an average AUC of 0.974 in the IEDB dataset. Also, we achieved an accuracy of 95

  9. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  10. AMBIGUITY OF LOCI DURING HLA-TYPING ON SSO TECHNOLOGY AND ATTEMPT TO RESOLVE THEM

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2010-01-01

    Full Text Available Sequence specific oligonucleotides typing was used to identify human leukocyte antigen (HLA-A, B, DRB1 alleles from 705 recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry and 155 of their number at locus HLA-C. 48 samples cannot be entered into the database because of ambiguities in the identification of allelic loci on HLA-class I – HLA-A, HLA-B. To resolution of ambiguity use reagents kits AlleleSEQR HLA Sequencing, which allowed to reveal the ambiguity of the locus HLA-A, 44% of cases, the loci HLA-B and HLA-C – 40% of cases. Application software HARPs Finder showed the possibility of resolution of all identified allelic ambiguities (with the exception of types of ambiguity – A*03/A*32 or A*74:13/A*32:04 and A*01/A*11 or A*36:04/A*11 with the addition of basic kits AlleleSEQR HLA Sequencing reagents kit Al- leleSEQR HARPs. 

  11. Summary of the 2010 AHPBA/SSO/SSAT Consensus Conference on HCC

    Directory of Open Access Journals (Sweden)

    Gitonga Munene

    2011-01-01

    Full Text Available Under the auspices of the American Hepato-Pancreato-Biliary Association, an expert consensus conference was convened in January 2010 on the multidisciplinary management of hepatocellular carcinoma. The goals of the conference were to address knowledge gaps in the optimal preparation of patients with HCC for operative therapy, best methods to control HCC while awaiting liver transplantation, and developing a multidisciplinary approach to these patients with implementation of novel systemic therapies.

  12. Sabiedriskās attiecības jauno reliģisko kustību praksē. Baznīcas "Jaunā paaudze" gadījuma analīze

    OpenAIRE

    Maļuha, Sandra

    2008-01-01

    Izstrādātā bakalaura darba nosaukums ir „Sabiedriskās attiecības jauno reliģisko kustību praksē: baznīcas „Jaunā paaudze” gadījuma analīze”. Darbā aplūkotā pētnieciskā problēma ir jauns, līdz šim maz pētīts fenomens - sabiedrisko attiecību mērķu realizācija jauno reliģisko kustību darbībā. Izvēlētais pētniecības objekts ir baznīca „Jaunā paaudze”, kura, pēc Tieslietu ministrijas Reliģisko lietu pārvaldes sniegtajiem datiem, šobrīd ir lielākā jaunā reliģiskā kustība Latvijā. Teorētiskā pama...

  13. Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy

    DEFF Research Database (Denmark)

    Kolte, Astrid Marie; Steffensen, Rudi; Christiansen, Ole Bjarne

    2016-01-01

    PROBLEM: Women with secondary recurrent pregnancy loss (RPL) after a boy have a reduced chance of live birth in the first pregnancy after referral if they carry HY-restricting HLA class II alleles, but long-term chance of live birth is unknown. METHODS OF STUDY: Live birth was compared for 540...... women with unexplained secondary RPL according to firstborn's sex and maternal carriage of HLA-DRB3*03:01, HLA-DQB1*05:01/02, HLA-DRB1*15, and HLA-DRB1*07. The groups were compared by Cox proportional hazard ratios. RESULTS: For women with at firstborn boy, maternal carriage of HY-restricting HLA class...... of HY-restricting HLA class II alleles decreases long-term chance of live birth in women with RPL after a boy....

  14. Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India.

    Science.gov (United States)

    Dutta, Mousumi; Dutta, Prafulla; Medhi, Subhash; Borkakoty, Biswajyoti; Biswas, Dipankar

    2018-05-01

    Human leucocyte antigen (HLA) represents one of the most highly polymorphic systems which plays a central role in the immune response. Genetic polymorphism of HLA in influenza A(H1N1)pdm09 infected population may be an important factor in disease progression and severity that needs further probing. In this study, a total of 110 Influenza like illness patients were recruited from the population of Assam, Northeast India, from which 35 cases infected by A(H1N1)pdm09 viruses and 35 controls were typed for HLA-A, B and DRB1 locus by PCR-SSP method. A total of seven alleles of HLA-A, 16 alleles of HLA-B, and 11 alleles of HLA-DRB1 locus were identified. The most common alleles within each locus in cases were HLA-A*11 (85.71%, P = 0.046), HLA-B*35 (25%, P = 0.0001), and HLA-DRB1*15 (49.35%,  P = 0.133) as compared to the controls, HLA-A*11 (40.82%), HLA-B*35 (0.00%), and HLA-DRB1*15 (67.53%). The frequency of HLA-A*11 and HLA-B*35 were significantly higher in cases as compared to the controls. In DRB1 locus, HLA-DRB1*10 was significantly higher in cases (20.78%, P = 0.005) than that of controls (0.00%). Whereas, HLA-DRB1*15 showed a higher frequency in controls than in cases. In addition, HLA-DRB3*01 (P = 0.053), DRB4*01 (P = 1.000), and DRB5*01(P = 0.591) were also identified along with HLA-DRB1 haplotype. From this preliminary study, it is suspected that there may be a role of HLA-A*11, HLA-B*35 and HLA-DRB1*10 in conferring susceptibility to influenza A(H1N1)pdm09 infection in the study population. A larger extended study on HLA polymorphism may explain the association between HLA and influenza A(H1N1)pdm09 infection and provide insights for HLA restricted peptide based vaccines. © 2018 Wiley Periodicals, Inc.

  15. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.

    Science.gov (United States)

    Wallentin, Lars; Yusuf, Salim; Ezekowitz, Michael D; Alings, Marco; Flather, Marcus; Franzosi, Maria Grazia; Pais, Prem; Dans, Antonio; Eikelboom, John; Oldgren, Jonas; Pogue, Janice; Reilly, Paul A; Yang, Sean; Connolly, Stuart J

    2010-09-18

    Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population. In the RE-LY trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18 024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all

  16. Does the Spatial Distribution of the Parasitic Mite Varroa jacobsoni Oud. (Mesostigmata: Varroidae) in Worker Brood of Honey Bee Apis Mellifera L. (Hymenoptera: Apidae) Rely on an Aggregative Process?

    Science.gov (United States)

    Salvy, M.; Capowiez, Y.; Le Conte, Y.; Salvy, M.; Clément, J.-L.

    Varroa jacobsoni is an ectoparasite of honey bees which reproduces in capped brood cells. Multi-infestation is frequently observed in worker brood and can be interpreted as an aggregative phenomenon. The aim of this study was to determine whether the distribution of V. jacobsoni in worker brood cells relies on a random or an aggregative process. We studied the distribution of Varroa females in capped worker brood at similar age by comparing, by a Monte Carlo test, the observed frequency distribution of mites per cell to simulated distributions based on a random process. A complementary approach, using the "nearest neighbor distances" (NND) with Monte Carlo tests, was investigated to study the spatial distribution (a) between mites in different cells and (b) between infested cells in brood. The observed distributions did not differ significantly from that expected by a random process, and we conclude that there is no aggregation during invasion of V. jacobsoni in worker brood.

  17. Spatial imagery relies on a sensory independent, though sensory sensitive, functional organization within the parietal cortex: a fMRI study of angle discrimination in sighted and congenitally blind individuals.

    Science.gov (United States)

    Bonino, Daniela; Ricciardi, Emiliano; Bernardi, Giulio; Sani, Lorenzo; Gentili, Claudio; Vecchi, Tomaso; Pietrini, Pietro

    2015-02-01

    Although vision offers distinctive information to space representation, individuals who lack vision since birth often show perceptual and representational skills comparable to those found in sighted individuals. However, congenitally blind individuals may result in impaired spatial analysis, when engaging in 'visual' spatial features (e.g., perspective or angle representation) or complex spatial mental abilities. In the present study, we measured behavioral and brain responses using functional magnetic resonance imaging in sighted and congenitally blind individuals during spatial imagery based on a modified version of the mental clock task (e.g., angle discrimination) and a simple recognition control condition, as conveyed across distinct sensory modalities: visual (sighted individuals only), tactile and auditory. Blind individuals were significantly less accurate during the auditory task, but comparable-to-sighted during the tactile task. As expected, both groups showed common neural activations in intraparietal and superior parietal regions across visual and non-visual spatial perception and imagery conditions, indicating the more abstract, sensory independent functional organization of these cortical areas, a property that we named supramodality. At the same time, however, comparisons in brain responses and functional connectivity patterns across experimental conditions demonstrated also a functional lateralization, in a way that correlated with the distinct behavioral performance in blind and sighted individuals. Specifically, blind individuals relied more on right parietal regions, mainly in the tactile and less in the auditory spatial processing. In sighted, spatial representation across modalities relied more on left parietal regions. In conclusions, intraparietal and superior parietal regions subserve supramodal spatial representations in sighted and congenitally blind individuals. Differences in their recruitment across non-visual spatial processing in

  18. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    Directory of Open Access Journals (Sweden)

    Emilie Sundqvist

    2014-04-01

    Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and

  19. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T.; Olsen, Inge C.; Andreassen, Bettina K.; Viken, Marte K.; Jiang, Xia; Alfredsson, Lars; Kallberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I. W.; Martin, Javier; Teruel, Maria; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K.; Lie, Benedicte A.

    Objective Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  20. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T; Olsen, Inge C; Andreassen, Bettina K; Viken, Marte K; Jiang, Xia; Alfredsson, Lars; Källberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I W; Martin, Javier; Teruel, María; Gonzalez-Gay, Miguel A; Rodríguez-Rodríguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K; Lie, Benedicte A

    OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  1. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits.

  2. A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study

    Czech Academy of Sciences Publication Activity Database

    Vernerová, L.; Špoutil, František; Vlček, M.; Kršková, K.; Penesová, A.; Mesková, M.; Marko, A.; Raslová, K.; Vohnout, B.; Rovenský, J.; Killinger, Z.; Jochmanová, I.; Lazurová, I.; Steiner, G.; Smolen, J.; Imrich, R.

    2016-01-01

    Roč. 11, č. 4 (2016), č. článku e0153316. E-ISSN 1932-6203 Institutional support: RVO:68378050 Keywords : genome-wide association * hla-drb1 shared epitope * gene-environment interactions * citrullinated proteins * susceptibility genes * risk loci * cohort * antibodies * progression * population Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  3. Private-sector caesarean sections in perspective

    African Journals Online (AJOL)

    2005-02-28

    Feb 28, 2005 ... with HLA-DRB1'010l and abrogated by low CD4 T-cell counts. ... Benn PD, Mercey DE, Scott G, Williams IG. ... patient's right to choose a health intervention that may not be .... schemes environment is that of CS rates in the emerging .... Wax JR, Cartin A, Pinette MG, Blackstone J. Patient choice cesarean: ...

  4. [Correlation between HLA-DB1 genes and susceptibility to echinococcosis in Tibetan population in Tibetan Plateau].

    Science.gov (United States)

    Shu-Feng, Gao; Xiu-Min, Han; Xue-Fei, Zhang; Yong-Shun, Wang; Wei, Wang; Ya-Min, Guo; Yong-Shou, Li

    2017-10-23

    To determine the susceptibility genes and resistance genes in HLA-DRB1 alleles in Tibetan patients with cystic and alveolar hydatid diseases, so as to provide the references for the research of the genetic characteristics and infection mechanism of Tibetan hydatid diseases. The case control method was applied. The Tibetan patients with cystic and alveolar hydatid diseases (63 and 73 cases respectively) in Yushu and Guoluo Tibetan Autonomous Prefecture, and unrelated healthy people (60 cases) in this area were selected as the study subjects. The polymerase chain reaction-sequence based typing (PCR-SBT) technique was applied for genotyping of HLA-DRB1, and the comparison of the gene frequency. The frequency of HLA-DRB1*04 in the alveolar/cystic echinococcosis group was lower than that in the control group ( χ 2 = 4.71, 4.31, both P < 0.05). HLA-DRB1*04 genotypes may be associated with the resistance of cystic and alveolar echinococcosis and its resistance genes.

  5. Comparison of allele frequency for HLA-DR and HLA-DQ between patients with ECC and caries-free children

    Directory of Open Access Journals (Sweden)

    Bagherian A

    2008-03-01

    Full Text Available Background: Early childhood caries (ECC is one of the most common diseases of childhood. The etiology of ECC is multifactorial and both genetic and environmental factors play important roles in the pathogenesis of the disease. Genetic variations in the hosts may contribute to changes in the risk for dental caries. Genetic factors such as human leukocyte antigen (HLA have recently been suggested as a predisposing factor. Aim: The aim of this study was to look for an association between HLA-DRB1 and HLA-DQB1 with ECC for developing new strategies for the diagnosis as well as the prevention of the disease. Design: In this study, we extracted the genomic DNAs from whole blood samples of 44 patients with ECC and 35 caries-free children by the salting-out method. We amplified the genomic DNA by PCR-SSP and then HLA-typing was performed for all alleles. Results: The results revealed a significant increase in the frequency of HLA-DRB1FNx0104 in the patient group (P = 0.019. The odds ratio for this allele was detected to be 10. The frequency of HLA-DQB1 alleles was not significantly different between the two groups. Conclusion: The above results suggest that HLA-DRB1FNx0104 is associated with the susceptibility to ECC. Thus HLA-DRB1FNx0104 detection as a molecular marker for early diagnosis of ECC may be recommended.

  6. DNA polymorphism of HLA class II genes in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Cowland, J B; Andersen, V; Halberg, P

    1994-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3...

  7. DNA polymorphism of HLA class II genes in pauciarticular juvenile rheumatoid arthritis

    DEFF Research Database (Denmark)

    Morling, N; Friis, J; Fugger, L

    1991-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DPB in 54 patients with pauciarticular juvenile rheumatoid arthritis (PJRA) and in healthy Danes. The frequencies of DNA fragments a...

  8. Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy

    NARCIS (Netherlands)

    Rider, L. G.; Gurley, R. C.; Pandey, J. P.; Garcia de la Torre, I.; Kalovidouris, A. E.; O'Hanlon, T. P.; Love, L. A.; Hennekam, R. C.; Baumbach, L. L.; Neville, H. E.; Garcia, C. A.; Klingman, J.; Gibbs, M.; Weisman, M. H.; Targoff, I. N.; Miller, F. W.

    1998-01-01

    OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared

  9. A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study

    Czech Academy of Sciences Publication Activity Database

    Vernerová, L.; Špoutil, František; Vlček, M.; Kršková, K.; Penesová, A.; Mesková, M.; Marko, A.; Raslová, K.; Vohnout, B.; Rovenský, J.; Killinger, Z.; Jochmanová, I.; Lazurová, I.; Steiner, G.; Smolen, J.; Imrich, R.

    2016-01-01

    Roč. 11, č. 4 (2016), e0153316 E-ISSN 1932-6203 Institutional support: RVO:68378041 Keywords : genome-wide association * HLA-DRB1 shared epitope * gene-environment interactions Subject RIV: FP - Other Medical Disciplines Impact factor: 2.806, year: 2016

  10. Diagnosis and classification of Goodpasture's disease (anti-GBM).

    Science.gov (United States)

    Hellmark, Thomas; Segelmark, Mårten

    2014-01-01

    Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. An Investigation on the impact of using problem-based trainings in the in-service courses on the teachers' performance and capabilities, by relying on the elementary sixth grade mathematics book (case study: the city of Ahvaz

    Directory of Open Access Journals (Sweden)

    Pari Cheraq

    2017-02-01

    Full Text Available Changes in the administrative structure of the education system and the need to coordinate with the world of science and technology and hence, the need to update the general and technical information and knowledge, have doubled the importance and necessity of holding the new and efficient in-service trainings for the teachers. In this study, the attempt was taken to examine and analyze the impact of using problem-based trainings during the in-service courses on the teachers' performance and capabilities, by relying on the mathematics book of the sixth grade elementary level (case study: the city of Ahvaz. To do so, using a quasi-experimental study, 37 teachers of the sixth grade were selected from the elementary schools of Ahvaz city. For the in-service training courses on the teaching of mathematics, the problem-based learning method was used. After conducting the problem-based teaching method and the traditional method of teaching, through using the test and the standard questionnaire, the data about the teaching practice and the capabilities of the teachers were collected. Using t-test for the paired and independent samples, it was demonstrated that the problem-based in-service trainings, enhance the teachers' capabilities and performance regarding the problem-solving skills.

  12. Prevalence of multiple sclerosis in Verona, Italy: an epidemiological and genetic study.

    Science.gov (United States)

    Gajofatto, A; Stefani, A; Turatti, M; Bianchi, M R; Lira, M G; Moretto, G; Salviati, A; Benedetti, M D

    2013-04-01

    Recent multiple sclerosis (MS) prevalence studies classify Italy as a high-risk area without intra-regional latitude effect. To determine MS prevalence in Verona, Italy, and frequency of myelin oligodendrocyte glycoprotein (MOG) gene G511C polymorphism and HLA-DRB1*15 locus in a sample of cases and healthy controls. The study area population on the prevalence date (31 December 2001) was 253208 (133508 women, 119700 men). Multiple case sources were examined. Patients fulfilling McDonald's criteria (2001) were included. Crude, age- and sex-specific prevalence rates were computed. MOG G511C polymorphism and HLA-DRB1*15 were determined by standard methods. We identified 270 cases of MS yielding a crude prevalence rate of 106.6/100000 (95% CI: 94-120). Prevalence was higher in women (140.8/100000) than in men (68.5/100000). The age-adjusted prevalence rate standardized to the European population was 96.0/100000. MOG G511C polymorphism did not differ between cases and controls. HLA-DRB1*15 frequency was 58/155 (37%) in cases and 24/157 (15%) in controls (P<0.001). There was no HLA-DRB1*15 influence on susceptibility to other autoimmune disorders. The high MS prevalence in Verona confirms Italy as a high-risk area with a homogenous distribution across the country. HLA-DRB1*15 is a relevant MS susceptibility locus in the Italian population, possibly with little influence on the occurrence of concomitant autoimmune disorders. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  13. A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Judith Field

    2010-10-01

    Full Text Available We conducted an association study across the human leukocyte antigen (HLA complex to identify loci associated with multiple sclerosis (MS. Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P ≤ 4 x 10(-6. All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P ≤ 0.001 and were highly significant in the combined dataset (P ≤ 6 x 10(-8. The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set P = 9 x 10(-9, replication set P = 7 x 10(-4, combined P = 2 x 10(-10. HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

  14. Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage.

    Science.gov (United States)

    Delbos, Florent; Bertrand, Gérald; Croisille, Laure; Ansart-Pirenne, Hélène; Bierling, Philippe; Kaplan, Cécile

    2016-01-01

    In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most frequently caused by maternal alloimmunization against the human platelet antigen HPA-1a. The most serious complication of severe FNAIT is intracranial hemorrhage (ICH). ICH mainly occurs in utero; therefore, there is a need to identify noninvasive predictive factors of ICH to facilitate early identification of this condition and to determine response to maternal therapy. We studied gynecologic and immunogenetic variables of severe cases of anti-HPA-1a FNAIT within three groups: Group I, FNAIT without ICH; Group II, FNAIT with ICH; and Group III, suspected FNAIT cases without detectable maternal anti-HPA-1a alloantibodies. ICH was associated with a poor outcome because it led to death in 59% of cases. Multigravida (two or more pregnancies) was overrepresented in Group II, consistent with the high concentrations of maternal HPA-1a alloantibody and the frequent detection of a strong newborn-specific HLA class I antibody response at delivery. The proportion of HLA-DRB4*01:01P (*01:01 or *01:03) women was similar in Groups I and II, but this allele was overrepresented in Group III, in which FNAIT was less severe than in the other two groups. Finally, antenatal intravenous immunoglobulin therapy tended to be more effective in HLA-DRB3*01:01(+)/HLA-DRB4*01:01P(+) women than for HLA-DRB3*01:01(+)/HLA-DRB4*01:01P(-) women. The number of gestations is a predictive factor of ICH in anti-HPA-1a-alloimmunized women. Maternal immunogenetic variables should be investigated in the context of maternal immunization and may predict response to maternal therapy in subsequent pregnancies. © 2015 AABB.

  15. Ege bölgesi standart süreli yıllık maksimum yağışları için en uygun dağılımlar

    Directory of Open Access Journals (Sweden)

    Halil Karahan

    2013-03-01

    Full Text Available Su kaynaklarının temel girdisi olan yağışların; miktarı, süresi, şiddeti, alansal ve zamansal değişimi v.b. özelliklerinin bilinmesi; su kaynakları, tarım, kentleşme, drenaj, taşkın kontrolü ve ulaşım gibi farklı sektörlere ait planlama, tasarım, inşaat ve işletme çalışmaları için gereklidir. Belirtilen faaliyetlerin gerçekleştirilebilmesi için; mevcut gözlemlere dayalı, güvenilir ve gerçekçi tahminlerin yapılması gerekir. Güvenilir tahmin yapabilmenin ilk aşaması ise mevcut gözlemlerin güvenirliğinin test edilmesidir. Bu çalışmada; DMİ Genel Müdürlüğü tarafından işletilen Ege Bölgesi il ve ilçe merkezlerinde yer alan meteoroloji istasyonlarında (1929-2005 yıllarında ölçülen standart süreli maksimum yağış değerlerinin hangi dağılıma uyduklarını belirlemek için; Kolmogorov-Smirnov, Anderson-Darling ve Ki-Kare dağılım uygunluk testleri uygulanmıştır. Anderson-Darling testine göre gözlemlerin tümüne yakını GEV dağılımına uyum gösterirken, Kolmogorov-Smirnov ve Ki-Kare testlerine göre kısa, orta ve uzun süreli yağış gözlemleri için genellikle GEV, Gamma ve Log-Normal dağılımın uygun olduğu görülmüştür. Seçilen olasılık dağılımının parametrelerini belirlemek için farklı dağılımlara göre maksimum olabilirlik (LN2, LN3, EXP2, Gamma3, olasılık-ağırlıklı momentler (LP3,Gamma2, L-momentler (GEV ve en küçük kareler (Weibull2 yöntemleri kullanılmıştır.

  16. Haber Üretiminde Göreli Özerklik Problemi: Bir Saha Araştırması / The Relative Autonomy Problem in Newsmaking Process: A Field Research

    Directory of Open Access Journals (Sweden)

    Deniz Tansel İLİC

    2014-09-01

    Full Text Available Kültürel simgelerin üretim sürecinde görev yapan enformasyon işçilerinin özerkliği, sosyal bilimler açısından önemli bir tartışma konusudur. Üretim sürecini sadece sahiplik üzerinden değerlendiren yaklaşımlar, mülkiyet ilişkilerinin, simge üreticisinin özerklik alanını tamamen kısıtlayacağını savunurlar. Yine de, zihinsel emekleri ile çalışan simge üreticilerinin, belli oranda özerkliğe sahip olduğu iddiası sınamaya değerdir. Bu çalışmada, David Hesmondhalgh ve Mike Wayne’deki göreli özerklik vurgusundan yola çıkarak, Türkiye’de anaakım televizyon haberciliğinde bir saha araştırması yapılmıştır. Fox TV, TGRT Haber ve Kanal D’de gerçekleştirilen katılımlı gözlemlerle, birer simge üreticisi olan habercilerin, hangi oranda özerk oldukları saptanmaya çalışılmıştır. / The autonomy of information workers who work in the production process of cultural symbols is an important issue for social sciences. The approaches that evaluate the production process only in the context of ownership claim that these relationships will restrain the autonomy field of the symbol producer. Still the suggestion that symbol producers who work with their mental labours have a certain amount of autonomy is worth testing. In this study a field research is conducted in mainstream broadcasting in Turkey by using the relative autonomy emphasis in David Hesmondhalgh and Mike Wayne as a starting point. In the participant observation that is conducted in Fox TV, TGRT Haber and Kanal D Televisions it is tried to determine at what level the journalists as symbol producers are autonomous.

  17. Early LC3 lipidation induced by d-limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells.

    Science.gov (United States)

    Berliocchi, Laura; Chiappini, Carlotta; Adornetto, Annagrazia; Gentile, Debora; Cerri, Silvia; Russo, Rossella; Bagetta, Giacinto; Corasaniti, Maria Tiziana

    2018-02-01

    d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies. Autophagy is an intracellular catabolic process serving as both an adaptive metabolic response and a quality control mechanism. Because autophagy defects have been linked to a wide range of human pathologies, including neurodegeneration and cancer, there is a need for new pharmacological tools to control deregulated autophagy. To better understand the effects of d-limonene on autophagy, to identify the molecular mechanisms through which this monoterpene rapidly triggers LC3 lipidation and to evaluate the role for autophagy in long-term effects of d-limonene. Human SH-SY5Y neuroblastoma, HepG2 hepatocellular carcinoma and MCF7 breast cancer cells were used. Endogenous LC3-II levels were evaluated by western blotting. Autophagic flux assay was performed using bafilomycin A1 and chloroquine. Intracellular distribution of LC3 protein was studied by confocal microscopy analysis of LC3B-GFP transduced cells. Expression of lysosomal-membrane protein LAMP-1 was assessed by immunofluorescence analysis. Phosphorylated levels of downstream substrates of mTOR kinase (p70S6 kinase, 4E-BP1, and ULK1) and ERK were analyzed by western blotting. Production of reactive oxygen species (ROS) was assessed by live confocal microscopy of cells loaded with CellROX ® Green Reagent. Clonogenic assay was used to evaluate the ability of treated cells to proliferate and form colonies. LC3 lipidation promoted by d-limonene correlates with autophagosome formation and stimulation of basal autophagy. LC3 lipidation does not rely on inhibition of mTOR kinase, which instead appears to be transiently activated. In addition, d-limonene rapidly activates ERK and

  18. Comparing HLA shared epitopes in French Caucasian patients with scleroderma.

    Directory of Open Access Journals (Sweden)

    Doua F Azzouz

    Full Text Available Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc, none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67FLEDR(71, shared by HLA-DRB susceptibility alleles, or (71TRAELDT(77, shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient's clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ(2 = 28.4, p<10-6 and with anti-topoisomerase antibody (ATA production (χ(2 = 43.9, p<10-9 whereas TRAELDT association is weaker in both subgroups (χ(2 = 7.2, p = 0.027 and χ(2 = 14.6, p = 0.0007 respectively. Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes.In French Caucasian patients with SSc, FLEDR is the main presenting motif influencing ATA production in dcSSc. These results open a new field of potential therapeutic applications to interact with the FLEDR peptide binding groove and prevent ATA production, a hallmark of severity in SSc.

  19. Evaluation of the Use of Periodicals Collection of the Higher Education Council Documentation and Online Search Center: Arts and Humanities Periodicals YÖK Dokümantasyon ve Uluslararası Bilgi Tarama Merkezi Koleksiyonundaki Sanat ve Beşeri Bilimler Konulu Süreli Yayınların Kullanım Değerlendirmesi

    Directory of Open Access Journals (Sweden)

    Elçin Özbudak

    1995-06-01

    Full Text Available Evaluation of the use perodicals collections in libraries is important as perodicals report the results of the latest scientific research and they are usually more expensive than other types of library materials. In this study we evaluate the use of Arts and Humanities periodicals in the collection of the Higher Education Council Documentation Center. Although the use of Arts and Humanities periodicals was found to be lower than, say, Biomedical periodicals collection, the number of journal titles in Arts and Humanities appears to be quite satisfactory. Some suggestions are made so as to increase the use of Arts and Humanities periodicals collection. Bilimsel araştırmalar için en güncel bilgileri veren ve maliyeti diğer materyallere göre daha fazla olan süreli yayınların ne oranda kullanıldığının araştırılması, koleksiyon değerlendirmesi açısından önemlidir. Bu amaçla, Yükseköğretim Kurulu Dokümantasyon ve Uluslararası Bilgi Tarama Merkezi süreli yayınlar koleksiyonunun genel bir değerlendirmesi yapılarak "Sanat ve Beşeri Bilimler" konulu süreli yayınların kullanımları incelenmiş, Yükseköğretim Kurulu Dokümantasyon ve Uluslararası Bilgi Tarama Merkezi 'nde önemli ve büyük bir süreli yayınlar koleksiyonu bulunduğu, "Sanat ve Beşeri Bilimler" konulu süreli yayınların da yeterli olduğu sonuçları çıkartılmıştır. "Sanat ve Beşeri Bilimler" konulu süreli yayınların kullanımlarının nispeten düşük oluşu, bu alanda çalışan araştırmacıların süreli yayınlara yeterince ilgi göstermemelerine bağlanarak, kullanımı artırmak için öneriler getirilmiştir.

  20. Intermediation in Foreign Trade: When do Exporters Rely on Intermediaries?

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Trabold, H.; Trübswetter, P.

    2005-01-01

    The paper explores the question of why trade intermediaries (TIs) are frequently used as agents for exports to some countries but not to others. First, we adapt a standard intra-industry trade model with variable export costs (e.g. transport) and fixed export costs (e.g. market access) to include...... a TI that is able to pool market access cost. This framework suggests explanatory factors for the TI share in a country's exports, which are largely in line with the literature. Second, we test these explanatory factors with a new data set based on French customs information. The paper finds that: (i......) higher market access costs increase the TI share, (ii) smaller export markets feature a larger TI share, (iii) network effects are important determinants of trade intermediation....

  1. Intermediation in Foreign Trade: When do Exporters Rely on Intermediaries?

    DEFF Research Database (Denmark)

    Schröder, Philipp; Trabold, Harald; Trübswetter, Parvati

    2003-01-01

    The paper explores theoretically and empirically why trade intermediaries (TIs) are frequently used as agents for exports to some countries but not to others. We adapt a standard intra-industry trade model with variable export costs (e.g. transport) and fixed export costs (e.g. market access......) to include a TI that is able to pool market access cost. From this framework explanatory factors for the TI share in a country's exports are derived and subsequently tested with a new data set based on French customs information. The paper finds that: (i) higher market access costs increase the TI share, (ii......) smaller export markets feature a larger TI share, (iii) the TI share is independent from variable (distance-dependent) export costs....

  2. Towards Concept Understanding relying on Conceptualisation in Constructivist Learning

    DEFF Research Database (Denmark)

    Badie, Farshad

    2017-01-01

    and understandings over their mental structures in the framework of constructivism, and I will clarify my logical [and semantic] conceptions of humans’ concept understandings. This research focuses on philosophy of education and on logics of human learning. It connects with the topics ‘Cognition in Education......, through this constructivism to a pedagogical theory of learning. I will mainly focus on conceptual and epistemological analysis of humans’ conceptualisations based on their own mental objects (schemata). Subsequently, I will propose an analytical specification of humans’ conceptualisations...

  3. A Formal Semantics for Concept Understanding relying on Description Logics

    DEFF Research Database (Denmark)

    Badie, Farshad

    2017-01-01

    logical assumptions whose discovery may lead us to a better understanding of ‘concept understanding’. The Structure of Observed Learning Outcomes (SOLO) model as an appropriate model of increasing complexity of humans’ understanding has supported the formal analysis.......In this research, Description Logics (DLs) will be employed for logical description, logical characterisation, logical modelling and ontological description of concept understanding in terminological systems. It’s strongly believed that using a formal descriptive logic could support us in revealing...

  4. Uganda's beef industry has for long relied on indigenous cattle ...

    African Journals Online (AJOL)

    Animal

    growing. The Ministry of Agriculture Animal Industry and Fisheries estimated the exotic/crossbred cattle population at 1.3 million, .... Carcass components. Slaughter weight 248.7 250.2 255.0. 3.8. 220.2c. 257.1b. 276.5a. 4.0 ns. ***. Hot carcass weight. 126.7 129.3 130.8. 2.4. 109.6c. 132.3b. 145.0a. 2.5 ns. ***. Hot carcass ...

  5. A Formal Semantics for Concept Understanding relying on Description Logics

    DEFF Research Database (Denmark)

    Badie, Farshad

    2017-01-01

    In this research, Description Logics (DLs) will be employed for logical description, logical characterisation, logical modelling and ontological description of concept understanding in terminological systems. It’s strongly believed that using a formal descriptive logic could support us in reveali...... logical assumptions whose discovery may lead us to a better understanding of ‘concept understanding’. The Structure of Observed Learning Outcomes (SOLO) model as an appropriate model of increasing complexity of humans’ understanding has supported the formal analysis....

  6. On liberation of communities which relies on nuclear power

    International Nuclear Information System (INIS)

    Park, Seung-Joon

    2013-01-01

    Just after the Nuclear Regulation Authority pointed out possible active faults for fracture zones just under the Tsuruga nuclear power station, local government of reactor site criticized this view was mere judgement of small experts group after its short-term field survey and evaluation meeting without enough discussion with nuclear operators. Behavior of local government, which should insist assurance of residents safety at first, seemed inscrutable and the industrial and financial structure of communities dependent on nuclear power should be clarified. Accident affected costs of nuclear power station estimated in the past were far beyond several trillion yen but local residents of reactor site used to believe accident risk might be negligible because of quite low accident probability estimated by probabilistic safety analysis. Economy of local government of reactor site was dependent on nuclear power. Economic benefits consisted of tax or subsidy income of local governments (financial aspect) and limited employment or grants of residents (economical aspect). Depreciation of relevant nuclear power station varied financial dependency of local government respectively, which could be compensated by local tax subsidy after nuclear power was abolished. Local industry dependent on nuclear power was mostly subcontracted building work or related service industry. Nuclear power phaseout could bring about new employment of residents at reactor site with decommissioning works and introduction of gas-fired thermal power or production center for renewable energy. (T. Tanaka)

  7. CASE STUDY: The Philippines — Progress relies on sound ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-12-17

    Dec 17, 2010 ... Today, Pasay suffers from overcrowding, unemployment, and ... Ensure environmental sustainability; Develop a global partnership for development. ... in partnership with the business sector, decided to organize job fairs in ...

  8. Mosquitoes rely on their gut microbiota for development

    Science.gov (United States)

    Coon, Kerri L.; Vogel, Kevin J.; Brown, Mark R.; Strand, Michael R.

    2014-01-01

    Field studies indicate adult mosquitoes (Culicidae) host low diversity communities of bacteria that vary greatly among individuals and species. In contrast, it remains unclear how adult mosquitoes acquire their microbiome, what influences community structure, and whether the microbiome is important for survival. Here we used pyrosequencing of 16S rRNA to characterize the bacterial communities of three mosquito species reared under identical conditions. Two of these species, Aedes aegypti and Anopheles gambiae, are anautogenous and must blood feed to produce eggs, while one, Georgecraigius atropalpus, is autogenous and produces eggs without blood feeding. Each mosquito species contained a low diversity community comprised primarily of aerobic bacteria acquired primarily from the aquatic habitat in which larvae developed. Our results suggested the communities in Ae. aegypti and An. gambiae larvae share more similarities with one another than with Ge. atropalpus. Studies with Ae. aegypti also strongly suggested that adults transstadially acquired several members of the larval bacterial community, but only four genera of bacteria present in blood fed females were detected on eggs. Functional assays showed that axenic larvae of each species failed to develop beyond the first instar. Experiments with Ae. aegypti indicated several members of the microbial community and Escherichia coli successfully colonized axenic larvae and rescued development. Overall, our results provide new insights about the acquisition and structure of bacterial communities in mosquitoes. They also indicate three mosquito species spanning the breadth of the Culicidae depend on their gut microbiome for development. PMID:24766707

  9. Organization of Circadian Behavior Relies on Glycinergic Transmission.

    Science.gov (United States)

    Frenkel, Lia; Muraro, Nara I; Beltrán González, Andrea N; Marcora, María S; Bernabó, Guillermo; Hermann-Luibl, Christiane; Romero, Juan I; Helfrich-Förster, Charlotte; Castaño, Eduardo M; Marino-Busjle, Cristina; Calvo, Daniel J; Ceriani, M Fernanda

    2017-04-04

    The small ventral lateral neurons (sLNvs) constitute a central circadian pacemaker in the Drosophila brain. They organize daily locomotor activity, partly through the release of the neuropeptide pigment-dispersing factor (PDF), coordinating the action of the remaining clusters required for network synchronization. Despite extensive efforts, the basic principles underlying communication among circadian clusters remain obscure. We identified classical neurotransmitters released by sLNvs through disruption of specific transporters. Adult-specific RNAi-mediated downregulation of the glycine transporter or impairment of glycine synthesis in LNv neurons increased period length by nearly an hour without affecting rhythmicity of locomotor activity. Electrophysiological recordings showed that glycine reduces spiking frequency in circadian neurons. Interestingly, downregulation of glycine receptor subunits in specific sLNv targets impaired rhythmicity, revealing involvement of glycine in information processing within the network. These data identify glycinergic inhibition of specific targets as a cue that contributes to the synchronization of the circadian network. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Radiological services pact relies on teamwork and experience [dose management

    International Nuclear Information System (INIS)

    Cruden, D.S.

    1988-01-01

    Virginia Power has entered into a radiological service agreement with Westinghouse. The contract commits Westinghouse to work in partnership with Virginia Power to improve performance in the areas of radiological protection, decontamination, ALARA, and radioactive waste management. It is expected that the agreement will solve the problems caused by the shortage of qualified contractor personnel during scheduled outages. (U.K.)

  11. Supercontinuum generation in silicon waveguides relying on wave-breaking.

    Science.gov (United States)

    Castelló-Lurbe, David; Silvestre, Enrique

    2015-10-05

    Four-wave-mixing processes enabled during optical wave-breaking (OWB) are exploited in this paper for supercontinuum generation. Unlike conventional approaches based on OWB, phase-matching is achieved here for these nonlinear interactions, and, consequently, new frequency production becomes more efficient. We take advantage of this kind of pulse propagation to obtain numerically a coherent octave-spanning mid-infrared supercontinuum generation in a silicon waveguide pumping at telecom wavelengths in the normal dispersion regime. This scheme shows a feasible path to overcome limits imposed by two-photon absorption on spectral broadening in silicon waveguides.

  12. Fast uncertainty reduction strategies relying on Gaussian process models

    International Nuclear Information System (INIS)

    Chevalier, Clement

    2013-01-01

    This work deals with sequential and batch-sequential evaluation strategies of real-valued functions under limited evaluation budget, using Gaussian process models. Optimal Stepwise Uncertainty Reduction (SUR) strategies are investigated for two different problems, motivated by real test cases in nuclear safety. First we consider the problem of identifying the excursion set above a given threshold T of a real-valued function f. Then we study the question of finding the set of 'safe controlled configurations', i.e. the set of controlled inputs where the function remains below T, whatever the value of some others non-controlled inputs. New SUR strategies are presented, together with efficient procedures and formulas to compute and use them in real world applications. The use of fast formulas to recalculate quickly the posterior mean or covariance function of a Gaussian process (referred to as the 'kriging update formulas') does not only provide substantial computational savings. It is also one of the key tools to derive closed form formulas enabling a practical use of computationally-intensive sampling strategies. A contribution in batch-sequential optimization (with the multi-points Expected Improvement) is also presented. (author)

  13. Pantomimes are special gestures which rely on working memory.

    Science.gov (United States)

    Bartolo, A; Cubelli, R; Della Sala, S; Drei, S

    2003-12-01

    The case of a patient is reported who presented consistently with overt deficits in producing pantomimes in the absence of any other deficits in producing meaningful gestures. This pattern of spared and impaired abilities is difficult to reconcile with the current layout of cognitive models for praxis. This patient also showed clear impairment in a dual-task paradigm, a test taxing the co-ordination aspect of working memory, though performed normally in a series of other neuropsychological measures assessing language, visuo-spatial functions, reasoning function, and executive function. A specific working memory impairment associated with a deficit of pantomiming in the absence of any other disorders in the production of meaningful gestures suggested a way to modify the model to account for the data. Pantomimes are a particular category of gestures, meaningful, yet novel. We posit that by their very nature they call for the intervention of a mechanism to integrate and synthesise perceptual inputs together with information made available from the action semantics (knowledge about objects and functions) and the output lexicon (stored procedural programmes). This processing stage conceived as a temporary workspace where gesture information is actively manipulated, would generate new motor programmes to carry out pantomimes. The model of gesture production is refined to include this workspace.

  14. Detection of pressure tube leaks relying on moisture beetles only

    International Nuclear Information System (INIS)

    Kenchington, J.M.; Choi, A.; Jin, Y.

    2004-01-01

    A major decision was made for Pickering NGS A Annulus Gas System (ACS) that detection of a pressure tube (PT) leak should be achieved by using only moisture beetles and that dew point monitors would provide 'early warning' without status to shut down the reactor. Experience with Unit 3 has shown that dew point monitoring of pressure tube leaks was particularly subject to gas leaks and surface adsorption effects. Unit 4 was the first one to be converted during the full scale pressure tube replacement programme. Because of the fundamental change in design philosophy, moisture injection tests were carried out during commissioning to demonstrate that performance matched design. In particular it was necessary to show that leak before break (LBB) would be achieved if a leak occurred in the limiting string. Units 1 and 3 have since been converted. No decision has been taken to convert Pickering B units as gas leaks are small and no significant adsorption effects are anticipated. Hence dew point monitoring will not be impaired. (author)

  15. Unlocking good design does not rely on designers alone

    DEFF Research Database (Denmark)

    Rodil, Kasper; Eskildsen, Søren; Morrison, Ann

    This article describes on-going research in the design of sustainable systems to support transfer of indigenous knowledge between rural elders and city living youths in Namibia. Specifically we here address the importance of co-design and highlight some of our findings through experiences gathere...

  16. Hepatitis C virus relies on lipoproteins for its life cycle.

    Science.gov (United States)

    Grassi, Germana; Di Caprio, Giorgia; Fimia, Gian Maria; Ippolito, Giuseppe; Tripodi, Marco; Alonzi, Tonino

    2016-02-14

    Hepatitis C virus (HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production.

  17. Why cryptography should not rely on physical attack complexity

    CERN Document Server

    Krämer, Juliane

    2015-01-01

    This book presents two practical physical attacks. It shows how attackers can reveal the secret key of symmetric as well as asymmetric cryptographic algorithms based on these attacks, and presents countermeasures on the software and the hardware level that can help to prevent them in the future. Though their theory has been known for several years now, since neither attack has yet been successfully implemented in practice, they have generally not been considered a serious threat. In short, their physical attack complexity has been overestimated and the implied security threat has been underestimated. First, the book introduces the photonic side channel, which offers not only temporal resolution, but also the highest possible spatial resolution. Due to the high cost of its initial implementation, it has not been taken seriously. The work shows both simple and differential photonic side channel analyses. Then, it presents a fault attack against pairing-based cryptography. Due to the need for at least two indepe...

  18. Rapid Fear Detection Relies on High Spatial Frequencies

    NARCIS (Netherlands)

    Stein, T.; Seymour, K.; Hebart, M.N.; Sterzer, P.

    Signals of threat—such as fearful faces—are processed with priority and have privileged access to awareness. This fear advantage is commonly believed to engage a specialized subcortical pathway to the amygdala that bypasses visual cortex and processes predominantly low-spatial-frequency information

  19. Progress relies on sound information in the Philippines

    International Development Research Centre (IDRC) Digital Library (Canada)

    numerous out-of-school youth is based on HOPES — HIV prevention ... Loved, cared for and protected, Educated and empowered,. Savings ... provided the foundation for these and other programs. Carried out .... Promote gender equality.

  20. Working memory for conjunctions relies on the medial temporal lobe.

    Science.gov (United States)

    Olson, Ingrid R; Page, Katie; Moore, Katherine Sledge; Chatterjee, Anjan; Verfaellie, Mieke

    2006-04-26

    A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays.

  1. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  2. Indications of anti-HY immunity in recurrent placental abruption

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre; Mogensen, Marie; Steffensen, Rudi

    2007-01-01

    PROBLEM: Placental abruption is a potential life-threatening condition for both the fetus and the mother, being significantly more common in pregnancies with male fetuses. The pathogenesis of placental abruption remains unknown. However, some recent reports point toward a maternal immune response...... the fetus died. Seven patients (88%) had first-born boys, and 15 abruptions (68%) involved male fetuses. All patients with a first-born boy, except one, had HLA-class II alleles known to restrict CD4+ T-cell responses against male-specific minor histocompatibility (HY)-antigens (HLA-DRB1*15, HLA-DRB3...... abruption is exclusively almost preceded by the birth of a boy and the majority of patients have HLA-class II known to restrict CD4 T-cell reactions against HY-antigens. This indicates that maternal immunological responses against HY-antigens play a role in recurrent placental abruption. Udgivelsesdato...

  3. Origin of Aymaras from Bolivia and their relationship with other Amerindians according to HLA genes.

    Science.gov (United States)

    Arnaiz-Villena, A; Siles, N; Moscoso, J; Zamora, J; Serrano-Vela, J I; Gomez-Casado, E; Castro, M J; Martinez-Laso, J

    2005-04-01

    Aymara Amerindians from the Titicaca Lake Andean highlands are studied for HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 gene frequencies. Genetic distances, neighbour-joining and correspondence analyses are performed by using other Amerindian and worldwide populations (15384 chromosomes are studied). The HLA genetic profile of Aymaras is different from neighbouring and language-related Quechuas (Incas). Both Quechuas and Aymaras seem to present an HLA-DRB1*0901 high frequency, which is present in a very low frequency or absent in Mesoamericans (Mazatecans, Mayans) and most studied Amerindians. Moreover, it is observed a closer relatedness of Aymaras with Amerindians from the Amazon Basin and Chaco lowlands, compared to Quechuans.

  4. HLA class II alleles as markers of tuberculosis susceptibility and resistance

    Directory of Open Access Journals (Sweden)

    R. Duarte

    2011-01-01

    Full Text Available Background: Not every individual exposed to Mycobacterium tuberculosis becomes infected. One host genetic factor, involved in modulating the immune response that has been studied in many ethnic groups is the association of human leukocyte antigens (HLA with susceptibility to tuberculosis (TB. Objective: To investigate the association between TB, HLA-DRB1 and HLA-DQB1 alleles in a Portuguese population. Methods: HLA-DRB1 and HLA-DQB1 gene polymorphisms were analyzed by PCR-SSP in 92 TB patients, and 82 healthcare professionals without TB but exposed on a daily basis to infectious patients for more than two years (healthy exposed - HE. Tuberculin skin test reaction (TST, was positive in 69 individuals (all over 15 mm in the HE group (HE+ and negative in thirteen (HE−. Results: HLA-DRB1*14 frequency is higher in the TB patients group (7 % vs. 0; p = 0.038 than in HE+. Conclusions: No genetic marker clearly indicative of disease susceptibility or resistance was identified in this study. However, HLA-DRB1*14 was more frequent in TB patients suggesting that it may be involved in the evolution infection towards active TB in our population. Resumo: Introdução: Nem todos os indivíduos expostos ao Mycobacterium tuberculosis ficam infectados. Um dos factores genéticos envolvidos na modulação da resposta imune e estudado em muitos grupos étnicos é a associação entre moléculas HLA (human leukocyte antigens e a susceptibilidade à tuberculose (TB. Objectivo: Investigar a relação entre TB e os alelos HLA-DRB1, DQB1 numa população Portuguesa.Métodos: Os polimorfismos dos genes HLA-DRB1 e HLA-DQB1 foram analisados por PCR-SSP em 92 doentes com TB e 82 profissionais de saúde saudáveis, expostos diariamente a doentes baciliferos por um período superior a 2 anos (expostos saudáveis: ES. Neste grupo de ES, o teste tuberculínico foi positivo (TST = 10 mm em 69 indivíduos (todos

  5. Identification of NY-BR-1-specific CD4(+) T cell epitopes using HLA-transgenic mice.

    Science.gov (United States)

    Gardyan, Adriane; Osen, Wolfram; Zörnig, Inka; Podola, Lilli; Agarwal, Maria; Aulmann, Sebastian; Ruggiero, Eliana; Schmidt, Manfred; Halama, Niels; Leuchs, Barbara; von Kalle, Christof; Beckhove, Philipp; Schneeweiss, Andreas; Jäger, Dirk; Eichmüller, Stefan B

    2015-06-01

    Breast cancer represents the second most common cancer type worldwide and has remained the leading cause of cancer-related deaths among women. The differentiation antigen NY-BR-1 appears overexpressed in invasive mammary carcinomas compared to healthy breast tissue, thus representing a promising target antigen for T cell based tumor immunotherapy approaches. Since efficient immune attack of tumors depends on the activity of tumor antigen-specific CD4(+) effector T cells, NY-BR-1 was screened for the presence of HLA-restricted CD4(+) T cell epitopes that could be included in immunological treatment approaches. Upon NY-BR-1-specific DNA immunization of HLA-transgenic mice and functional ex vivo analysis, a panel of NY-BR-1-derived library peptides was determined that specifically stimulated IFNγ secretion among splenocytes of immunized mice. Following in silico analyses, four candidate epitopes were determined which were successfully used for peptide immunization to establish NY-BR-1-specific, HLA-DRB1*0301- or HLA-DRB1*0401-restricted CD4(+) T cell lines from splenocytes of peptide immunized HLA-transgenic mice. Notably, all four CD4(+) T cell lines recognized human HLA-DR-matched dendritic cells (DC) pulsed with lysates of NY-BR-1 expressing human tumor cells, demonstrating natural processing of these epitopes also within the human system. Finally, CD4(+) T cells specific for all four CD4(+) T cell epitopes were detectable among PBMC of breast cancer patients, showing that CD4(+) T cell responses against the new epitopes are not deleted nor inactivated by self-tolerance mechanisms. Our results present the first NY-BR-1-specific HLA-DRB1*0301- and HLA-DRB1*0401-restricted T cell epitopes that could be exploited for therapeutic intervention against breast cancer. © 2014 UICC.

  6. The Root Cause of Post-Traumatic and Developmental Stress Disorder

    Science.gov (United States)

    2014-10-01

    PTSD BA11 PTSD BA11 (Pɘ.023) and correlated to HLA-DRB3 mushroom spine density Nissl staining on whole hemisphere sections from the frontal...techniques. Initial golgi analysis of prefrontal anatomy and stereological studies of the frontal cortex in Nissl sections are in progress. Major...cortex/hippocampus of PTSD, MDD and controls, with 5HTTLPR and other genetic variants as cofactors. Fig A. Golgi staining (left) in the mOFCTX has been

  7. HLA-DQA1 and HLA-DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal).

    Science.gov (United States)

    Spínola, H; Lemos, A; Couto, A R; Parreira, B; Soares, M; Dutra, I; Bruges-Armas, J; Brehm, A

    2017-02-01

    This study shows, for the first time, high-resolution allele frequencies of HLA-DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA-A, HLA-B, HLA-DRB1, HLA-DQA1 and HLA-DQB1, are also reported. © 2016 John Wiley & Sons Ltd.

  8. Frecuencia de alelos HLA de clase I y II en una cohorte de pacientes

    Directory of Open Access Journals (Sweden)

    Eliana Patricia Velásquez

    2012-03-01

    Conclusión. Los alelos HLA-B27, HLA-DRB4*01 y HLA-DQB1*0501 fueron frecuentes en los diferentes subtipos de espondiloartritis y en las manifestaciones clínicas axiales, periféricas y extraarticulares específicas, además de la sacroiliítis radiológica.   DOI: http://dx.doi.org/10.7705/biomedica.v32i1.569

  9. The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

    OpenAIRE

    Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M.; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F.; Lopez-Nevot, Miguel A.; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

    2012-01-01

    Background: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. Methodology and Results: We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-...

  10. Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis.

    Directory of Open Access Journals (Sweden)

    Seungbok Lee

    Full Text Available Alopecia areata (AA is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10(-3. Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57 and rs28362679 of BTNL2 (p<0.001, OR 30.21. While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2 and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.

  11. Maternal HY-restricting HLA class II alleles are associated with poor long-term outcome in recurrent pregnancy loss after a boy.

    Science.gov (United States)

    Kolte, Astrid Marie; Steffensen, Rudi; Christiansen, Ole Bjarne; Nielsen, Henriette Svarre

    2016-11-01

    Women with secondary recurrent pregnancy loss (RPL) after a boy have a reduced chance of live birth in the first pregnancy after referral if they carry HY-restricting HLA class II alleles, but long-term chance of live birth is unknown. Live birth was compared for 540 women with unexplained secondary RPL according to firstborn's sex and maternal carriage of HLA-DRB3*03:01, HLA-DQB1*05:01/02, HLA-DRB1*15, and HLA-DRB1*07. The groups were compared by Cox proportional hazard ratios. For women with at firstborn boy, maternal carriage of HY-restricting HLA class II alleles decreased chance of live birth: 0 vs 1: hazard ratio 0.75 (95% CI 0.55-1.02); 0 vs 2: HR 0.62 (0.40-0.94). Carriage of HY-restricting HLA class II alleles decreased chance of live birth only if the firstborn was a boy: boy vs girl: HR 0.72 (95% CI 0.55-0.98). Maternal carriage of HY-restricting HLA class II alleles decreases long-term chance of live birth in women with RPL after a boy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Association between Age at Diagnosis of Graves' Disease and Variants in Genes Involved in Immune Response

    Science.gov (United States)

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Krol, Aleksandra; Bednarczuk, Tomasz; Kolosza, Zofia; Tukiendorf, Andrzej; Szpak-Ulczok, Sylwia; Stanjek-Cichoracka, Anita; Polanska, Joanna; Jarzab, Barbara

    2013-01-01

    Background Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. Methods 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. Results Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. Conclusions HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in polish population. PMID:23544060

  13. Association between age at onset of multiple sclerosis and vitamin D level-related factors

    DEFF Research Database (Denmark)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2016-01-01

    OBJECTIVE: To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset. METHODS: This cross......, and the study was approved by the local ethics committee. RESULTS: Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher body mass index at 20 years of age, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis....... No association was found between age at onset and any of the other SNPs or vitamin D-associated environmental factors. CONCLUSION: We demonstrate an independent effect by HLA-DRB1*1501, adolescent summer sun habits, and body mass index at the age of 20 on age at onset of MS....

  14. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

    Directory of Open Access Journals (Sweden)

    Suella Martino

    Full Text Available Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP. Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04. Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all. Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03. Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.

  15. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

    Science.gov (United States)

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.

  16. HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.

    Science.gov (United States)

    Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando

    2006-12-01

    Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.

  17. Epidemiology of human leukocyte antigens among omani population.

    Science.gov (United States)

    Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

    2017-01-01

    Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

  18. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

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    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  19. Epidemiology of human leukocyte antigens among omani population

    Directory of Open Access Journals (Sweden)

    Issa Al Salmi

    2017-01-01

    Full Text Available Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation years for the cohort were 33.2 (13.0. Males constituted 56.3% (490 while females constituted 43.7% (380. Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%, followed by HLA A11 (9.4%, and A32 (8.1%. Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%, followed by HLA-B-35 (13.6%, and HLA-B8 (7.9%. Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%. This was followed by HLA-DRB1*03 (14.57% and HLA-DRB1*11 (9.48%. While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%. This was followed by allele HLA-DQB1*02 (26.48% and HLA-DQB1*03 (17.18%. This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

  20. Okuma Gelişiminde Üst Dil Farkındalığı, Sesbilgisel Süreçler ve Bellek Süreçlerinin Etkisi: Kısa Süreli Bellek ve Çalışma Belleği

    Directory of Open Access Journals (Sweden)

    Filiz Sayar

    2012-07-01

    Full Text Available Bu makalede, alanyazında okuma gelişimini belirleyen üstdil farkındalığı, sesbilgisel beceriler ile bellek işlevlerine yer veren araştırmalar incelenmiştir. Bu bilişsel süreçler, karmaşık bir süreç olan okuma gelişimini farklı şekilde etkilemektedir. Bu makalede ele alınan araştırmalarda, başarılı bir okuma performansı için üstdil farkındalığının gerekli olduğu sonucuna ulaşılırken; üstdil farkındalığı becerilerinden sesbilgisel farkındalığın okumanın en güçlü yordayıcısı olduğu konusunda fikirbirliği sağlanmıştır. Okuma gelişimi ile kısa-süreli bellek ve çalışma belleği ilişkisini inceleyen araştırmalar ise, çalışma belleğinin kısa-süreli belleğe göre okumada daha etkili olduğu yönünde bulgular elde etmişlerdir. Diğer yandan, okuma gelişimi konusunda çalışmalarını yürüten bazı araştırmacılar, okumanın çok yönlü ve çoklu-etkenli olması nedeniyle okuma gelişimini belirleyecek tek ve en güçlü bilişsel etmenin bulunamayacağını ifade etmişlerdir. The research in the literature dealing with metalinguistic awareness, phonological abilities and memory functions determinig reading development were examined in this article. These cognitive processes determine differently reading that is a complicated process. The research stated in this article suggested that metalinguistic awareness was crucial for successful reading performance and agreed that phonological awareness one of the metalinguistic abilities was the most powerful predictor of reading. The research examining short-term memory and working memory with reading development obtained some evidence that working memory was more influential on reading than short-term memory. On the other hand, some researchers searching on reading development stated that unique and the most powerful cognitive factor predicting reading development could not be found because reading was multidirectional and

  1. HLA-DR alleles among Pakistani patients of coeliac disease

    International Nuclear Information System (INIS)

    Saleem, N.; Ahmed, T.A.; Bashir, M.; Ali, S.; Iqbal, M.

    2013-01-01

    Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

  2. The Royan Public Umbilical Cord Blood Bank: Does It Cover All Ethnic Groups in Iran Based on HLA Diversity?

    Science.gov (United States)

    Ebrahimkhani, Saeideh; Farjadian, Shirin; Ebrahimi, Marzieh

    2014-04-01

    Umbilical cord blood (UCB) stem cells allow the transplantation of partially human leukocyte antigen (HLA)-matched grafts and are a valuable resource for the treatment of hematologic malignancies and heritable hematologic, immunologic and metabolic diseases, especially when a compatible bone marrow donor is unavailable. The aim of this study was to determine how many ethnic groups in Iran are covered by the available UCB units based on HLA diversity. From 2009 until mid-2013, 4,981 (30.3%) of the 16,437 UCB samples collected met the storage criteria and were cryopreserved at a public cord blood bank (CBB) in Tehran, Iran. HLA-A, -B and -DRB1 were typed in 1,793 samples. The mean volume of the cryopreserved samples was 81.25 ± 20.3 ml. The range of total nucleated cells per unit was 51 × 10(7)-107 × 10(7). The most common HLA alleles were HLA-A*2 (17%) and HLA-A*24 (15.6%), HLA-B*35 (16.8%) and HLA-B*51 (13.9%), and HLA-DRB1*11 (20%) and HLA-DRB1*15 (14%). The predominant haplotypes were HLA-A*24-B*35-DRB1*11 (2%), HLA-A*02-B*50-DR*07 (1.8%), and HLA-A*02-B*51-DRB1*11 (1.5%). Based on the HLA-DRB1 profiles, the UCB units available at the Royan public UCB bank are a potentially adequate resource for hematopoietic stem cell transplantation for Iranian recipients belonging to particular ethnic groups. Regular educational programs to improve the public knowledge of UCB for transplantation can enhance the public CBB stocks for all Iranian ethnic groups in the future.

  3. CYP21A2 polymorphisms in patients with autoimmune Addison's disease, and linkage disequilibrium to HLA risk alleles.

    Science.gov (United States)

    Brønstad, Ingeborg; Skinningsrud, Beate; Bratland, Eirik; Løvås, Kristian; Undlien, Dag; Sverre Husebye, Eystein; Wolff, Anette Susanne Bøe

    2014-12-01

    Steroid 21-hydroxylase, encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the HLA complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Genotyping of CYP21A2 was carried out by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Heterozygotes of the single-nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared with HC (P<0.005), but all SNPs were in a linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (odds ratio=0.15, 95% CI (0.08-0.30), P=3.8×10(-10)). This SNP was not in an LD with HLA loci (P=0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in <1.5% of the cases in both groups. Genetic variants of CYP21A2 associated to AAD are in LD with the main AAD risk locus HLA-DRB1, and CYP21A2 does not constitute an independent susceptibility locus. © 2014 European Society of Endocrinology.

  4. Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis.

    Science.gov (United States)

    Niu, Zhili; Zhang, Pingan; Tong, Yongqing

    2015-01-01

    Human leukocyte antigen (HLA)-DRB1 allele polymorphisms have been reported to be associated with systemic lupus erythematosus (SLE) susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to systematically summarize and explore whether specific HLA-DRB1 alleles confer susceptibility or resistance to SLE and lupus nephritis. This review was guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach. A comprehensive search was made for articles from PubMed, Medline, Elsevier Science, Springer Link and Cochrane Library database. A total of 25 case-control studies on the relationship between gene polymorphism of HLA-DRB l and SLE were performed and data were analyzed and processed using Review Manager 5.2 and Stata 11.0. At the allelic level, HLA-DR4, DR11 and DR14 were identified as protective factors for SLE (0.79 [0.69,0.91], P  0.05). DR4 and 11 (OR, 0.55 [0.39, 0.79], P  0.05; 0.90 [0.64, 1.27], P > 0.05; 0.61 [0.36, 1.03], P > 0.05, respectively) were not statistically significant between the lupus nephritis and control groups. The HLA-DR4, DR11, DR14 alleles might be protective factors for SLE and HLA-DR3, DR9, DR15 were potent risk factors. In addition, HLA-DR4 and DR11 alleles might be protective factors for lupus nephritis and DR3 and DR15 suggest a risk role. These results proved that HLA-DR3, DR15, DR4 and DR11 might be identified as predictors for lupus nephritis and SLE. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  5. Distinct HLA associations of LGI1 and CASPR2-antibody diseases.

    Science.gov (United States)

    Binks, Sophie; Varley, James; Lee, Wanseon; Makuch, Mateusz; Elliott, Katherine; Gelfand, Jeffrey M; Jacob, Saiju; Leite, M Isabel; Maddison, Paul; Chen, Mian; Geschwind, Michael D; Grant, Eleanor; Sen, Arjune; Waters, Patrick; McCormack, Mark; Cavalleri, Gianpiero L; Barnardo, Martin; Knight, Julian C; Irani, Sarosh R

    2018-05-18

    The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA-DRB1*07:01 was strongly represented [odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 × 10-26]. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 [odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 × 10-6]. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1-derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation.

  6. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo

    OpenAIRE

    Cavalli, Giulio; Hayashi, Masahiro; Jin, Ying; Yorgov, Daniel; Santorico, Stephanie A.; Holcomb, Cherie; Rastrou, Melinda; Erlich, Henry; Tengesdal, Isak W.; Dagna, Lorenzo; Neff, C. Preston; Palmer, Brent E.; Spritz, Richard A.; Dinarello, Charles A.

    2016-01-01

    Vitiligo is a classic autoimmune disease genetically associated with SNPs in the MHC class II region. To date, the impact of HLA molecules on autoimmunity has focused on structural diversity of antigen presentation. Here, we describe the properties of a 47-nucleotide high-risk haplotype of three SNPs within an intergenic “super-enhancer” located between the HLA-DRB1 and HLA-DQA1 genes, localized by a genome-wide association study of 2,853 subjects with vitiligo. Monocytes from healthy subject...

  7. DNA polymorphism of HLA class II genes in primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Morling, Niels; Dalhoff, K; Fugger, L

    1992-01-01

    We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary...... than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC...

  8. Inflammation aggravates disease severity in Marfan syndrome patients.

    Directory of Open Access Journals (Sweden)

    Teodora Radonic

    Full Text Available BACKGROUND: Marfan syndrome (MFS is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-β signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-β and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-β and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-β were found especially in MFS patients with aortic root dilatation (124 pg/ml, when compared to MFS patients with normal aorta (10 pg/ml; p = 8×10(-6, 95% CI: 70-159 pg/ml. Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR = 0%, ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC = 1.8; 1.4; 1.5, FDR = 0% and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%. Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02 and increased number of CD8+ T-cells (p = 0.003 in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients.

  9. Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tamai, Yotaro; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki-Ryang; Nakamae, Hirohisa; Suehiro, Youko; Kato, Koji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari

    2013-04-15

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We previously reported that Tax-specific CD8(+) cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4(+) T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4(+) as well as CD8(+) T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4(+) T cell responses, we identified a novel HLA-DRB1*0101-restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4(+) Th1-like cells, a major population of HTLV-1-specific CD4(+) T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8(+) T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101(+) patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4(+) T cells were present in all HTLV-1-infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4(+) T cells in HLA-DRB1*0101(+)-infected individuals and that Tax-specific CD4(+) T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8(+) T cell responses.

  10. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

    DEFF Research Database (Denmark)

    George, Michaela F; Briggs, Farren B S; Shao, Xiaorong

    2016-01-01

    associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. CONCLUSIONS......OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded...

  11. Genetic diversity through human leukocyte antigen typing in end-stage renal disease patients and prospective donors of North India

    Directory of Open Access Journals (Sweden)

    Mohit Chowdhry

    2016-01-01

    Full Text Available As the incidence of end-stage renal disease (ESRD is rapidly increasing, the demand for dialysis and transplantation has dramatically increased, which has led to concerns about the availability and equitable allocation of kidneys for transplantation. The distribution of HLA-A, B and DR alleles in 148 renal transplant recipients and 191 live related prospective donors from 2009 to 2010 were analyzed. Allele frequencies and haplotype frequencies were calculated in recipients and donors. The prospective donors were further analyzed on the basis of their relationship to the patients and according to the sex ratio. A significant female preponderance was noted in the prospective donor population, most of whom were either siblings or parents of the recipients. On the contrary, the recipient population predominantly comprised of males. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in renal transplant patients were HLA-AFNx0111, AFNx0102, AFNx0101, AFNx0124; HLA-BFNx0135, BFNx0140, BFNx0144, BFNx0115, BFNx0152, and HLA-DRB1FNx0115, DRB1FNx0107, DRB1FNx0113, DRB1FNx0111 respectively. The most frequent HLA-A, HLA-B, HLA-DRB1 alleles in prospective donors were HLA-AFNx0102, AFNx0111, AFNx0133, AFNx0124; HLA-BFNx0135, BFNx0144, BFNx0140, BFNx0115 and HLA-DRB1FNx0115, DRB1FNx0107, DRB1FNx0111, DRB1FNx0113 respectively. AFNx0111-BFNx0135, AFNx0102-DRB1FNx0115, BFNx0140-DRB1FNx0115 were the most common HLA A-B , HLA A-DR, HLA B-DR haplotypes respectively in renal transplant patients, whereas, AFNx0111-BFNx0135, AFNx0111-DRB1FNx0115, BFNx0144-DRB1FNx0107 were the most common haplotypes in renal donors. In three locus haplotype, HLA-AFNx0102-BFNx0140-DRB1FNx0115 was the most frequent haplotype in patients, whereas, in prospective renal donors HLA-AFNx0133-BFNx0144-DRB1FNx0107 was the most frequent haplotype.

  12. Genetiske risikofaktorer for abortus habitualis og obstetriske komplikationer

    DEFF Research Database (Denmark)

    Christiansen, Ole Bjarne

    2010-01-01

    for a HLA-G14 basepair insertion is more frequent than in controls. In patients with a first-born boy carrying HLA class II alleles restricting recognition of HY antigens, the live-birth rate is low. Women with these risk genes also have an increased risk of delivering children with a low birth weight.......Maternal risk factors dominate among younger women with multiple miscarriages. In all patients, genetic variants associated with low plasma mannose binding lectin or thrombophilia affect the prognosis negatively. In women with secondary recurrent miscarriage, the HLA-DRB1*03 allele or homozygocity...

  13. HLA-A, -B, -DRB1 allele and haplotype frequencies of 920 cord blood units from Central Chile.

    Science.gov (United States)

    Schäfer, Christian; Sauter, Jürgen; Riethmüller, Tobias; Kashi, Zahra Mehdizadeh; Schmidt, Alexander H; Barriga, Francisco J

    2016-08-01

    We present human leukocyte antigen (HLA) haplotype and allele/antigenic group frequencies derived from a data set of 920 umbilical cord blood units collected in Central Chile. HLA-A and -B genotypes were typed using sequence specific oligonucleotide probe methods while HLA-DRB1 genotypes were obtained from sequencing-based typing. The most frequent haplotype is A*29~B*44~DRB1*07:01 with an estimated frequency of 2.1%. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  14. Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.

    Science.gov (United States)

    Brill, Livnat; Mandel, Micha; Karussis, Dimitrios; Petrou, Panayiota; Miller, Keren; Ben-Hur, Tamir; Karni, Arnon; Paltiel, Ora; Israel, Shoshana; Vaknin-Dembinsky, Adi

    2016-04-15

    Previous studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes. To evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD). The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls. Our data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002). Our findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with

  15. DNA typing of HLA class II genes in native inhabitants of Chukotka

    Energy Technology Data Exchange (ETDEWEB)

    Krylov, M.Yu.; Erdesz, S.; Alexeeva, L.I. [Institute of Rheumatology, Moscow (Russian Federation)

    1995-06-01

    Polymorphism of HLA class II genes was studied in native Chukotka inhabitants with the use of DNA oligotyping. The characteristics of the distribution of allelic variants of the loci HLA-DRB1, -DQA1, -DQB1, and -DPB1 were revealed; they were similar to those of other Subarctic Mongoloid populations and different from those for comparable populations of other climatic and geographic zones. Our data suggest that the specific features found for the distributions of some alleles of the loci examined are related to the geographic variation in the HLA gene system studied. 20 refs., 4 tabs.

  16. GENETIC POLYMORPHISM AND CYTOGENETIC CHANGES IN THE PERIPHERAL BLOOD T-LYMPHOCYTES OF PATIENTS WITH ARTHRITIS ASSOCIATED WITH IXODES TICK-BORNE BORRELIOSIS IN THE NORTHERN REGIONS OF SIBERIA

    Directory of Open Access Journals (Sweden)

    N. N. Ilyinskikh

    2017-01-01

    Full Text Available The authors have previously conducted studies that demonstrate the increased level of cytogenetic disturbances in patients with Ixodes tick-borne borreliosis (ITB. The severity of arthritis associated with ITB (AITB is also ascertained to depend on whether the patient has certain HLA-DRB1 alleles.Objective: to assess the association between HLA-DRB1 gene polymorphism and cytogenetic changes in the peripheral blood T lymphocytes of patients with AITB.Subjects and methods. 146 patients with AITB, 100 clinically healthy convalescents with ITB (CITB, and a control group of 98 healthy blood donors (HBDs without a history of tick-borne infections were examined using cytogenetic (micronucleus analysis of cytokinesis-blocked peripheral blood T lymphocytes and molecular genetic (PCR analysis of HLA-DRB1 gene polymorphism methods.Results and discussion. The frequency of cytokinesis-blocked lymphocytes with micronuclei in the AITB group was significantly higher than that in the CITB and HBD groups (p<0.01 with the exception of the results obtained in the subgroup of patients with AITB who had the DRB1*10 allele (p>0.05. The highest levels of lymphocytes with micronuclei were observed in AITB patients with the DRB1*17(03, *01, and *04 alleles as compared to those in the CITB and HBD groups (p<0.001. The CITB group showed the most significant increase in the detection rate of lymphocytes with micronuclei in people with the DRB1*01, DRB1*04, or *17(03 alleles. At the same time, there were no significant differences in the number of lymphocytes with micronuclei in the HBD group, depending on the HLA-DRB1 gene alleles (p>0.05. Thus, the patients with AITB had the highest frequency of cytogenetic disorders with the exception of individuals with the DRB1*10 allele.

  17. Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

    Science.gov (United States)

    Venkateswaran, Suresh; Prince, Jarod; Cutler, David J; Marigorta, Urko M; Okou, David T; Prahalad, Sampath; Mack, David; Boyle, Brendan; Walters, Thomas; Griffiths, Anne; Sauer, Cary G; LeLeiko, Neal; Keljo, David; Markowitz, James; Baker, Susan S; Rosh, Joel; Pfefferkorn, Marian; Heyman, Melvin B; Patel, Ashish; Otley, Anthony; Baldassano, Robert; Noe, Joshua; Rufo, Paul; Oliva-Hemker, Maria; Davis, Sonia; Zwick, Michael E; Gibson, Greg; Denson, Lee A; Hyams, Jeffrey; Kugathasan, Subra

    2018-03-19

    The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59). To study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC. HLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13). In pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

  18. 77 FR 39561 - Advanced Braking Technologies That Rely on Forward-Looking Sensors; Request for Comments

    Science.gov (United States)

    2012-07-03

    .... Mail: Docket Management Facility, U.S. Department of Transportation, 1200 New Jersey Avenue SE., West... surrogate vehicles representing various vehicle body styles that any system would encounter in the real world to ensure robustness? If there is such a need, describe what body styles should comprise the fleet...

  19. Does the applicability of Bacillus strains in probiotics rely upon their taxonomy?

    Science.gov (United States)

    Safronova, L A; Zelena, L B; Klochko, V V; Reva, O N

    2012-02-01

    The taxonomic position and biological activities of two Bacillus strains used in veterinary probiotics were studied in this work. These microorganisms inhibit growth of a broad spectrum of pathogenic cultures. They synthesize proteolytic enzymes and other biologically active metabolites, and to some extent, supplement each other with probiotic activities. It is not clear whether these versatile activities are properties of individual strains or bacterial taxa as whole. 16S rRNA comparisons were conducted and illustrated the relatedness of these strains to Bacillus amyloliquefaciens . Their cell wall fatty acid contents were consequently analysed and specified a relation to the " Bacillus velezensis " ecomorph. On account of the previous observations, a simple method of 16S rRNA profiling by polymorphic nucleotides was proposed to determine a group of organisms closely related to "B. velezensis" and B. amyloliquefaciens subsp. plantarum, for they are biologically active strains suitable for use in biotechnology. The extreme genetic plasticity of these bacteria endowed each strain with a unique spectrum of antagonistic activity.

  20. Enhancing memory performance after organic brain disease relies on retrieval processes rather than encoding or consolidation

    NARCIS (Netherlands)

    Hildebrandt, H.; Gehrmann, A.; Mödden, C.; Eling, P.A.T.M.

    2011-01-01

    Neuropsychological rehabilitation of memory performance is still a controversial topic, and rehabilitation studies have not analyzed to which stage of memory processing (encoding, consolidation, or retrieval) enhancement may be attributed. We first examined the efficacy of a computer training

  1. Persistent identifiers for web service requests relying on a provenance ontology design pattern

    Science.gov (United States)

    Car, Nicholas; Wang, Jingbo; Wyborn, Lesley; Si, Wei

    2016-04-01

    Delivering provenance information for datasets produced from static inputs is relatively straightforward: we represent the processing actions and data flow using provenance ontologies and link to stored copies of the inputs stored in repositories. If appropriate detail is given, the provenance information can then describe what actions have occurred (transparency) and enable reproducibility. When web service-generated data is used by a process to create a dataset instead of a static inputs, we need to use sophisticated provenance representations of the web service request as we can no longer just link to data stored in a repository. A graph-based provenance representation, such as the W3C's PROV standard, can be used to model the web service request as a single conceptual dataset and also as a small workflow with a number of components within the same provenance report. This dual representation does more than just allow simplified or detailed views of a dataset's production to be used where appropriate. It also allow persistent identifiers to be assigned to instances of a web service requests, thus enabling one form of dynamic data citation, and for those identifiers to resolve to whatever level of detail implementers think appropriate in order for that web service request to be reproduced. In this presentation we detail our reasoning in representing web service requests as small workflows. In outline, this stems from the idea that web service requests are perdurant things and in order to most easily persist knowledge of them for provenance, we should represent them as a nexus of relationships between endurant things, such as datasets and knowledge of particular system types, as these endurant things are far easier to persist. We also describe the ontology design pattern that we use to represent workflows in general and how we apply it to different types of web service requests. We give examples of specific web service requests instances that were made by systems at Australia's National Computing Infrastructure and show how one can 'click' through provenance interfaces to see the dual representations of the requests using provenance management tooling we have built.

  2. The power of hope: being a doctor is more than relying solely on the numbers.

    Science.gov (United States)

    Godshalk, A N; Brown, G C; Brown, H C; Brown, M M

    2008-06-01

    To ascertain whether a physician's positive or negative attitude significantly impacts the quality of life of ophthalmic patients. A standardised, validated, time trade-off, utility instrument was administered to consecutive vitreoretinal patients by interview to assess the quality of life associated with their current ocular health state (baseline scenario). Each was then given a scenario for the exact same health state with the same long-term prognosis in which their doctor emphasised the possible negative consequences (bad-news scenario) and one for the same health state in which their doctor emphasised the positive consequences (good-news scenario). Among the 247 patients enrolled were 140 women (57%) and 107 men (43%) with a mean age of 66 years and a mean educational level of 13.8 years after kindergarten. The mean baseline utility for 247 patients was 0.87 (SD = 0.19; 95% CI 0.84 to 0.89). The mean bad-news scenario utility was 0.80 (SD = 0.22, 95% CI 0.78 to 0.83), a 70% diminution in quality of life compared with the mean baseline utility (p = 0.0009). The mean good-news scenario utility was 0.89 (SD = 0.18, 95% CI 0.86 to 0.91), an insignificant difference compared with the mean baseline utility (p = 0.26). Ocular patients had a considerably poorer quality of life when their physician emphasised the possible negative consequences associated with their eye disease(s), as opposed to a more positive approach. While at times necessary, a negative emphasis approach can theoretically result in a considerable loss of life's value.

  3. Monkeys Rely on Recency of Stimulus Repetition When Solving Short-Term Memory Tasks

    Science.gov (United States)

    Wittig, John H., Jr.; Richmond, Barry J.

    2014-01-01

    Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best…

  4. Gustatory Habituation in "Drosophila" Relies on "Rutabaga" (Adenylate Cyclase)-Dependent Plasticity of GABAergic Inhibitory Neurons

    Science.gov (United States)

    Paranjpe, Pushkar; Rodrigues, Veronica; VijayRaghavan, K.; Ramaswami, Mani

    2012-01-01

    In some situations, animals seem to ignore stimuli which in other contexts elicit a robust response. This attenuation in behavior, which enables animals to ignore a familiar, unreinforced stimulus, is called habituation. Despite the ubiquity of this phenomenon, it is generally poorly understood in terms of the underlying neural circuitry. Hungry…

  5. Improving listening comprehension skills relying on metacognitive strategies - focus on vocabulary and specific l2 instruction

    Directory of Open Access Journals (Sweden)

    Jerotijević-Tišma Danica

    2016-01-01

    Full Text Available The present paper aims at investigating the application of an instructional method specifically focused on the expansion of metacognitive awareness and its effect on Serbian EFL students’ listening comprehension. The current study is a follow-up research of a similar study by Vandergrift and Tafaghodtari (2010. However, we sought to expand the previous research by investigating the relationship between the students’ current level of L2 (target language vocabulary and listening test scores. Our study likewise differed in the sample of participants, the target language, teaching and testing material used, and the duration of the very experiment. To answer the proposed research questions we conducted an experiment with 57 Serbian secondary school EFL (English as a Foreign Language learners divided into experimental (n=27 and control group (n=30. The results of the pre- and post-tests of the two groups showed the beneficial effects of developing metacognitive strategies and the strong positive correlation between the level of vocabulary and listening comprehension. The paper underlines important pedagogical implications especially regarding the enhancement of metacognitive awareness and vocabulary proficiency of students in order to improve performance on listening comprehension tasks.

  6. DESIGN OF DYNAMIC VOLTAGE RESTORER TO ENHANCE POWER QUALITY RELYING ON RENEWABLE SOURCE

    Directory of Open Access Journals (Sweden)

    Haider M. Umran

    2018-05-01

    Full Text Available Power quality improvement of low voltage grid is a great challenge that confronts the sophisticated power applications, because their performance is highly sensitive to the quality of power supply. Dynamic Voltage Restorer (DVR used widely as an efficient and skillful device to adjust electrical disturbances of the distribution grids. This paper introduces an overview of the components of the 3-phase dynamic voltage restorer and design its own control circuit. The performance of DVR was developed on the basis of the appropriate selection of Photovoltaic (PV module instead of the present conventional designs. Through this design, the need of series converter (DVR for the current from an electrical grid will end and the problems of power losses will curb. The PV-module is selected to meet the requirements of the DVR during voltage sag/swell on voltage line. The proposed system is mimicked in MATLAB software/Simulink and the findings are presented to prove the success of the design in terms of: Full congruence of the load voltage waveform with source voltage waveform, attaining 0.77% of THD analysis for the load voltage and the waveforms of PV system.

  7. Arsenate tolerance in Silene paradoxa does not rely on phytochelatin-dependent sequestration

    International Nuclear Information System (INIS)

    Arnetoli, Miluscia; Vooijs, Riet; Bookum, Wilma ten; Galardi, Francesca; Gonnelli, Cristina; Gabbrielli, Roberto; Schat, Henk; Verkleij, Jos A.C.

    2008-01-01

    Arsenate tolerance, As accumulation and As-induced phytochelatin accumulation were compared in populations of Silene paradoxa, one from a mine site enriched in As, Cu and Zn, the other from an uncontaminated site. The mine population was significantly more arsenate-tolerant. Arsenate uptake and root-to-shoot transport were slightly but significantly higher in the non-mine plants. The difference in uptake was quantitatively insufficient to explain the difference in tolerance between the populations. As accumulation in the roots was similar in both populations, but the mine plants accumulated much less phytochelatins than the non-mine plants. The mean phytochelatin chain length, however, was higher in the mine population, possibly due to a constitutively lower cellular glutathione level. It is argued that the mine plants must possess an arsenic detoxification mechanism other than arsenate reduction and subsequent phytochelatin-based sequestration. This alternative mechanism might explain at least some part of the superior tolerance in the mine plants. - Neither decreased uptake nor phytochelatins seem to play a role in the As tolerance in Silene paradoxa

  8. Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2 activity

    DEFF Research Database (Denmark)

    Köpper, Frederik; Bierwirth, Cathrin; Schön, Margarete

    2013-01-01

    knockdown of the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected cells from DNA damage-induced cell death, and mice deficient for MK2 displayed decreased apoptosis in the skin upon UV irradiation...

  9. Wide dispersal of aphid-pathogenic Entomophthorales among aphids relies upon migratory alates.

    Science.gov (United States)

    Feng, Ming-Guang; Chen, Chun; Chen, Bin

    2004-05-01

    Entomophthoralean mycoses are of general importance in the natural control of aphids, but mechanisms involved in their dissemination are poorly understood. Despite several possible means of fungal survival, the dispersal of the mycoses in aphids has never been related to the flight of their migratory alates that are able to locate suitable host plants. In this study, aphid-pathogenic fungi proved to be widely disseminated among various aphids by their alates through migratory flight based on the following findings. First, up to 36.6% of the 7139 migratory alates (including nine species of vegetable or cereal aphids) trapped from air > 30 m above the ground in three provinces of China were found bearing eight species of fungal pathogens. Of those, six were aphid-specific Entomophthorales dominated in individual cases by Pandora neoaphidis, which occurs globally but has no resting spores discovered to date. Secondly, infected alates were confirmed to be able to fly for hours, to initiate colonies on plants after flight and to transmit fungal infection to their offspring in a laboratory experiment, in which 238 Sitobion avenae alates were individually flown in a computer-monitoring flight mill system after exposure to a spore shower of P. neoaphidis and then allowed to colonize host plants.

  10. Something To Rely On : The Influence of Stable and Fleeting Drivers on Moral Behavior

    NARCIS (Netherlands)

    G.G. van Houwelingen (Gijs)

    2015-01-01

    markdownabstract__Abstract__ In virtually any situation we are bound to encounter short-lived influences that lure us to act in a certain way. The influence of such ‘fleeting drivers’ may or may not be in line our long-term goals and commitments (‘stable drivers’). Moral behaviour in particular

  11. Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

    Science.gov (United States)

    Gaya, Mauro; Barral, Patricia; Burbage, Marianne; Aggarwal, Shweta; Montaner, Beatriz; Warren Navia, Andrew; Aid, Malika; Tsui, Carlson; Maldonado, Paula; Nair, Usha; Ghneim, Khader; Fallon, Padraic G; Sekaly, Rafick-Pierre; Barouch, Dan H; Shalek, Alex K; Bruckbauer, Andreas; Strid, Jessica; Batista, Facundo D

    2018-01-25

    B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

    International Nuclear Information System (INIS)

    Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

    2011-01-01

    The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

  13. Relying on Your Own Best Judgment: Imputing Values to Missing Information in Decision Making.

    Science.gov (United States)

    Johnson, Richard D.; And Others

    Processes involved in making estimates of the value of missing information that could help in a decision making process were studied. Hypothetical purchases of ground beef were selected for the study as such purchases have the desirable property of quantifying both the price and quality. A total of 150 students at the University of Iowa rated the…

  14. Permissive and instructive anterior patterning rely on mRNA localization in the wasp embryo.

    Science.gov (United States)

    Brent, Ava E; Yucel, Gozde; Small, Stephen; Desplan, Claude

    2007-03-30

    The long-germ mode of embryogenesis, in which segments arise simultaneously along the anteriorposterior axis, has evolved several times in different lineages of the holometabolous, or fully metamorphosing, insects. Drosophila's long-germ fate map is established largely by the activity of the dipteran-specific Bicoid (Bcd) morphogen gradient, which operates both instructively and permissively to accomplish anterior patterning. By contrast, all nondipteran long-germ insects must achieve anterior patterning independently of bcd. We show that bcd's permissive function is mimicked in the wasp by a maternal repression system in which anterior localization of the wasp ortholog of giant represses anterior expression of the trunk gap genes so that head and thorax can properly form.

  15. Enabling Eco-Friendly Choices by Relying on the Proportional-Thinking Heuristic

    Directory of Open Access Journals (Sweden)

    Cleotilde Gonzalez

    2013-01-01

    Full Text Available Ecological (eco taxes are promising mechanisms to enable eco-friendly decisions, but few people prefer them. In this study, we present a way in which eco-tax options may be communicated to general public to encourage their payment. Our implementation (called “information presentation” takes advantage of the non-linear relationship between eco-tax payments and CO2 emissions and the human reliance on the proportional-thinking heuristic. According to the proportional-thinking heuristic, people are likely to prefer a small eco-tax increase and judge larger eco-tax increases to cause proportionally greater CO2 emissions reductions. In an online study, participants were asked to choose between eco-tax increases in two problems: In one, a smaller eco-tax increase resulted in greater CO2 emissions reduction, while in the other, a smaller tax increase resulted in lesser CO2 emissions reduction. Although the larger eco-tax increase did not reduce CO2 emissions the most, across both problems, people judged larger eco-tax increases to cause proportionally greater reductions in CO2 emissions and preferred smaller tax increases. Thus, eco-tax policies would benefit by presenting information in terms of eco-tax increases, such that smaller eco-tax increases (which are more attractive and are likely to be chosen by people cause greater CO2 emissions reductions.

  16. High-fidelity DNA replication in Mycobacterium tuberculosis relies on a trinuclear zinc center.

    Science.gov (United States)

    Baños-Mateos, Soledad; van Roon, Anne-Marie M; Lang, Ulla F; Maslen, Sarah L; Skehel, J Mark; Lamers, Meindert H

    2017-10-11

    High-fidelity DNA replication depends on a proofreading 3'-5' exonuclease that is associated with the replicative DNA polymerase. The replicative DNA polymerase DnaE1 from the major pathogen Mycobacterium tuberculosis (Mtb) uses its intrinsic PHP-exonuclease that is distinct from the canonical DEDD exonucleases found in the Escherichia coli and eukaryotic replisomes. The mechanism of the PHP-exonuclease is not known. Here, we present the crystal structure of the Mtb DnaE1 polymerase. The PHP-exonuclease has a trinuclear zinc center, coordinated by nine conserved residues. Cryo-EM analysis reveals the entry path of the primer strand in the PHP-exonuclease active site. Furthermore, the PHP-exonuclease shows a striking similarity to E. coli endonuclease IV, which provides clues regarding the mechanism of action. Altogether, this work provides important insights into the PHP-exonuclease and reveals unique properties that make it an attractive target for novel anti-mycobacterial drugs.The polymerase and histidinol phosphatase (PHP) domain in the DNA polymerase DnaE1 is essential for mycobacterial high-fidelity DNA replication. Here, the authors determine the DnaE1 crystal structure, which reveals the PHP-exonuclease mechanism that can be exploited for antibiotic development.

  17. Dog and human inflammatory bowel disease rely on overlapping yet distinct dysbiosis networks.

    Science.gov (United States)

    Vázquez-Baeza, Yoshiki; Hyde, Embriette R; Suchodolski, Jan S; Knight, Rob

    2016-10-03

    Inflammatory bowel disease (IBD) is an autoimmune condition that is difficult to diagnose, and animal models of this disease have questionable human relevance 1 . Here, we show that the dysbiosis network underlying IBD in dogs differs from that in humans, with some bacteria such as Fusobacterium switching roles between the two species (as Bacteroides fragilis switches roles between humans and mice) 2 . For example, a dysbiosis index trained on humans fails when applied to dogs, but a dog-specific dysbiosis index achieves high correlations with the overall dog microbial community diversity patterns. In addition, a random forest classifier trained on dog-specific samples achieves high discriminatory power, even when using stool samples rather than the mucosal biopsies required for high discriminatory power in humans 2 . These relationships were not detected in previously published dog IBD data sets due to their limited sample size and statistical power 3 . Taken together, these results reveal the need to train host-specific dysbiosis networks and point the way towards a generalized understanding of IBD across different mammalian models.

  18. Cochrane and its prospects in Bosnia and Herzegovina: Relying on Cochrane Croatia.

    Science.gov (United States)

    Mahmić-Kaknjo, Mersiha; Puljak, Livia; Markotić, Filipa; Fidahić, Mahir; Muhamedagić, Lejla; Zakarija-Grković, Irena

    2015-01-01

    In this article we describe Cochrane and its products: Cochrane systematic reviews (CSRs) and other Cochrane evidence. Cochrane is a unique, international, non-profit organisation that offers health care providers, health care consumers and other decision makers unbiased and highly reliable information on health, which is pivotal for conscientious and responsible decision making in overall healthcare. Cochrane offers the highest ranked evidence in Evidence Based Medicine (EBM)--systematic reviews. Currently, CSRs are freely available in BH, and therefore, they ought to be widely used, and understood. We will present the new Cochrane Strategy to 2020, which was the main topic of the 6th Croatian Cochrane Symposium (CroCoS), as well as explore prospects for spreading Cochrane activities to Bosnia and Herzegovina (BH), through collaboration with Cochrane Croatia. BH has no officially organized Cochrane activity, as yet. We hope that this article will raise awareness about Cochrane in BH, help promote its activities, and deepen the existing collaboration with Cochrane Croatia. There are already some changes being introduced concerning Cochrane--at least, in one half, the Federation of BH (FBH). Two documents symbolising official recognition of policy changes towards Cochrane have recently been published in the Official Gazette of FBH. Since founding a BH Cochrane Branch would be costly and difficult to achieve in a complicated environment, such as the one we have, BH could use the good will, experience, knowledge, and translated educational, training and web materials of Cochrane Croatia, particularly given the language similarities, to promote evidence based medicine in BH. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  19. New Departure from Nucleate Boiling model relying on first principle energy balance at the boiling surface

    Science.gov (United States)

    Demarly, Etienne; Baglietto, Emilio

    2017-11-01

    Predictions of Departure from Nucleate Boiling have been a longstanding challenge when designing heat exchangers such as boilers or nuclear reactors. Many mechanistic models have been postulated over more than 50 years in order to explain this phenomenon but none is able to predict accurately the conditions which trigger the sudden change of heat transfer mode. This work aims at demonstrating the pertinence of a new approach for detecting DNB by leveraging recent experimental insights. The new model proposed departs from all the previous models by making the DNB inception come from an energy balance instability at the heating surface rather than a hydrodynamic instability of the bubbly layer above the surface (Zuber, 1959). The main idea is to modulate the amount of heat flux being exchanged via the nucleate boiling mechanism by the wetted area fraction on the surface, thus allowing a completely automatic trigger of DNB that doesn't require any parameter prescription. This approach is implemented as a surrogate model in MATLAB in order to validate the principles of the model in a simple and controlled geometry. Good agreement is found with the experimental data leveraged from the MIT Flow Boiling at various flow regimes. Consortium for Advanced Simulation of Light Water Reactors (CASL).

  20. Viroids: from genotype to phenotype just relying on RNA sequence and structural motifs

    Directory of Open Access Journals (Sweden)

    Ricardo eFlores

    2012-06-01

    Full Text Available As a consequence of two unique physical properties, small size and circularity, viroid RNAs do not code for proteins and thus depend on RNA sequence/structural motifs for interacting with host proteins that mediate their invasion, replication, spread, and circumvention of defensive barriers. Viroid genomes fold up on themselves adopting collapsed secondary structures wherein stretches of nucleotides stabilized by Watson-Crick pairs are flanked by apparently unstructured loops. However, compelling data show that they are instead stabilized by alternative non-canonical pairs and that specific loops in the rod-like secondary structure, characteristic of Potato spindle tuber viroid and most other members of the family Pospiviroidae, are critical for replication and systemic trafficking. In contrast, rather than folding into a rod-like secondary structure, most members of the family Avsunvioidae adopt multibranched conformations occasionally stabilized by kissing loop interactions critical for viroid viability in vivo. Besides these most stable secondary structures, viroid RNAs alternatively adopt during replication transient metastable conformations containing elements of local higher-order structure, prominent among which are the hammerhead ribozymes catalyzing a key replicative step in the family Avsunvioidae, and certain conserved hairpins that also mediate replication steps in the family Pospiviroidae. Therefore, different RNA structures ⎯either global or local ⎯ determine different functions, thus highlighting the need for in-depth structural studies on viroid RNAs.

  1. Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention.

    Science.gov (United States)

    Shany-Ur, Tal; Lin, Nancy; Rosen, Howard J; Sollberger, Marc; Miller, Bruce L; Rankin, Katherine P

    2014-08-01

    Accurate self-awareness is essential for adapting one's tasks and goals to one's actual abilities. Patients with neurodegenerative diseases, particularly those with right frontal involvement, often present with poor self-awareness of their functional limitations that may exacerbate their already jeopardized decision-making and behaviour. We studied the structural neuroanatomical basis for impaired self-awareness among patients with neurodegenerative disease and healthy older adults. One hundred and twenty-four participants (78 patients with neurodegenerative diseases including Alzheimer's disease, behavioural variant frontotemporal dementia, right-temporal frontotemporal dementia, semantic variant and non-fluent variant primary progressive aphasia, and 46 healthy controls) described themselves on the Patient Competency Rating Scale, rating observable functioning across four domains (daily living activities, cognitive, emotional control, interpersonal). All participants underwent structural magnetic resonance imaging. Informants also described subjects' functioning on the same scale. Self-awareness was measured by comparing self and informant ratings. Group differences in discrepancy scores were analysed using general linear models, controlling for age, sex and disease severity. Compared with controls, patients with behavioural variant frontotemporal dementia overestimated their functioning in all domains, patients with Alzheimer's disease overestimated cognitive and emotional functioning, patients with right-temporal frontotemporal dementia overestimated interpersonal functioning, and patients with non-fluent aphasia overestimated emotional and interpersonal functioning. Patients with semantic variant aphasia did not overestimate functioning on any domain. To examine the neuroanatomic correlates of impaired self-awareness, discrepancy scores were correlated with brain volume using voxel-based morphometry. To identify the unique neural correlates of overlooking versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one's functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or 'tarnishing' may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or 'polishing' of functional capacity, which appears to be more directly mediated by neural circuit dysfunction. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. A data model for simulation models relying on spatio-temporal urban data

    OpenAIRE

    Langlois , G ,; Tourre , Vincent; Servières , Myriam; Gervais , G ,; Gesquière , Gilles

    2016-01-01

    International audience; To understand the complexity of modern cities and anticipate their expansion, experts from various fields conceive simulation models that can be very different. Those simulation models work with a variety of data with their own organization. Furthermore, because the urban objects are studied in the context of the evolution of a city or urban area, they carry temporal and spatial information. In this paper, we present the base classes of a common data model robust and f...

  3. Defense Headquarters: Geographic Combatant Commands Rely on Subordinate Commands for Mission Management and Execution

    Science.gov (United States)

    2016-06-30

    Committee announced his priorities which included a review of DOD’s organization and lines of authority established as a result of the Goldwater...See enclosure). This report formally transmits an updated briefing and communicates the final results of our work. To describe DOD’s allocation of...its mission to manage the detention facility at Guantanamo Bay, Cuba to Joint Task Force Guantanamo (JTF-GTMO). However, the extent to which each

  4. Relying on fin erosion to identify hatchery-reared brown trout in a Tennessee river

    Science.gov (United States)

    Meerbeek, Jonathan R.; Bettoli, Phillip William

    2012-01-01

    Hatchery-induced fin erosion can be used to identify recently stocked catchable-size brown trout Salmo trutta during annual surveys to qualitatively estimate contributions to a fishery. However, little is known about the longevity of this mark and its effectiveness as a short-term (≤ 1 year) mass-marking technique. We evaluated hatchery-induced pectoral fin erosion as a mass-marking technique for short-term stocking evaluations by stocking microtagged brown trout in a tailwater and repeatedly sampling those fish to observe and measure their pectoral fins. At Dale Hollow National Fish Hatchery, 99.1% (228 of 230) of microtagged brown trout in outdoor concrete raceways had eroded pectoral fins 1 d prior to stocking. Between 34 and 68 microtagged and 26-35 wild brown trout were collected during eight subsequent electrofishing samples. In a blind test based on visual examination of pectoral fins at up to 322 d poststocking, one observer correctly identified 91.7% to 100.0% (mean of 96.9%) of microtagged brown trout prior to checking for microtags. In the laboratory, pectoral fin length and width measurements were recorded to statistically compare the fin measurements of wild and microtagged hatchery brown trout. With only one exception, all pectoral fin measurements on each date averaged significantly larger for wild trout than for microtagged brown trout. Based on the number of pectoral fin measurements falling below 95% prediction intervals, 93.7% (148 of 158) of microtagged trout were correctly identified as hatchery fish based on regression models up to 160 d poststocking. Only 72.2% (70 of 97) of microtagged trout were identified correctly after 160 d based on pectoral fin measurements and the regression models. We concluded that visual examination of pectoral fin erosion was a very effective way to identify stocked brown trout for up to 322 d poststocking.

  5. Urinary concentration does not exclusively rely on plasma vasopressin. A study between genders

    DEFF Research Database (Denmark)

    Graugaard-Jensen, Charlotte; Hvistendahl, Gitte M; Frøkiaer, Jørgen

    2014-01-01

    AimWe investigated the influence of gender on the diurnal regulation of urine production with special focus on vasopressin, oxytocin and prostaglandin E2. MethodsFifteen young women in mid-follicular phase and 22 young men (20-33years) were included. All participants underwent a 24-h circadian in...

  6. To what extent does organic farming rely on nutrient inflows from conventional farming?

    International Nuclear Information System (INIS)

    Nowak, Benjamin; Nesme, Thomas; Pellerin, Sylvain; David, Christophe

    2013-01-01

    Organic farming is increasingly recognized as a prototype for sustainable agriculture. Its guidelines ban the use of artificial fertilizers. However, organic farms may import nutrients from conventional farming through material exchanges. In this study, we aimed at estimating the magnitude of these flows through the quantification of nitrogen, phosphorus and potassium inflows from conventional farming to organic farming. Material inflows and outflows were collected for two cropping years on 63 farms. The farms were located in three French agricultural districts distributed over a gradient of farming activity defined by both the stocking rate and the ratio of the farm area under arable crops. Our results showed that on average, inflows from conventional farming were 23%, 73% and 53% for nitrogen, phosphorus and potassium, respectively. These inflows were strongly determined by the farm production systems. However, for farms similar in terms of production systems, the inflows also depended on the local context, such as the proximity of organic livestock farms: the reliance of organic farming on conventional farming was lower in mixed than in specialized districts. These results highlight the necessity to quantify the contribution of nutrient inflows from conventional farming when assessing organic farming and development scenarios. (letter)

  7. Potential for bias in epidemiologic studies that rely on glass-based retrospective assessment of radon

    International Nuclear Information System (INIS)

    Weinberg, C.R.

    1995-01-01

    Retrospective assessment of exposure to radon remains the greatest challenge in epidemiologic efforts to assess lung cancer risk associated with residential exposure. An innovative technique based on measurement of α-emitting, long-lived daughters embedded by recoil into household glass may one day provide improved radon dosimetry. Particulate air pollution is known, however, to retard the plate-out of radon daughters. This would be expected to result in a differential effect on dosimetry, where the calibration curve relating the actual historical radon exposure to the remaining α-activity in the glass would be different in historically smoky and nonsmoky environments. The resulting open-quotes measurement confoundingclose quotes can distort inferences about the effect of radon and can also produce spurious evidence for synergism between radon exposure and cigarette smoking. 18 refs., 4 figs

  8. Figure-ground segregation can rely on differences in motion direction.

    Science.gov (United States)

    Kandil, Farid I; Fahle, Manfred

    2004-12-01

    If the elements within a figure move synchronously while those in the surround move at a different time, the figure is easily segregated from the surround and thus perceived. Lee and Blake (1999) [Visual form created solely from temporal structure. Science, 284, 1165-1168] demonstrated that this figure-ground separation may be based not only on time differences between motion onsets, but also on the differences between reversals of motion direction. However, Farid and Adelson (2001) [Synchrony does not promote grouping in temporally structured displays. Nature Neuroscience, 4, 875-876] argued that figure-ground segregation in the motion-reversal experiment might have been based on a contrast artefact and concluded that (a)synchrony as such was 'not responsible for the perception of form in these or earlier displays'. Here, we present experiments that avoid contrast artefacts but still produce figure-ground segregation based on purely temporal cues. Our results show that subjects can segregate figure from ground even though being unable to use motion reversals as such. Subjects detect the figure when either (i) motion stops (leading to contrast artefacts), or (ii) motion directions differ between figure and ground. Segregation requires minimum delays of about 15 ms. We argue that whatever the underlying cues and mechanisms, a second stage beyond motion detection is required to globally compare the outputs of local motion detectors and to segregate figure from ground. Since analogous changes take place in both figure and ground in rapid succession, this second stage has to detect the asynchrony with high temporal precision.

  9. Can we rely on predicted basal metabolic rate in chronic pancreatitis outpatients?

    Science.gov (United States)

    Olesen, Søren Schou; Holst, Mette; Køhler, Marianne; Drewes, Asbjørn Mohr; Rasmussen, Henrik Højgaard

    2015-04-01

    Malnutrition is a common complication to chronic pancreatitis (CP) and many patients need nutritional support. An accurate estimation of the basal metabolic rate (BMR) is essential when appropriate nutritional support is to be initiated, but in the clinical settings BMR is cumbersome to measure. We therefore investigated whether BMR can be reliable predicted from a standard formula (the Harris-Benedict equation) in CP outpatients. Twenty-eight patients with clinical stable CP and no current alcohol abuse were enrolled. Patients were stratified according to nutritional risk using the Nutrition Risk Screening 2002 system. Body composition was estimated using bioelectrical impedance. BMR was measured using indirect calorimetry and predicted using the Harris-Benedict equation based on anthropometric data. The average predicted BMR was 1371 ± 216 kcal/day compared to an average measured BMR of 1399 ± 231 kcal/day (P = 0.4). The corresponding limits of agreement were -347 to 290 kcal/day. Twenty-two patients (79%) had a measured BMR between 85 and 115% of the predicted BMR. When analysing patients stratified according to nutritional risk profiles, no differences between predicted and measured BMR were evident for any of the risk profile subgroups (all P > 0.2). The BMR was correlated to fat free mass determined by bioelectrical impedance (rho = 0.55; P = 0.003), while no effect modification was seen from nutritional risk stratification in a linear regression analysis (P = 0.4). The Harris-Benedict equation reliable predicts the measured BMR in four out of five clinical stable CP outpatients with no current alcohol abuse. Copyright © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  10. DIGITAL BOOKS RELY ON SOCIAL READING TO FIND NEW SUCCESS PROPOSALS AND FORMATS

    Directory of Open Access Journals (Sweden)

    Berta García Orosa

    2016-07-01

    Full Text Available Digital reading development has reached turning point. In view of the recent data, the edition of electronic books has dropped for the second consecutive year in 2014, while paper books production has increased (MECD, 2015. The last report from the Fundación Telefónica (2015 points out that six out ten Spanish people prefer printed books instead of the digital ones. This article presents the symptoms of a possible change of tendency in digital books. There is a need for a new digital ecosystem of digital texts production and reception. Its major focus should be the social reading, understood as a space for reception, interpretation, and creation.

  11. Can gingival crevicular blood be relied upon for assessment of blood glucose level?

    Science.gov (United States)

    Dwivedi, Shivani; Verma, Sharmila J; Shah, Monali; Jain, Kapil

    2014-11-01

    Diabetes mellitus (DM) is undiagnosed in approximately half of the patients actually suffering from the disease. In addition, the prevalence of DM is more than twice as high as in patients with periodontitis when compared to periodontally healthy subjects. Thus, a high number of patients with periodontitis may have undiagnosed DM. The purpose of the present study was to evaluate whether blood oozing from a gingival crevice during routine periodontal examination can be used for determining glucose levels. Observational cross-sectional studies were carried out in 75 patients (43 males and 32 females) with chronic periodontitis who were divided into two groups: Group I and Group II, respectively. Blood oozing from the gingival crevices of anterior teeth following periodontal probing was collected with the stick of glucose self-monitoring device, and the blood glucose levels were measured. At the same time, finger-prick blood was taken for glucometric analysis and subsequent readings were recorded. The patient's blood glucose values ranged from 74 to 256 mg/dl. The comparison between gingival crevicular blood and finger-prick blood showed a very strong correlation, with a t value of 3.97 (at P value = 0.001). The data from this study has shown that GCB collected during diagnostic periodontal examination can be an excellent source of blood for glucometric analysis.

  12. The achievement gap: Should we rely on SAT scores to tell us anything about it?

    Directory of Open Access Journals (Sweden)

    Dale Whittington

    2004-04-01

    Full Text Available Increasing numbers of students taking the SAT have declined to identify their race/ethnicity. I examined the impact of non-respondents on the validity of reported racial/ethnic differences and year-to-year changes in test performance. Using an analysis reported by Wainer (1988 and SAT data from 1996 to 2003, I confirmed Wainer’s findings that non-respondents prevent accurate estimations of group differences based on SAT data. I then explored the impact of College Board press release information on news reports about the achievement gap. I found frequent reports of racial/ethnic differences in SAT scores and year-to-year changes in scores but negligible consideration of non-respondents. Press releases and media reports should include information about non-respondents and their impact on accuracy of reported differences based on race/ethnicity.

  13. Communication des risques reliés aux changements climatiques en ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 janv. 2012 ... Il incombe bien sûr aux gouvernements locaux et nationaux de prendre les décisions relatives à l'adaptation aux changements climatiques; ils doivent toutefois les communiquer aux ménages, aux groupes communautaires et aux entreprises privées afin que ceux-ci prennent les décisions qui s'imposent ...

  14. Place preference and vocal learning rely on distinct reinforcers in songbirds.

    Science.gov (United States)

    Murdoch, Don; Chen, Ruidong; Goldberg, Jesse H

    2018-04-30

    In reinforcement learning (RL) agents are typically tasked with maximizing a single objective function such as reward. But it remains poorly understood how agents might pursue distinct objectives at once. In machines, multiobjective RL can be achieved by dividing a single agent into multiple sub-agents, each of which is shaped by agent-specific reinforcement, but it remains unknown if animals adopt this strategy. Here we use songbirds to test if navigation and singing, two behaviors with distinct objectives, can be differentially reinforced. We demonstrate that strobe flashes aversively condition place preference but not song syllables. Brief noise bursts aversively condition song syllables but positively reinforce place preference. Thus distinct behavior-generating systems, or agencies, within a single animal can be shaped by correspondingly distinct reinforcement signals. Our findings suggest that spatially segregated vocal circuits can solve a credit assignment problem associated with multiobjective learning.

  15. Why science? to know, to understand, and to rely on results

    CERN Document Server

    Newton, Roger G

    2012-01-01

    This book aims to describe, for readers uneducated in science, the development of humanity's desire to know and understand the world around us through the various stages of its development to the present, when science is almost universally recognized - at least in the Western world - as the most reliable way of knowing. The book describes the history of the large-scale exploration of the surface of the earth by sea, beginning with the Vikings and the Chinese, and of the unknown interiors of the American and African continents by foot and horseback. After the invention of the telescope, visual exploration of the surfaces of the Moon and Mars were made possible, and finally a visit to the Moon. The book then turns to our legacy from the ancient Greeks of wanting to understand rather than just know, and why the scientific way of understanding is valued. For concreteness, it relates the lives and accomplishments of six great scientists, four from the nineteenth century and two from the twentieth. Finally, the boo...

  16. Short-term Internet search using makes people rely on search engines when facing unknown issues.

    Science.gov (United States)

    Wang, Yifan; Wu, Lingdan; Luo, Liang; Zhang, Yifen; Dong, Guangheng

    2017-01-01

    The Internet search engines, which have powerful search/sort functions and ease of use features, have become an indispensable tool for many individuals. The current study is to test whether the short-term Internet search training can make people more dependent on it. Thirty-one subjects out of forty subjects completed the search training study which included a pre-test, a six-day's training of Internet search, and a post-test. During the pre- and post- tests, subjects were asked to search online the answers to 40 unusual questions, remember the answers and recall them in the scanner. Un-learned questions were randomly presented at the recalling stage in order to elicited search impulse. Comparing to the pre-test, subjects in the post-test reported higher impulse to use search engines to answer un-learned questions. Consistently, subjects showed higher brain activations in dorsolateral prefrontal cortex and anterior cingulate cortex in the post-test than in the pre-test. In addition, there were significant positive correlations self-reported search impulse and brain responses in the frontal areas. The results suggest that a simple six-day's Internet search training can make people dependent on the search tools when facing unknown issues. People are easily dependent on the Internet search engines.

  17. Short-term Internet search using makes people rely on search engines when facing unknown issues.

    Directory of Open Access Journals (Sweden)

    Yifan Wang

    Full Text Available The Internet search engines, which have powerful search/sort functions and ease of use features, have become an indispensable tool for many individuals. The current study is to test whether the short-term Internet search training can make people more dependent on it. Thirty-one subjects out of forty subjects completed the search training study which included a pre-test, a six-day's training of Internet search, and a post-test. During the pre- and post- tests, subjects were asked to search online the answers to 40 unusual questions, remember the answers and recall them in the scanner. Un-learned questions were randomly presented at the recalling stage in order to elicited search impulse. Comparing to the pre-test, subjects in the post-test reported higher impulse to use search engines to answer un-learned questions. Consistently, subjects showed higher brain activations in dorsolateral prefrontal cortex and anterior cingulate cortex in the post-test than in the pre-test. In addition, there were significant positive correlations self-reported search impulse and brain responses in the frontal areas. The results suggest that a simple six-day's Internet search training can make people dependent on the search tools when facing unknown issues. People are easily dependent on the Internet search engines.

  18. Conflict detection and resolution rely on a combination of common and distinct cognitive control networks.

    Science.gov (United States)

    Li, Qi; Yang, Guochun; Li, Zhenghan; Qi, Yanyan; Cole, Michael W; Liu, Xun

    2017-12-01

    Cognitive control can be activated by stimulus-stimulus (S-S) and stimulus-response (S-R) conflicts. However, whether cognitive control is domain-general or domain-specific remains unclear. To deepen the understanding of the functional organization of cognitive control networks, we conducted activation likelihood estimation (ALE) from 111 neuroimaging studies to examine brain activation in conflict-related tasks. We observed that fronto-parietal and cingulo-opercular networks were commonly engaged by S-S and S-R conflicts, showing a domain-general pattern. In addition, S-S conflicts specifically activated distinct brain regions to a greater degree. These regions were implicated in the processing of the semantic-relevant attribute, including the inferior frontal cortex (IFC), superior parietal cortex (SPC), superior occipital cortex (SOC), and right anterior cingulate cortex (ACC). By contrast, S-R conflicts specifically activated the left thalamus, middle frontal cortex (MFC), and right SPC, which were associated with detecting response conflict and orienting spatial attention. These findings suggest that conflict detection and resolution involve a combination of domain-general and domain-specific cognitive control mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. JET ({sup 3}He)-D scenarios relying on RF heating: survey of selected recent experiments

    Energy Technology Data Exchange (ETDEWEB)

    Van Eester, D; Lerche, E; Andrew, Y; Biewer, T M; Casati, A; Crombe, K; De la Luna, E; Ericsson, G; Felton, R; Giacomelli, L; Giroud, C; Hawkes, N; Hellesen, C; Hjalmarsson, A; Joffrin, E; Kaellne, J; Kiptily, V; Lomas, P; Mantica, P; Marinoni, A [JET-EFDA Culham Science Centre, Abingdon, OX14 3DB (United Kingdom)] (and others)

    2009-04-15

    Recent JET experiments have been devoted to the study of ({sup 3}He)-D plasmas involving radio frequency (RF) heating. This paper starts by discussing the RF heating efficiency theoretically expected in such plasmas, covering both relevant aspects of wave and of particle dynamics. Then it gives a concise summary of the main conclusions drawn from recent experiments that were either focusing on studying RF heating physics aspects or that were adopting RF heating as a tool to study plasma behavior. Depending on the minority concentration chosen, different physical phenomena are observed. At very low concentration (X[{sup 3}He] < 1%), energetic tails are formed which trigger MHD activity and result in loss of fast particles. Alfven cascades were observed and gamma ray tomography indirectly shows the impact of sawtooth crashes on the fast particle orbits. Low concentration (X[{sup 3}He] < 10%) favors minority heating while for X[{sup 3}He] >> 10% electron mode conversion damping becomes dominant. Evidence for the Fuchs et al standing wave effect (Fuchs et al 1995 Phys. Plasmas 2 1637-47) on the absorption is presented. RF induced deuterium tails were observed in mode conversion experiments with large X[{sup 3}He] ({approx}18%). As tentative modeling shows, the formation of these tails can be explained as a consequence of wave power absorption by neutral beam particles that efficiently interact with the waves well away from the cold D cyclotron resonance position as a result of their substantial Doppler shift. As both ion and electron RF power deposition profiles in ({sup 3}He)-D plasmas are fairly narrow-giving rise to localized heat sources-the RF heating method is an ideal tool for performing transport studies. Various of the experiments discussed here were done in plasmas with internal transport barriers (ITBs). ITBs are identified as regions with locally reduced diffusivity, where poloidal spinning up of the plasma is observed. The present know-how on the role of RF heating for impurity transport is also briefly summarized.

  20. CERN birthplace of the World Wide Web relies on Day's Communiqué

    CERN Multimedia

    2001-01-01

    In close collaboration with CERN, Day developed a platform to enable interested research groups to integrate disparate data sources and to author content based on individual needs... Days Virtual Repository - The ContentBus - allows the integration of data sources and provides for the presentation of all work processes at CERN, from pure text to complex research data. With data procured in real time from the original location, it avoids data redundancy, insufficient scalability and unneccessary allocation of resources for constant data reconcilliation and additional database licenses.

  1. Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

    Science.gov (United States)

    Keriel, Anne; Botella, Eric; Estrach, Soline; Bragagnolo, Gabriel; Vergunst, Annette C; Feral, Chloe C; O'Callaghan, David

    2015-06-01

    Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Efficient peroxydisulfate activation process not relying on sulfate radical generation for water pollutant degradation.

    Science.gov (United States)

    Zhang, Tao; Chen, Yin; Wang, Yuru; Le Roux, Julien; Yang, Yang; Croué, Jean-Philippe

    2014-05-20

    Peroxydisulfate (PDS) is an appealing oxidant for contaminated groundwater and toxic industrial wastewaters. Activation of PDS is necessary for application because of its low reactivity. Present activation processes always generate sulfate radicals as actual oxidants which unselectively oxidize organics and halide anions reducing oxidation capacity of PDS and producing toxic halogenated products. Here we report that copper oxide (CuO) can efficiently activate PDS under mild conditions without producing sulfate radicals. The PDS/CuO coupled process is most efficient at neutral pH for decomposing a model compound, 2,4-dichlorophenol (2,4-DCP). In a continuous-flow reaction with an empty-bed contact time of 0.55 min, over 90% of 2,4-DCP (initially 20 μM) and 90% of adsorbable organic chlorine (AOCl) can be removed at the PDS/2,4-DCP molar ratio of 1 and 4, respectively. Based on kinetic study and surface characterization, PDS is proposed to be first activated by CuO through outer-sphere interaction, the rate-limiting step, followed by a rapid reaction with 2,4-DCP present in the solution. In the presence of ubiquitous chloride ions in groundwater/industrial wastewater, the PDS/CuO oxidation shows significant advantages over sulfate radical oxidation by achieving much higher 2,4-DCP degradation capacity and avoiding the formation of highly chlorinated degradation products. This work provides a new way of PDS activation for contaminant removal.

  3. refining of scintillation detector signals relying on interpolated wavelets on a FPGA prototype

    International Nuclear Information System (INIS)

    Aboshosha, A.; Sayed, M.; Ashour, M.; Safwat, A.

    2010-01-01

    in this article, a signal processing core based on field programmable gate arrays (FPGAs) is developed for processing of scintillation detector signals. this core is implemented to apply the forward wavelet transfrom and interpolation technique. the main purpose of that is to de-noise, compress and reconstruct these signals by which the processing speed and storage will be optimized. moreover, this technique gives us all important features of the acquired signals such as counting, shaping and pulse height. A new contribution of our framework arises from employing the interpolation techniques to reconstruct the signal where the mother wavelet and details are not required. The hardware design is implemented using hardware description language (HDL) and is implemented practically on the FPGA. The performance of the design has been tested in simulation mode on Model sim benchmark and in real time mode on XC2S 50 spartan- II FPGA.

  4. Ants learn to rely on more informative attributes during decision-making.

    Science.gov (United States)

    Sasaki, Takao; Pratt, Stephen C

    2013-01-01

    Evolutionary theory predicts that animals act to maximize their fitness when choosing among a set of options, such as what to eat or where to live. Making the best choice is challenging when options vary in multiple attributes, and animals have evolved a variety of heuristics to simplify the task. Many of these involve ranking or weighting attributes according to their importance. Because the importance of attributes can vary across time and place, animals might benefit by adjusting weights accordingly. Here, we show that colonies of the ant Temnothorax rugatulus use their experience during nest site selection to increase weights on more informative nest attributes. These ants choose their rock crevice nests on the basis of multiple features. After exposure to an environment where only one attribute differentiated options, colonies increased their reliance on this attribute relative to a second attribute. Although many species show experience-based changes in selectivity based on a single feature, this is the first evidence in animals for adaptive changes in the weighting of multiple attributes. These results show that animal collectives, like individuals, change decision-making strategies according to experience. We discuss how these colony-level changes might emerge from individual behaviour.

  5. Early Career Researchers Demand Full-text and Rely on Google to Find Scholarly Sources

    Directory of Open Access Journals (Sweden)

    Richard Hayman

    2017-12-01

    Full Text Available A Review of: Nicholas, D., Boukacem-Zeghmouri, C., Rodríguez-Bravo, B., Xu, J., Watkinson, A., Abrizah, A., Herman, E., & Świgoń, M. (2017. Where and how early career researchers find scholarly information. Learned Publishing, 30(1, 19-29. http://dx.doi.org/10.1002/leap.1087 Abstract Objective – To examine the attitudes and information behaviours of early career researchers (ECRs when locating scholarly information. Design – Qualitative longitudinal study. Setting – Research participants from the United Kingdom, United States of America, China, France, Malaysia, Poland, and Spain. Subjects – A total 116 participants from various disciplines, aged 35 and younger, who were holding or had previously held a research position, but not in a tenured position. All participants held a doctorate or were in the process of earning one. Methods – Using structured interviews of 60-90 minutes, researchers asked 60 questions of each participant via face-to-face, Skype, or telephone interviews. The interview format and questions were formed via focus groups. Main Results – As part of a longitudinal project, results reported are limited to the first year of the study, and focused on three primary questions identified by the authors: where do ECRs find scholarly information, whether they use their smartphones to locate and read scholarly information, and what social media do they use to find scholarly information. Researchers describe how ECRs themselves interpreted the phrase scholarly information to primarily mean journal articles, while the researchers themselves had a much expanded definition to include professional and “scholarly contacts, ideas, and data” (p. 22. This research shows that Google and Google Scholar are widely used by ECRs for locating scholarly information regardless of discipline, language, or geography. Their analysis by country points to currency and the combined breadth-and-depth search experience that Google provides as prime reasons for the popularity of Google and Google Scholar. Of particular interest is the popularity and use of Google Scholar in China, where it is officially blocked but accessed by ECRs via proxy services. Other general indexes, such as Web of Science and Scopus, are also popular but not universally used by ECRs, and regional differences again point to pros and cons of these services. Some specialized services are emphasized, including regional tools such as the China National Knowledge Infrastructure, as well as certain broad disciplinary resources, such as PubMed for its coverage of sciences and biomedical information. Researchers report that ECRs participating in this study were less concerned about how they gained access to full-text scholarly information, only that they could access full-text sources. In particular, ECRs do not take much notice of libraries and their platforms, seemingly unaware of the steps libraries take to acquire and ensure access to scholarly information, while viewing physical libraries themselves primarily as study spaces for undergraduate students and not places for the ECR to visit or work. While ECRs occasionally acknowledge library portals and login interfaces, researchers found that these participants mostly ignored these, and that they found discovery services to be confusing or difficult. Concerning social media use, participants identified 11 different platforms used but only ResearchGate was mentioned and used by participants from all seven countries represented. Social media tends to be used directly for keeping track of research trends and opinions and also the work specific researchers are publishing, and indirectly when referred to sites such as ResearchGate to find full-text of a specific article. Facebook, Twitter, and LinkedIn are used occasionally or moderately, but not universally. Researchers highlight regional differences of social media use in China, where ECRs are more likely to connect with other researchers and receive notifications when those researchers publish. The study reports limited information ECRs’ use of smartphones for information seeking. About half of ECR participants reported use of their smartphone for discovering scholarly sources. The advantage smartphones provide includes near-ubiquitous Internet access and therefore the ability to access scholarly materials on the go, though ECRs are less likely to download or read full-text articles via their smartphones. The rate of adoption of smartphone use for scholarly materials varies by country. Conclusion – Early career researchers access scholarly information in a wide variety of ways, with Google and Google Scholar as the preferred starting location, and with social media also proving useful. Ease-of-use and full-text availability are paramount concerns; the spread of open access materials helps fuel the availability of materials, and Google makes these easy to find. Though physical libraries are perceived to be of limited use, the digital access they provide to full-text scholarly sources is still vital even if ECRs do not make the connection between having that important access and the fact that libraries act as buyers and providers of access

  6. Antropogenní transformace reliéfu v oblasti dolu Jeroným

    Czech Academy of Sciences Publication Activity Database

    Kirchner, Karel; Roštínský, Pavel

    2011-01-01

    Roč. 18, č. 1 (2011), s. 92-98 ISSN 1803-1447 R&D Projects: GA ČR GA105/09/0089 Institutional research plan: CEZ:AV0Z30860518 Keywords : geomorphology * anthropogenic transformation * Slavkovský les Forest Subject RIV: DE - Earth Magnetism, Geodesy, Geography www.caag.cz

  7. Neuroprotective effects of 17β-estradiol rely on estrogen receptor membrane initiated signals

    Directory of Open Access Journals (Sweden)

    Marco eFiocchetti

    2012-04-01

    Full Text Available 17β-estradiol (E2 exerts protective effects in the central nervous system besides its crucial role in many physiological and pathological events. E2 effects are not restricted to the brain areas related with the control of the reproductive function, but rather are widespread throughout the developing and the adult brain. E2 actions are mediated by estrogen receptors (i.e., ERα and ERβ belonging to the nuclear receptor super family. As members of the ligand-regulated transcription factor family, the actions of ERs in the brain were thought to mediate only the E2 long-term transcriptional effects. However, a growing body of evidence has emerged indicating the presence of rapid, membrane initiated E2 effects in the brain which result independent from ER transcriptional activities and involved in E2-induced neuroprotection. Aim of this review is to focus on the rapid effects of E2 in the brain taking into account the specific contribution of the signaling pathway of ERβ subtype in neuroprotective actions of E2.

  8. Skipping of Chinese characters does not rely on word-based processing.

    Science.gov (United States)

    Lin, Nan; Angele, Bernhard; Hua, Huimin; Shen, Wei; Zhou, Junyi; Li, Xingshan

    2018-02-01

    Previous eye-movement studies have indicated that people tend to skip extremely high-frequency words in sentence reading, such as "the" in English and "/de" in Chinese. Two alternative hypotheses have been proposed to explain how this frequent skipping happens in Chinese reading: one assumes that skipping happens when the preview has been fully identified at the word level (word-based skipping); the other assumes that skipping happens whenever the preview character is easy to identify regardless of whether lexical processing has been completed or not (character-based skipping). Using the gaze-contingent display change paradigm, we examined the two hypotheses by substituting the preview of the third character of a four-character Chinese word with the high-frequency Chinese character "/de", which should disrupt the ongoing word-level processing. The character-based skipping hypothesis predicts that this manipulation will enhance the skipping probability of the target character (i.e., the third character of the target word), because the character "/de" has much higher character frequency than the original character. The word-based skipping hypothesis instead predicts a reduction of the skipping probability of the target character because the presence of the character "/de" is lexically infelicitous at word level. The results supported the character-based skipping hypothesis, indicating that in Chinese reading the decision of skipping a character can be made before integrating it into a word.

  9. Efficient peroxydisulfate activation process not relying on sulfate radical generation for water pollutant degradation

    KAUST Repository

    Zhang, Tao

    2014-05-20

    Peroxydisulfate (PDS) is an appealing oxidant for contaminated groundwater and toxic industrial wastewaters. Activation of PDS is necessary for application because of its low reactivity. Present activation processes always generate sulfate radicals as actual oxidants which unselectively oxidize organics and halide anions reducing oxidation capacity of PDS and producing toxic halogenated products. Here we report that copper oxide (CuO) can efficiently activate PDS under mild conditions without producing sulfate radicals. The PDS/CuO coupled process is most efficient at neutral pH for decomposing a model compound, 2,4-dichlorophenol (2,4-DCP). In a continuous-flow reaction with an empty-bed contact time of 0.55 min, over 90% of 2,4-DCP (initially 20 μM) and 90% of adsorbable organic chlorine (AOCl) can be removed at the PDS/2,4-DCP molar ratio of 1 and 4, respectively. Based on kinetic study and surface characterization, PDS is proposed to be first activated by CuO through outer-sphere interaction, the rate-limiting step, followed by a rapid reaction with 2,4-DCP present in the solution. In the presence of ubiquitous chloride ions in groundwater/industrial wastewater, the PDS/CuO oxidation shows significant advantages over sulfate radical oxidation by achieving much higher 2,4-DCP degradation capacity and avoiding the formation of highly chlorinated degradation products. This work provides a new way of PDS activation for contaminant removal. © 2014 American Chemical Society.

  10. PERiMENSTRUAL DiSTRES VE HEMiŞiRELiK YAKLAŞIMI

    OpenAIRE

    KIZILKAYA, Nezihe

    2015-01-01

    Kadm populasyonunun % 70'inden \\'Ogu perimenstrual distres §ikayetlerinin en az bir ya da daha fazlasmdan etkilenmektedir. Perimenstrual distres  §ikayetlerinin azaltihnas1 ya da Onlen1nesi iyin stres azalt1na, egzersiz, diyet, egiti1n ve da.n1 rnanhk bile§enlerinden olu§an <;ok boyutlu bio-psiko-sosyal bir yakla§1m oneril mektedir. Hem§ireler perimenstrual distres §ikayetlerinin onlenmesi ya da tedavisinde <;ok onemli bir role sahiptirler.

  11. Metabolic imidacloprid resistance in the brown planthopper, Nilaparvata lugens, relies on multiple P450 enzymes.

    Science.gov (United States)

    Zhang, Yixi; Yang, Yuanxue; Sun, Huahua; Liu, Zewen

    2016-12-01

    Target insensitivity contributing to imidacloprid resistance in Nilaparvata lugens has been reported to occur either through point mutations or quantitative change in nicotinic acetylcholine receptors (nAChRs). However, the metabolic resistance, especially the enhanced detoxification by P450 enzymes, is the major mechanism in fields. From one field-originated N. lugens population, an imidacloprid resistant strain G25 and a susceptible counterpart S25 were obtained to analyze putative roles of P450s in imidacloprid resistance. Compared to S25, over-expression of twelve P450 genes was observed in G25, with ratios above 5.0-fold for CYP6AY1, CYP6ER1, CYP6CS1, CYP6CW1, CYP4CE1 and CYP425B1. RNAi against these genes in vivo and recombinant tests on the corresponding proteins in vitro revealed that four P450s, CYP6AY1, CYP6ER1, CYP4CE1 and CYP6CW1, played important roles in imidacloprid resistance. The importance of the four P450s was not equal at different stages of resistance development based on their over-expression levels, among which CYP6ER1 was important at all stages, and that the others might only contribute at certain stages. The results indicated that, to completely reflect roles of P450s in insecticide resistances, their over-expression in resistant individuals, expression changes at the stages of resistance development, and catalytic activities against insecticides should be considered. In this study, multiple P450s, CYP6AY1, CYP6ER1, CYP4CE1 and CYP6CW1, have proven to be important in imidacloprid resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Atmea launches Atmea1 the mid-sized generation 3+ PWR you can rely on

    International Nuclear Information System (INIS)

    2008-01-01

    ATMEA, a daughter company of AREVA NP and Mitsubishi Heavy Industries, is developing and will supply ATMEA1, the most advanced 1100 MWe PWR plant with the combination of the unique set of competence and experience of its parent companies. This folder presents the ATMEA1 reactor main features. (J.S.)

  13. Property Mix Heterogeneity and Market Cycles: How Much Can We Rely on Median-Price Indices?

    Directory of Open Access Journals (Sweden)

    Odilon Ricardo da Hora Gonçalves Fernandes Costa

    2017-05-01

    Full Text Available Objective. Understand in which types of location median-price indices could provide reasonable estimates of rent growth. As far as our research allows, the market-based measures developed througout this study are the first to emphasize office properties in Brazil using an hedonic framework.Methodology. Create appraisal-based indices of rent growth using median-price and hedonic-based techniques for two regions with different degrees of property mix heterogeneity and compare their behavior overtime.Findings. Volatility in median-price measures is larger than hedonic-based measures in market peaks and throughs due to different weighting of high and low-tier properties overtime. This result is stronger in the location with higher property mix heterogeneity and, consequently, exacerbates market cycles in this region.  Limitations. We do not find statistically significant differences between the measures considered. Nevertheless, we do not consider whether this similarity would hold when using transactional-based data.    Value. Our results suggest that researchers, policy makers and investors need to take into account the “undesired fluctuation” of median-price measures when interpreting such indices.  

  14. Nature does not rely on long-lived electronic quantum coherence for photosynthetic energy transfer

    Science.gov (United States)

    Duan, Hong-Guang; Prokhorenko, Valentyn I.; Cogdell, Richard J.; Ashraf, Khuram; Stevens, Amy L.; Thorwart, Michael; Miller, R. J. Dwayne

    2017-08-01

    During the first steps of photosynthesis, the energy of impinging solar photons is transformed into electronic excitation energy of the light-harvesting biomolecular complexes. The subsequent energy transfer to the reaction center is commonly rationalized in terms of excitons moving on a grid of biomolecular chromophores on typical timescales Olson protein, in which interference oscillatory signals up to 1.5 ps were reported and interpreted as direct evidence of exceptionally long-lived electronic quantum coherence. Here, we show that the optical 2D photon echo spectra of this complex at ambient temperature in aqueous solution do not provide evidence of any long-lived electronic quantum coherence, but confirm the orthodox view of rapidly decaying electronic quantum coherence on a timescale of 60 fs. Our results can be considered as generic and give no hint that electronic quantum coherence plays any biofunctional role in real photoactive biomolecular complexes. Because in this structurally well-defined protein the distances between bacteriochlorophylls are comparable to those of other light-harvesting complexes, we anticipate that this finding is general and directly applies to even larger photoactive biomolecular complexes.

  15. You can’t rely on color, yet we all do 2.0 (Manuscript only)

    NARCIS (Netherlands)

    Nes, van F.L.; Eschbach, R.; Marcu, G.G.; Rizzi, A.

    2013-01-01

    Everybody views and uses color from early childhood onwards. But this magnificent property of all objects around us turns out to be elusive if you try to specify it and communicate it to another person. Also, people often don’t know what effects color may have under different conditions. However,

  16. SEE ME ROAR: Self-determination Enhanced Engagement for Math Education Relying On Augmented Reality

    NARCIS (Netherlands)

    Li, J.; van der Spek, E.D.; Hu, J.; Feijs, L.M.G.

    2017-01-01

    Contemporary primary school students generally spend a lot of time playing digital games, but may be less interested in their schoolwork, such as learning mathematics. Mathematics includes many abstract concepts that can be difficult to grasp for some students. Augmented reality as a technology

  17. Early Career Researchers Demand Full-text and Rely on Google to Find Scholarly Sources

    OpenAIRE

    Richard Hayman

    2017-01-01

    A Review of: Nicholas, D., Boukacem-Zeghmouri, C., Rodríguez-Bravo, B., Xu, J., Watkinson, A., Abrizah, A., Herman, E., & Świgoń, M. (2017). Where and how early career researchers find scholarly information. Learned Publishing, 30(1), 19-29. http://dx.doi.org/10.1002/leap.1087 Abstract Objective – To examine the attitudes and information behaviours of early career researchers (ECRs) when locating scholarly information. Design – Qualitative longitudinal study. Setting – R...

  18. Efficient peroxydisulfate activation process not relying on sulfate radical generation for water pollutant degradation

    KAUST Repository

    Zhang, Tao; Chen, Yin; Wang, Yuru; Le Roux, Julien; Yang, Yang; Croue, Jean-Philippe

    2014-01-01

    Peroxydisulfate (PDS) is an appealing oxidant for contaminated groundwater and toxic industrial wastewaters. Activation of PDS is necessary for application because of its low reactivity. Present activation processes always generate sulfate radicals

  19. Wild hummingbirds rely on landmarks not geometry when learning an array of flowers.

    Science.gov (United States)

    Hurly, T Andrew; Fox, Thomas A O; Zwueste, Danielle M; Healy, Susan D

    2014-09-01

    Rats, birds or fish trained to find a reward in one corner of a small enclosure tend to learn the location of the reward using both nearby visual features and the geometric relationships of corners and walls. Because these studies are conducted under laboratory and thereby unnatural conditions, we sought to determine whether wild, free-living rufous hummingbirds (Selasphorus rufus) learning a single reward location within a rectangular array of flowers would similarly employ both nearby visual landmarks and the geometric relationships of the array. Once subjects had learned the location of the reward, we used test probes in which one or two experimental landmarks were moved or removed in order to reveal how the birds remembered the reward location. The hummingbirds showed no evidence that they used the geometry of the rectangular array of flowers to remember the reward. Rather, they used our experimental landmarks, and possibly nearby, natural landmarks, to orient and navigate to the reward. We believe this to be the first test of the use of rectangular geometry by wild animals, and we recommend further studies be conducted in ecologically relevant conditions in order to help determine how and when animals form complex geometric representations of their local environments.

  20. Mask induction despite circuit obstruction: an unrecognized hazard of relying on automated machine check technology.

    Science.gov (United States)

    Yang, Kamie K; Lewis, Ian H

    2014-06-15

    Various equipment malfunctions of anesthesia gas delivery systems have been previously reported. Our profession increasingly uses technology as a means to prevent these errors. We report a case of a near-total anesthesia circuit obstruction that went undetected before the induction of anesthesia despite the use of automated machine check technology. This case highlights that automated machine check modules can fail to detect severe equipment failure and demonstrates how, even in this era of expanding technology, manual checks still remain essential components of safe care.

  1. The assessment of nanofluid in a Von Karman flow with temperature relied viscosity

    Directory of Open Access Journals (Sweden)

    Anum Tanveer

    2018-06-01

    Full Text Available This work endeavor to study the heat and mass transfer viscous nanofluid features in a Von Karman flow invoking the variable viscosity mechanism. Moreover, we have extended our study in view of heat generation and uniform suction effects. The flow triggering non-linear partial differential equations are inscribed in the non-dimensional form by manipulating suitable transformations. The resulting non-linear ordinary differential equations are solved numerically via implicit finite difference scheme in conjecture with the Newton’s linearization scheme afterwards. The sought solutions are plotted graphically to present comparison between MATLAB routine bvp4c and implicit finite difference schemes. Impact of different parameters on the concentration/temperature/velocity profiles are highlighted. Further Nusselt number, skin friction and Sherwood number characteristics are discussed for better exposition. Keywords: Von Karman flow, Variable viscosity, Heat generation, Suction, Nanofluid, Implicit finite difference scheme, Bvp4c

  2. Leprosy and the adaptation of human toll-like receptor 1.

    Directory of Open Access Journals (Sweden)

    Sunny H Wong

    2010-07-01

    Full Text Available Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8, OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14, OR = 0.43, 95% CI = 0.35-0.54. The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

  3. Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family.

    Science.gov (United States)

    Akoğlu, Gülşen; Metin, Ahmet; Ceylan, Gülay Güleç; Emre, Selma; Akpolat, Demet; Süngü, Nuran

    2015-02-01

    Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH. © 2014 The International Society of Dermatology.

  4. Autoimmune hepatitis in Italy: the Bologna experience.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Quarneti, Chiara; Ferri, Silvia; Menichella, Rita; Cassani, Fabio; Pappas, Georgios; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

    2009-06-01

    Autoimmune hepatitis affects mainly women. It is subdivided into type 1 and type 2 according to the autoantibody profile and without immunosuppression usually evolves to cirrhosis and end-stage liver failure. We evaluated clinical, biochemical, immunological and genetic features and treatment response of 163 consecutive Italian patients with autoimmune hepatitis. At diagnosis, type 1 autoimmune hepatitis showed more inflamed liver histology and more pronounced cholestasis, whereas type 2 was more common in children. Male and female patients shared similar clinical, biochemical and immunological features. Of 89 patients with 5-year follow-up or longer, 23 patients irrespective of presenting clinical, biochemical and immunological features achieved complete remission (normal transaminases and gammaglobulin levels) which was maintained with minimal steroid dosage; attempt at treatment withdrawal led to disease exacerbation. Complete responders had more often HLA DRB1*0401 (p = 0.011) and their risk of disease progression was lower (p < 0.0001). Type 1 and type 2 autoimmune hepatitis is one and the same disease. Autoimmune hepatitis has similar features in male and female patients. HLA DRB1*0401 positive patients are more likely to achieve complete remission. Continuous low-dose steroids are necessary to maintain remission, significantly reducing the risk of disease progression.

  5. Genetic Mutation and Exosome Signature of Human Papilloma Virus Associated Oropharyngeal Cancer

    Science.gov (United States)

    Kannan, Anbarasu; Hertweck, Kate L.; Philley, Julie V.; Wells, Robert B.; Dasgupta, Santanu

    2017-01-01

    Human papilloma virus-16 (HPV-16) associated oropharyngeal cancer (HPVOPC) is increasing alarmingly in the United States. We performed whole genome sequencing of a 44 year old, male HPVOPC subject diagnosed with moderately differentiated tonsillar carcinoma. We identified new somatic mutation in MUC16 (A.k.a. CA-125), MUC12, MUC4, MUC6, MUC2, SIRPA, HLA-DRB1, HLA-A and HLA-B molecules. Increased protein expression of MUC16, SIRPA and decreased expression of HLA-DRB1 was further demonstrated in this HPVOPC subject and an additional set of 15 HPVOPC cases. Copy number gain (3 copies) was also observed for MUC2, MUC4, MUC6 and SIRPA. Enhanced expression of MUC16, SIRPA and HPV-16-E7 protein was detectable in the circulating exosomes of numerous HPVOPC subjects. Treatment of non-tumorigenic mammary epithelial cells with exosomes derived from aggressive HPVOPC cells harboring MUC16, SIRPA and HPV-16-E7 proteins augmented invasion and induced epithelial to mesenchymal transition (EMT) accompanied by an increased expression ratio of the EMT markers Vimentin/E-cadherin. Exosome based screening of key HPVOPC associated molecules could be beneficial for early cancer diagnosis, monitoring and surveillance. PMID:28383029

  6. Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

    Science.gov (United States)

    Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

    2010-11-01

    Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

  7. Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

    Science.gov (United States)

    Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

    2017-06-01

    Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

  8. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  9. HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction.

    Science.gov (United States)

    Walton, D C; Hiho, S J; Cantwell, L S; Diviney, M B; Wright, S T; Snell, G I; Paraskeva, M A; Westall, G P

    2016-09-01

    Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. Exceptional manifestation of polyautoimmunity in a very young girl – a case report

    Directory of Open Access Journals (Sweden)

    Agnieszka Mroczkowska-Juchkiewicz

    2017-05-01

    Full Text Available Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. The exact pathogenic mechanisms responsible for the coexistence of distinct autoimmune diseases within an individual have not been clearly explained. We report a case of a very young girl with the extremely rare co-existence of four distinct autoimmune diseases i.e. juvenile idiopathic arthritis, type 1 diabetes mellitus, coeliac disease and autoimmune hepatitis, recognized based on validated international classification criteria. The best to our knowledge there has been no case reporting coexistence of these particular four disorders in an individual. Moreover, all these diseases occurred during first three years of life, which also cause that case unique. Molecular studies of human leukocyte antigen (HLA class II in our patient showed the presence of the HLA DRB1*01, HLA DRB1*03, HLA DQB1*02, HLA DQB1*05 molecules, which may suggest immunogenetic links between those autoimmune diseases. The presented case highlights the importance of active screening for other autoimmune diseases, if a patient with one autoimmune disease manifests with new or nonspecific symptoms.

  11. The constructive process in the Cimorro zone in the the Cathedral of Avila, (century XII-XIV. Hypothesis and its verification through the analysis of Structural Stability Smart and Sustainable Offices (SSO

    Directory of Open Access Journals (Sweden)

    Mª A. Benito Pradillo

    2018-01-01

    Full Text Available This paper presents a hypothesis about the order in the constructive process for the head zone in the Cathedral of Ávila, called Cimorro. The hypothesis proposed in this area considers for its construction three different stages: XII Century, XIII Century and XIV Century. The proposed hypotesis have been verified with the Analysis of Stability realised. The theoretical Framework used is the Limit Analysis to Masonry Structures. After prooving the Structural Stability for each of the building stages, the following conclusions are made: Through the XII Century, the possibility of closing the central vault without Buttress System for a short period of time and the subsequent placement of a tribune is stated. A fortification formed by the barbican and the «adarves» were built during the XIII Century. In the XIV Century, the tribune is removed and replaced with the Buttress System with buttress and double flying buttress, which we can see nowadays.

  12. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  13. The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype

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    Christina Reinauer

    2017-05-01

    Full Text Available Introduction: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA DR and DQ haplotypes in a cohort with early-onset (age < 5 years, long term type 1 diabetes (T1D and explored their influence on clinical and laboratory parameters. Methods: Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. Results: Genetic variability was low, 44.6% (104/233 of early-onset T1D patients carried the highest-risk genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05, and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n = 83, moderate (n = 106 and low risk (n = 6 genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years, metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (each p > 0.05. Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. Conclusion: In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation.

  14. HLA –DRB1*, DQB1* Alleles In Hydatid Patients By Molecular Typing

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    mehdi Mosayebi

    2007-10-01

    Full Text Available Mosayebi M1, Dalimi Asl A2, Moazeni M3, Mosayebi Gh4 1. Ph.D Student, Department of Parasitology, Faculty of medicine, Tarbiat Modarres University 2. Professor, Department of Parasitology, Faculty of medicine, Tarbiat Modarres University 3. Professor, Department of Immunology, Faculty of medicine, Tarbiat Modarres University 4. Assistant professor, Department of Immunology, Faculty of medicine, Arak Medical Sciences University Abstract Background: Hydatidosis is a important disease that results from infection with larvae of the dog tape worm , Echinococcus granulosus in human and farm animals .Resistance or susceptibility to infectious diseases , for example , cystic and alveolar echinococcosis is restricted by individual host factors and immunologic responses,in many surveys has been shown.The target of this study that is the first survey dealing with the correlation between HLA-DRB1*& DQB1* alleles and cystic echinococcosis in Iranian patient,is investigation HLA-DRB1*and DQB1* allelic polymorphism in Iranian patient with hydatidosis . Materials and methods: The study was carried out on 56 patients with confirmed cystic echinococcosis and 30 apparently healthy individuals living on Arak area by HLA-DRB1*& DQB1* typing with PCR-SSP method.The first step was founding patients and blood sampling .DNA was prepared from whole blood and we used PCR-SSP with 31 primer mixes for per sample . PCR reaction mixtures were loaded in agarose gels and after electrophoresis , geles were examine under UV illumination and gel document . Analyse of results carried out with specific software and frequency& interpretation tables and homogeneity test for calculation of P-value in χ2 test with fisher΄s exact test . significant samples with logistic regression analysed and Odds-ratio calculate . Results: A statistically significant positive association was found between HLA-DQB1*02 and the occurrence of cystic echinococcosis(P<0.05,(Odds-ratio=2.87 Conclusion: The

  15. Clinical and Genetic Characteristics of Non-Insulin-Requiring Glutamic Acid Decarboxylase (GAD Autoantibody-Positive Diabetes: A Nationwide Survey in Japan.

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    Junichi Yasui

    Full Text Available Glutamic acid decarboxylase autoantibodies (GADAb differentiate slowly progressive insulin-dependent (type 1 diabetes mellitus (SPIDDM from phenotypic type 2 diabetes, but many GADAb-positive patients with diabetes do not progress to insulin-requiring diabetes. To characterize GADAb-positive patients with adult-onset diabetes who do not require insulin therapy for >5 years (NIR-SPIDDM, we conducted a nationwide cross-sectional survey in Japan.We collected 82 GADAb-positive patients who did not require insulin therapy for >5 years (NIR-SPIDDM and compared them with 63 patients with insulin-requiring SPIDDM (IR-SPIDDM. Clinical and biochemical characteristics, HLA-DRB1-DQB1 haplotypes, and predictive markers for progression to insulin therapy were investigated.Compared with the IR-SPIDDM group, the NIR-SPIDDM patients showed later diabetes onset, higher body mass index, longer duration before diagnosis, and less frequent hyperglycemic symptoms at onset. In addition, C-peptide, LDL-cholesterol, and TG were significantly higher in the NIR-SPIDDM compared to IR-SPIDDM patients. The NIR-SPIDDM group had lower frequency of susceptible HLA-DRB1*04:05-DQB1*04:01 and a higher frequency of resistant HLA-DRB1*15:01-DQB1*06:02 haplotype compared to IR-SPIDDM. A multivariable analysis showed that age at diabetes onset (OR = 0.82, duration before diagnosis of GADAb-positive diabetes (OR = 0.82, higher GADAb level (≥10.0 U/ml (OR = 20.41, and fasting C-peptide at diagnosis (OR = 0.07 were independent predictive markers for progression to insulin-requiring diabetes. An ROC curve analysis showed that the optimal cut-off points for discriminating two groups was the GADAb level of 13.6 U/ml, age of diabetes onset of 47 years, duration before diagnosis of 5 years, and fasting C-peptide of 0.65 ng/ml.Clinical, biochemical and genetic characteristics of patients with NIR-SPIDDM are different from those of IR-SPIDDM patients. Age of diabetes onset, duration before

  16. Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

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    Alba Grifoni

    2017-10-01

    Full Text Available BackgroundDengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV. To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua.MethodsHLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays.ResultsWe detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005. This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80

  17. Standardized observation of neighbourhood disorder: does it work in Canada?

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    Zaidi Qamar

    2010-02-01

    Full Text Available Abstract Background There is a growing body of evidence that where you live is important to your health. Despite numerous previous studies investigating the relationship between neighbourhood deprivation (and structure and residents' health, the precise nature of this relationship remains unclear. Relatively few investigations have relied on direct observation of neighbourhoods, while those that have were developed primarily in US settings. Evaluation of the transferability of such tools to other contexts is an important first step before applying such instruments to the investigation of health and well-being. This study evaluated the performance of a systematic social observational (SSO tool (adapted from previous studies of American and British neighbourhoods in a Canadian urban context. Methods This was a mixed-methods study. Quantitative SSO ratings and qualitative descriptions of 176 block faces were obtained in six Toronto neighbourhoods (4 low-income, and 2 middle/high-income by trained raters. Exploratory factor analysis was conducted with the quantitative SSO ratings. Content analysis consisted of independent coding of qualitative data by three members of the research team to yield common themes and categories. Results Factor analysis identified three factors (physical decay/disorder, social accessibility, recreational opportunities, but only 'physical decay/disorder' reflected previous findings in the literature. Qualitative results (based on raters' fieldwork experiences revealed the tool's shortcomings in capturing important features of the neighbourhoods under study, and informed interpretation of the quantitative findings. Conclusions This study tested the performance of an SSO tool in a Canadian context, which is an important initial step before applying it to the study of health and disease. The tool demonstrated important shortcomings when applied to six diverse Toronto neighbourhoods. The study's analyses challenge previously

  18. Sorbitan sesquioleate

    DEFF Research Database (Denmark)

    Bennike, Niels Højsager; Johansen, Jeanne Duus

    2016-01-01

    BACKGROUND: Sorbitan sesquioleate (SSO) has been added to fragrance mix I (FM I) as an emulsifier since the 1990s. Being a contact allergen itself, SSO has the potential to cause false-positive reactions to FM I. Recent results obtained with selected FM I-positive patients have shown that 5% have...... concomitant positive reactions to SSO. OBJECTIVES: To investigate the 5-year prevalence of contact allergy to SSO and evaluate the importance of SSO allergy when patch test results for FM I are interpreted. METHODS: This was a retrospective database study of consecutively patch tested eczema patients (n = 4......,637) from 2010 to 2014. All patients were tested with our baseline series including FM I and SSO 20% in pet. RESULTS: Sensitization to SSO was identified in 9 (0.2%) patients. The proportion of FM I-positive patients with concomitant positive reactions to SSO was 1.4%. CONCLUSIONS: SSO is a rare cause...

  19. DNA polymorphism of HLA class II genes in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Cowland, J B; Andersen, V; Halberg, P

    1994-01-01

    We investigated the DNA restriction fragment length polymorphism (RFLP) of the major histocompatibility complex (MHC) genes: HLA-DRB, -DQA, -DQB, -DPB in 24 Danish patients with systemic lupus erythematosus (SLE) and in 102 healthy Danes. A highly significant increase of the frequency of the DR3......- and DRw6-associated 7.00 kb DRB TaqI DNA fragment was found in SLE patients compared to normal controls (83.3% vs 35.5%; RR = 9.1, p 1*0501-associated 4.56 kb DQA TaqI fragment and the DRB3*01/03-associated 9.79 kb TaqI fragment were also found to be significantly...... increased in SLE patients (70.8% vs 29.7%; RR = 5.8, p 1%; RR = 4.3, p

  20. The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population.

    Science.gov (United States)

    Werneck, Lineu Cesar; Lorenzoni, Paulo José; Arndt, Raquel Cristina; Kay, Cláudia Suemi Kamoi; Scola, Rosana Herminia

    2016-08-01

    To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil. We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques. We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS. Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.

  1. Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G--possible implications for human reproduction and autoimmune disease

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Christiansen, Ole B

    2005-01-01

    ). We found a significant linkage disequilibrium between HLA-DR3 and HLA-G*010102 in both the RSA and control populations. For all four studied HLA loci, the alleles in the haplotype HLA-DRB1*03.DQA1*05.DQB1*02.G*010102 was in clear linkage disequilibrium. This HLA haplotype has repeatedly been...... associated with different autoimmune diseases but also with RSA. The G*010102 allele includes a 14-bp sequence polymorphism in the 3' untranslated region of the gene, which has been associated with differences in HLA-G mRNA alternative splicing and stability. This 14-bp polymorphism has also been associated...... with RSA, pre-eclampsia, and outcome of in vitro fertilization. Implications of HLA polymorphism--and other polymorphic genes in the MHC for pregnancy outcome--and for autoimmune diseases during pregnancy are discussed....

  2. Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Hansen, Kasper Lage

    2009-01-01

    genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC......To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1...... region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein...

  3. Associação entre HLA e leucemia em uma população brasileira de etnia mista Association between HLA and leukemia in a mixed Brazilian population

    Directory of Open Access Journals (Sweden)

    Lúcia Aparecida Barion

    2007-06-01

    Full Text Available OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda, 50 com LMA (leucemia mielóide aguda e 78 com LMC (leucemia mielóide crônica. MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers, ambas da One Lambda (Canoga Park, CA, US. RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95%IC = 0,94-10,44; P = 0,03; OR = 3,61; 95%IC = 0,47-27,64, respectivamente, quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95%IC = 1,25-4,67 foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95%IC = 1,46-7,40 e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95%IC = 1,36-3,46 e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95%IC = 1,34-4,16 foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia, 50 with AML (acute myeloid leukemia and 78 with CML (chronic myeloid leukemia. METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers (One Lambda, Canoga Park, CA, USA. RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively, than in controls. In patients with AML, the

  4. The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.

    2010-01-01

    Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein......-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

  5. Rheumatoid arthritis and Swine influenza vaccine: a case report.

    Science.gov (United States)

    Basra, Gurjot; Jajoria, Praveen; Gonzalez, Emilio

    2012-01-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Multiple scientific articles have documented that vaccinations for influenza, MMR, and HBV, to name a few, could be triggers of RA in genetically predisposed individuals. However, there is limited data regarding the association of swine flu vaccine (H1N1) and RA. We report the case of a Mexican American female who developed RA right after vaccination with H1N1 vaccine. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR β chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in Mexican Americans. Hence, certain individuals with the presence of the "shared epitope" may develop RA following specific vaccinations. To our knowledge, this is the first reported case of RA following vaccination with the swine flu vaccine.

  6. The role of KIR2DS1 in multiple sclerosis--KIR in Portuguese MS patients.

    Science.gov (United States)

    Bettencourt, Andreia; Silva, Ana Martins; Carvalho, Cláudia; Leal, Bárbara; Santos, Ernestina; Costa, Paulo P; Silva, Berta M

    2014-04-15

    Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. We observed a negative association between the activating KIR2DS1 gene and MS (adjusted OR=0.450, p=0.030) independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

    Directory of Open Access Journals (Sweden)

    Sun Hee Lee

    2013-03-01

    Full Text Available Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea.

  8. Adaptability of the Saccharomyces cerevisiae yeasts to wine fermentation conditions relies on their strong ability to consume nitrogen

    Science.gov (United States)

    2018-01-01

    Saccharomyces cerevisiae strains are genetically diverse, largely as a result of human efforts to develop strains specifically adapted to various fermentation processes. These adaptive pressures from various ecological niches have generated behavioral differences among these strains, particularly in terms of their nitrogen consumption capacities. In this work, we characterize this phenotype by the specific quantity of nitrogen consumed under oenological fermentation conditions using a new approach. Indeed, unlike previous studies, our experiments were conducted in an environment containing excess nitrogen, eliminating the nitrogen limitation/starvation factor that is generally observed in fermentation processes. Using these conditions, we evaluated differences in the nitrogen consumption capacities for a set of five strains from diverse origins. The strains presented extremely different phenotypes and variations in their capacities to take up nitrogen from a wine fermentation environment. These variations reflect the differences in the nitrogen uptake capacities between wine and non-wine strains. Finally, the strains differed in their ability to adapt to the nitrogen composition of the environment, leading to variations in the cellular stress states, fermentation performances and the activity of the nitrogen sensing signaling pathway. PMID:29432462

  9. Developmental shaping of dendritic arbors in Drosophila relies on tightly regulated intra-neuronal activity of protein kinase A (PKA).

    Science.gov (United States)

    Copf, Tijana

    2014-09-15

    Dendrites develop morphologies characterized by multiple levels of complexity that involve neuron type specific dendritic length and particular spatial distribution. How this is developmentally regulated and in particular which signaling molecules are crucial in the process is still not understood. Using Drosophila class IV dendritic arborization (da) neurons we test in vivo the effects of cell-autonomous dose-dependent changes in the activity levels of the cAMP-dependent Protein Kinase A (PKA) on the formation of complex dendritic arbors. We find that genetic manipulations of the PKA activity levels affect profoundly the arbor complexity with strongest impact on distal branches. Both decreasing and increasing PKA activity result in a reduced complexity of the arbors, as reflected in decreased dendritic length and number of branching points, suggesting an inverted U-shape response to PKA. The phenotypes are accompanied by changes in organelle distribution: Golgi outposts and early endosomes in distal dendritic branches are reduced in PKA mutants. By using Rab5 dominant negative we find that PKA interacts genetically with the early endosomal pathway. We test if the possible relationship between PKA and organelles may be the result of phosphorylation of the microtubule motor dynein components or Rab5. We find that Drosophila cytoplasmic dynein components are direct PKA phosphorylation targets in vitro, but not in vivo, thus pointing to a different putative in vivo target. Our data argue that tightly controlled dose-dependent intra-neuronal PKA activity levels are critical in determining the dendritic arbor complexity, one of the possible ways being through the regulation of organelle distribution. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Self-control depletion in tufted capuchin monkeys (Sapajus spp.): does delay of gratification rely on a limited resource?

    Science.gov (United States)

    Petrillo, Francesca De; Micucci, Antonia; Gori, Emanuele; Truppa, Valentina; Ariely, Dan; Addessi, Elsa

    2015-01-01

    Self-control failure has enormous personal and societal consequences. One of the most debated models explaining why self-control breaks down is the Strength Model, according to which self-control depends on a limited resource. Either previous acts of self-control or taking part in highly demanding cognitive tasks have been shown to reduce self-control, possibly due to a reduction in blood glucose levels. However, several studies yielded negative findings, and recent meta-analyses questioned the robustness of the depletion effect in humans. We investigated, for the first time, whether the Strength Model applies to a non-human primate species, the tufted capuchin monkey. We tested five capuchins in a self-control task (the Accumulation task) in which food items were accumulated within individual's reach for as long as the subject refrained from taking them. We evaluated whether capuchins' performance decreases: (i) when tested before receiving their daily meal rather than after consuming it (Energy Depletion Experiment), and (ii) after being tested in two tasks with different levels of cognitive complexity (Cognitive Depletion Experiment). We also tested, in both experiments, how implementing self-control in each trial of the Accumulation task affected this capacity within each session and/or across consecutive sessions. Repeated acts of self-control in each trial of the Accumulation task progressively reduced this capacity within each session, as predicted by the Strength Model. However, neither experiencing a reduction in energy level nor taking part in a highly demanding cognitive task decreased performance in the subsequent Accumulation task. Thus, whereas capuchins seem to be vulnerable to within-session depletion effects, to other extents our findings are in line with the growing body of studies that failed to find a depletion effect in humans. Methodological issues potentially affecting the lack of depletion effects in capuchins are discussed.

  11. Catalytic ozonation of oxalate with a cerium supported palladium oxide: An efficient degradation not relying on hydroxyl radical oxidation

    KAUST Repository

    Zhang, Tao; Li, Weiwei; Croue, Jean-Philippe

    2011-01-01

    The cerium supported palladium oxide (PdO/CeO 2) at a low palladium loading was found very effective in catalytic ozonation of oxalate, a probe compound that is difficult to be efficiently degraded in water with hydroxyl radical oxidation and one of the major byproducts in ozonation of organic matter. The oxalate was degraded into CO 2 during the catalytic ozonation. The molar ratio of oxalate degraded to ozone consumption increased with increasing catalyst dose and decreasing ozone dosage and pH under the conditions of this study. The maximum molar ratio reached around 1, meaning that the catalyst was highly active and selective for oxalate degradation in water. The catalytic ozonation, which showed relatively stable activity, does not promote hydroxyl radical generation from ozone. Analysis with ATR-FTIR and in situ Raman spectroscopy revealed that 1) oxalate was adsorbed on CeO 2 of the catalyst forming surface complexes, and 2) O 3 was adsorbed on PdO of the catalyst and further decomposed to surface atomic oxygen (*O), surface peroxide (*O 2), and O 2 gas in sequence. The results indicate that the high activity of the catalyst is related to the synergetic function of PdO and CeO 2 in that the surface atomic oxygen readily reacts with the surface cerium-oxalate complex. This kind of catalytic ozonation would be potentially effective for the degradation of polar refractory organic pollutants and hydrophilic natural organic matter. © 2011 American Chemical Society.

  12. Relying on Visiting Foreign Doctors for Fistula Repair: The Profile of Women Attending Fistula Repair Surgery in Somalia.

    Science.gov (United States)

    Gele, Abdi A; Salad, Abdulwahab M; Jimale, Liban H; Kour, Prabhjot; Austveg, Berit; Kumar, Bernadette

    2017-01-01

    Obstetric fistula is treatable by surgery, although access is usually limited, particularly in the context of conflict. This study examines the profile of women attending fistula repair surgery in three hospitals in Somalia. A cross-sectional study was conducted in Somalia from August to September 2016. Structured questionnaires were administered to 81 women who registered for fistula repair surgery in the Garowe, Daynile, and Kismayo General Hospitals in Somalia. Findings revealed that 70.4% of the study participants reported obstetric labor as the cause of their fistula, and 29.6% reported iatrogenic causes. Regarding the waiting time for the repair surgery, 45% waited for the surgery for over one year, while the rest received the surgery within a year. The study suggests that training for fistula surgery has to be provided for healthcare professionals in Somalia, fistula centers should be established, and access to these facilities has to be guaranteed for all patients who need these services.

  13. Marquardt's Phi mask: pitfalls of relying on fashion models and the golden ratio to describe a beautiful face.

    Science.gov (United States)

    Holland, E

    2008-03-01

    Stephen Marquardt has derived a mask from the golden ratio that he claims represents the "ideal" facial archetype. Many have found his mask convincing, including cosmetic surgeons. However, Marquardt's mask is associated with numerous problems. The method used to examine goodness of fit with the proportions in the mask is faulty. The mask is ill-suited for non-European populations, especially sub-Saharan Africans and East Asians. The mask also appears to approximate the face shape of masculinized European women. Given that the general public strongly and overwhelmingly prefers above average facial femininity in women, white women seeking aesthetic facial surgery would be ill-advised to aim toward a better fit with Marquardt's mask. This article aims to show the proper way of assessing goodness of fit with Marquardt's mask, to address the shape of the mask as it pertains to masculinity-femininity, and to discuss the broader issue of an objective assessment of facial attractiveness. Generalized Procrustes analysis is used to show how goodness of fit with Marquardt's mask can be assessed. Thin-plate spline analysis is used to illustrate visually how sample faces, including northwestern European averages, differ from Marquardt's mask. Marquardt's mask best describes the facial proportions of masculinized white women as seen in fashion models. Marquardt's mask does not appear to describe "ideal" face shape even for white women because its proportions are inconsistent with the optimal preferences of most people, especially with regard to femininity.

  14. Evaluation Techniques of Creating Coherence in Poems of Kaiser Aminpour Relying on the Theory of Halliday’s Linguistics

    Directory of Open Access Journals (Sweden)

    Reza Sattari

    2016-05-01

    Full Text Available AbstractOne of the linguistics theories that are utilized in present age in the analysis of literary texts is the theory of Halliday’s linguistics which is called theory of systemic - functional linguistics. Halliday’s theory in the second half of the twentieth century, in contrast to the "generative linguistics" approach, which is based on formal language like a mental and individual phenomenon.    Hallidayan called the semantic, literal, syntax and logical relationship of words as coherence of a text and believes that the coherence of the text, includes all the semantic relations by which, every piece of speech or writing can serve as text. Hence, cohesion, referred to relations that relates all elements of a sentence to the elements of other sentences. From Hallidayan's  point of view, elements of coherence of a text are divided into two parts: grammatical and lexical. Grammatical cohesion includes factors such as referrals, replacements, removals and relevancy, and lexical coherence includes repetition and collocation in literary language.   Kaiser is one of the contemporary famous poets that have composed many poets in different molds of poetry. Kaiser Manipur's poems benefit the integration due to the poet's fluency in Persian and his familiarity with the vocabulary and grammatical and lexical capacities of Persian literature. In this research, we have studied the cohesion in Kaiser Manipur's poems from two views of lexical and grammatical by using Holidaying theory of coherence as well as the techniques that the poet has applied to reach the cohesion in his poems.    The method of research in the present paper is descriptive-analytical and all the information and data has been collected from the sources of library and electronic. In this paper, we first briefly discussed the Holidaying coherence theory, and then, with a special approach to this theory, the most important techniques that Kaiser Manipur has benefited to create the coherence in his poems and poetry, analyzed and investigated.   The Research results indicate that the poems of Kaiser Manipur have a specific integration due to the poet's fluency in Persian and his familiarity with the vocabulary and grammatical and lexical capacities of Persian literature. Hence, techniques of creating coherence in two aspects of grammatical cohesion and lexical cohesion in Kaiser Manipur's poetry are considerable. Grammatical coherence in his poems is achieved through techniques such as references, omission, and relevance. And the techniques of lexica coherence in his poems are: using phonemes, repeating the words, pun, repeated sentence, the balance, the heart of the matter, proportion, contrast, sequence and so on.    Kaiser Aminpour has widely used the techniques of lexical and grammatical coherence in his poems, so that in most of his poems we can see several techniques used together in a way to reach the mentioned coherence. Hence, we can say he is a poet who knows his language as well as words and has the complete power of selection and combination of words and sentences. And his poems are very coherent and the sentences and phrases are intertwined and related to each other in his poetry.Keywords: Kaiser Aminpour, Hallidayan, functional linguistics, grammatical cohesion, lexical cohesion.References 1.      Abdollahi, Manije (2005. Vertical link and semantic cohesion in the ghazals of Hafez. Journal of Humanities and Social Sciences, University of Shiraz, (Vol. 22. No 3(44. P.p: 124- 134. [In Persian].2.      Afrashi, Azita (1999. A look to the issue of collocation of words. Language and Literature, No 7 & 8. p.p: 73- 83. [In Persian].3.      Aghahosseini, H. & Gholami, Mojahed. (2010. Indian poetry style aesthetic effects on the resistance poetry of Kaiser Aminpour's poetry. Journal of resistance literature at Kerman Shahid Bahonar University. Year, 1. No, 2. P.p: 1- 29. [In Persian]. 4.      Ahmadzadeh, Mostafa. (2008. Linguistic interpretation of Surah Al-Asr. Islamic Studies: Quran and Hadith Sciences. Year 40. No, 3/18. P.p: 11-35. [In Persian].5.       Alavi-moghaddam, M. (1998. Contemporary literary criticism theories (formalism and structuralism. Tehran: Samt. [In Persian].6.      Aminpour, Kaisar (2011. Complete collection of kaisar Aminpour's poems. 8th ed., Tehran: Morvarid. [In Persian].Abdollahi, M. (2005.  7.      Behjo, Zohre (1998. Encoding scheme of methods of coherence in Persian language. Farhang, No 25 & 26. P.p: 189- 212. [In Persian].8.      Fotohi, M. (2008. Three voices, three colors, three styles of Aminpour’s poem. Literature Studies, University of Guilan. No 5. P.p: 9-30. [In Persian].9.      Ghobadi, H. & Rezaei-Jamkarani, A. (2011. Review, analysis and criticism of four Persian odes based on the teachings of systemic-functional linguistics. Journal of Persian Language and Literature. No 20. P.p: 69- 93. [In Persian].10.  Gholamhosseinzade, GH. & Norouzi, H. (2010.  Role of Phonetic repeating in lexical Cohesion in prosodic Persian poetry. Journal of Literature and Language University of Kerman. No, 27. P.p: 251- 281. [In Persian].11.  Halliday, M. A. K & Hasan, R. (1976 Cohesion in English. London: Longman, [In English].12.  Halliday, M. A. K. (1985. An Introduction to Functional Grammar. London: Edward Arnold. [In English].13.  Jahangiri, N. & Zakipour, Sh. (2005. Lexical cohesion in Persian short stories for children. Literary Notes (Journal of Ferdowsi University of Mashhad. No 151. P.p: 1-20. [In Persian].14.  Khanjan, A. & Mirza, Z. (2006. Introduction to the functional poetry (linguistic approaches. Journal of Persian Language and Literature. No 7. P.p: 83- 101. [In Persian].15.  Lotfipour-saedi, K. (1992. An introduction to the principles and methods of translation. Tehran: Academic publishing. [In Persian].16.  Martine, A. (2001. Phonetic transformation balance. (H. Milanian Trans. Terhan: Hermes. [In Persian].17.  Moein od-Dini, F. (2003.  Techniques to create coherence in kalila and demna. Farhang, No 47 & 47. P.p: 303- 326. [In Persian].18.  Mohajer, M. & Nabavi, M. (1997. Towards the linguistic poetry: the functional approach. Tehran: Markaz. [In Persian].19.  Natel Khanlari, P. (2007. Persian poetry weight. 7th ed., Tehran: toos. [In Persian].20.  Panahi, S. (2002. The process of collocation and collocation compounds in Persian language. Journal of Academy. No19. P.p: 199- 211. [In Persian].21.  Rastgoo, M. (2004. Speak art layout (art of badie. Tehran: Samt. [In Persian].22.  Rouhani, M. (2011.  Study of Repeats' Functions in Contemporary Poetry (based on poetry of Sepehri, Shamloo and Forough. Journal of Boostan Adab (university of Shiraz. Year 3. No 2/8. P.p: 145- 168. [In Persian].23.  Safavi, K. (2008. Introduction to Semantics. 3rd ed., Tehran: Sore-ye Mehr. [In Persian]. 24.  Safavi, K. (1994. From linguistics to literature. (Vol: 1. Tehran: Cheshme. [In Persian].25.  Salehi, F. (2007.  Semantics and functional grammar of Halliday. Literature Book of the Month. No 8. P.p: 32-41. [In Persian].26.  Sarli, N. & Ishani, T. (2011.  Coherence and Coordination of cohesion Theory and its Application in a Minimal Story Persian (The Story of the Ladder. Journal of Language Scholarships (university of az-Zahra. Year 2. No 4. P.p: 51- 77. [In Persian].27.  Shabanloo, A. & Maleksabet, M. & Jalali, Y. (2008.  Grammatical cohesion process in the long poem of am'aq Bukhari. Journal of Gawhar-i Guya. No 5. P.p: 165- 188. [In Persian].28.  Shafi’ee kadkani, M. (2005. Music of Lyrics. (8th ed., Tehran: Agah. [In Persian].29.  Shamisa, S. (2007. Figures of speech: a new look to Ba'die. 2nd ed., Tehran: Mitra. [In Persian].30.  Vafaei, A. & Alinoori, Z. (2010. Artistic symmetry in two axes of succession and Companion in poems of Kaiser Aminpour. Journal of Persian Language and Literature. Year 2. No 6. P: 99- 118. [In Persian].31.  Velek, R. & Varen, A. (2003. Theory of Literatur. (Z. Movahhed & P. Mohajer Trans. Tehran: Elmi- Farhangi. [In Persian].Yahaghi, M. & Fallahi, M. (2010.  Saadi's and Bidel Dehlavi's sonnets text cohesion, evaluation and comparison of ten sonnets of Sa'di, and ten sonnets of Bidel. Journal of Literature and Language University of Kerman. No 27. P: 327- 346. [In Persian].

  15. Organizational Strategic Planning and Execution: Should Governmental Organizations Rely on Strategic Planning for the Success of the Organization?

    National Research Council Canada - National Science Library

    Young, Lester; Reynolds, Thomas E; Harris, II, Thomas L

    2007-01-01

    .... The utilization of this tool can yield positive results for many companies and organizations. On the other hand, if the strategic plan is not utilized, it becomes a costly paperweight on a table in the executive suite...

  16. Do countries rely on the World Health Organization for translating research findings into clinical guidelines? A case study.

    Science.gov (United States)

    Noor, Ramadhani A; Geldsetzer, Pascal; Bärnighausen, Till; Fawzi, Wafaie

    2016-10-06

    The World Health Organization's (WHO) antiretroviral therapy (ART) guidelines have generally been adopted rapidly and with high fidelity by countries in sub-Saharan Africa. Thus far, however, WHO has not published specific guidance on nutritional care and support for (non-pregnant) adults living with HIV despite a solid evidence base for some interventions. This offers an opportunity for a case study on whether national clinical guidelines in sub-Saharan Africa provide concrete recommendations in the face of limited guidance by WHO. This study, therefore, aims to determine if national HIV treatment guidelines in sub-Saharan Africa contain specific guidance on nutritional care and support for non-pregnant adults living with HIV. We identified the most recent national HIV treatment guidelines in sub-Saharan African countries with English as an official language. Using pre-specified criteria, we determined for each guideline whether it provides guidance to clinicians on each of five components of nutritional care and support for adults living with HIV: assessment of nutritional status, dietary counseling, micronutrient supplementation, ready-to-use therapeutic or supplementary foods, and food subsidies. We found that national HIV treatment guidelines in sub-Saharan Africa generally do not contain concrete recommendations on nutritional care and support for non-pregnant adults living with HIV. Given that decisions on nutritional care and support are inevitably being made at the clinician-patient level, and that clinicians have a relative disadvantage in systematically identifying, summarizing, and weighing up research evidence compared to WHO and national governments, there is a need for more specific clinical guidance. In our view, such guidance should at a minimum recommend daily micronutrient supplements for adults living with HIV who are in pre-ART stages, regular dietary counseling, periodic assessment of anthropometric status, and additional nutritional management of undernourished patients. More broadly, our findings suggest that countries in sub-Saharan Africa look to WHO for guidance in translating evidence into clinical guidelines. It is, thus, likely that the development of concrete recommendations by WHO on nutritional interventions for people living with HIV would lead to more specific guidelines at the country-level and, ultimately, better clinical decisions and treatment outcomes.

  17. Can we rely on Swedish granites and gneisses as sage host rock for hazardous waste disposal during future geological periods?

    International Nuclear Information System (INIS)

    Morfeldt, C.O.; Morfeldt, D.

    1991-01-01

    The rapid growth of our industrial societies, together with an increased awareness and sense of responsibility towards the environment in most countries, has made us being to understand the urgency of halting and preventing further pollution and destruction of irreparable environments. The main issue sat present focus on neutralizing the harmful effects of toxic waste by isolating it from the biosphere for long periods of time, perhaps for many hundreds of thousands of years. These issues no longer focus on radioactive substances and their harmful ionizing radiation effects but also on heavy alloys and chemical pollutants generated during transformation processes of different types of waste, or through incineration of waste. Ash and sedimentary deposits from sewage plants for example, also contain heavy alloys. (au)

  18. Do we really rely on fast for decision-making in the management of blunt abdominal trauma?

    Science.gov (United States)

    Carter, Jeffrey W; Falco, Mark H; Chopko, Michael S; Flynn, William J; Wiles Iii, Charles E; Guo, Weidun Alan

    2015-05-01

    The Focused Assessment with Sonography in Trauma examination (FAST) is currently taught and recommended in the ATLS(®), often as an addendum to the primary survey for patients with blunt abdominal trauma. Although it is non-invasive and rapidly performed at bedside, the utility of FAST in blunt abdominal trauma has been questioned. We designed this study to examine our hypothesis that FAST is not an efficacious screening tool for identifying intra-abdominal injuries. We performed a retrospective chart review of all patients with confirmatory diagnosis of blunt abdominal injuries with CT and/or laparotomy for a period of 1.5 years (from 7/2009 to 11/2010). FAST was performed by ED residents and considered positive when free intra-abdominal fluid was visualized. Abdominal CT, or exploratory laparotomy findings were used as confirmation of intra-abdominal injury. A total of 1671 blunt trauma patients were admitted to and evaluated in the Emergency Department during a 1½ year period and 146 patients were confirmed intra-abdominal injuries by CT and/or laparotomy. Intraoperative findings include injuries to the liver, spleen, kidneys, and bowels. In 114 hemodynamically stable patients, FAST was positive in 25 patients, with a sensitivity of 22%. In 32 hemodynamically unstable patients, FAST was positive in 9 patients, with a sensitivity of 28%. A free peritoneal fluid and splenic injury are associated with a positive FAST on univariate analysis, and are the independent predictors for a positive FAST on multiple logistic regression. FAST has a very low sensitivity in detecting blunt intraabdominal injury. In hemodynamically stable patients, a negative FAST without a CT may result in missed intra-abdominal injuries. In hemodynamically unstable blunt trauma patients, with clear physical findings on examination, the decision for exploratory laparotomy should not be distracted by a negative FAST. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The Importance of Relying on the Manual: Scoring Error Variance in the WISC-IV Vocabulary Subtest

    Science.gov (United States)

    Erdodi, Laszlo A.; Richard, David C. S.; Hopwood, Christopher

    2009-01-01

    Classical test theory assumes that ability level has no effect on measurement error. Newer test theories, however, argue that the precision of a measurement instrument changes as a function of the examinee's true score. Research has shown that administration errors are common in the Wechsler scales and that subtests requiring subjective scoring…

  20. How much will BC rely on incoming LNG and locally produced natural gas to fuel future generation capacity

    International Nuclear Information System (INIS)

    Boychuk, L.A.

    2005-01-01

    The British Columbia Utilities Commission (BCUC) works with public utilities to determine where resource additions are needed in order to ensure safe, reliable and convenient service to utility customers. All public utilities in the province are required to file resource plans in order to enhance the effectiveness of the BCUC and to protect ratepayers from poor utility expenditure decisions. The BCUC also ensures that utilities have adequate supply to meet demand. This paper outlined energy policy actions plans for the province of British Columbia. The BCUC will regulate BC hydro rates and will review the Vancouver Island Generation Project (VIGP) to determine if it is the most cost-effective means to reliably meet power needs on the island. Electricity distributors will acquire new supply on a least-cost basis, with regulatory oversight by BCUC. The role of the private sector in developing new electricity generation was also discussed, along with alternative energy development opportunities, such as the potential liquefied natural gas (LNG) import project by Galveston at Kitimat and WestPac Terminals' project at Prince Rupert

  1. Do Adults with Cochlear Implants Rely on Different Acoustic Cues for Phoneme Perception than Adults with Normal Hearing?

    Science.gov (United States)

    Moberly, Aaron C.; Lowenstein, Joanna H.; Tarr, Eric; Caldwell-Tarr, Amanda; Welling, D. Bradley; Shahin, Antoine J.; Nittrouer, Susan

    2014-01-01

    Purpose: Several acoustic cues specify any single phonemic contrast. Nonetheless, adult, native speakers of a language share weighting strategies, showing preferential attention to some properties over others. Cochlear implant (CI) signal processing disrupts the salience of some cues: In general, amplitude structure remains readily available, but…

  2. Individuals with high obsessive-compulsive tendencies or undermined confidence rely more on external proxies to access their internal states.

    Science.gov (United States)

    Zhang, Zhongming; Wang, Mengyun; Miao, Xiaocui; Li, Yijuan; Hitchman, Glenn; Yuan, Zhen

    2017-03-01

    The Seeking Proxies for Internal States (SPIS) hypothesis predicts that obsessive-compulsive disorder (OCD) is associated with a deficit in subjective convictions, which may lead to a reliance on external substitutes for the perceptions of an individual's internal states. Two well-designed studies were performed for the present work that adopted a false bio-feedback procedure in a muscle tension task to examine the SPIS hypothesis. The false bio-feedback paradigm was used to investigate our hypothesis. NeXus-10 Mark II hardware and V2011 BioTrace + software (Mind Media B.V., Herten, Netherlands) were utilized to measure the muscle tension of the flexor carpiulnaris muscle, which characterized the target's internal state. In addition, false EMG changes were recorded and displayed on a computer monitor and were considered external proxies. Study 1 demonstrated that the participants with high obsessive-compulsive (OC) tendencies were more affected by the false bio-feedback and exhibited lower confidence in their judgments regarding their muscle tension compared with the participants with low OC tendencies. These findings indicate that subjects with high OC tendencies were more influenced by self-perception effects. In contrast, the subjects in the undermined confidence group in Study 2 were more easily influenced by the false bio-feedback compared with the control group, which suggests that the subjects in the undermined confidence group were more affected by self-perception effects. We did not combine the undermined confidence with OC tendencies or OCD symptoms in our paradigm to investigate their joint effects on self-perception. Our findings provide further evidence that supports the SPIS hypothesis, which indicates that OC tendencies and the confidence in an individual's recognition of internal states appear to have similar effects on the assessment of internal states and reliance on proxies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Marketing communications in industrial B2b markets enhancing the value of the corporate brand relying on common added values

    Directory of Open Access Journals (Sweden)

    Jose Ignacio Monrabal

    2013-09-01

    Full Text Available Today, industrial Business-to-Business (B2B markets are mainly characterized by a highly trained customer for making rational decisions in a highly competitive and global market, requiring more than ever organizations to approach their markets with a single and consistent message. Such demanding scenario requires to define a corporate brand transmitting in one message all the advantages that a Customer may appreciate in the long-term, based not only on what the company stands for in the market, but also the benefits of all its products throughout its portfolio. Such elements are referred as Common Added Values (CAVs, being some general examples the technology, quality, innovation and reliability; the capacity, infrastructure and distribution network; after-sales service policies, support and training; or the price and financial policies. This paper tries to explain the source of this need, describing the main differences between a brand communications model focused on the product or including the main B2B corporate values; and highlighting the main CAVs, to get an industry player either small or large, can succeed in generating brand equity through an integrated marketing communications strategy.

  4. Organizational Strategic Planning and Execution: Should Governmental Organizations Rely on Strategic Planning for the Success of the Organization?

    Science.gov (United States)

    2007-06-01

    Competition that it faces. 16 The analysis of internal factors will include (IV) the company’s marketing mix ; (V) the internal resources; and (VI) a variety...Government; Economy; Socio-Demography; Technology) III Industry & Competition IV Marketing Mix (Outputs) A B C V Internal Resource

  5. Can We Rely on Predicted Basal Metabolic Rate in Patients With Intestinal Failure on Home Parenteral Nutrition?

    Science.gov (United States)

    Skallerup, Anders; Nygaard, Louis; Olesen, Søren Schou; Vinter-Jensen, Lars; Køhler, Marianne; Rasmussen, Henrik Højgaard

    2017-09-01

    Intestinal failure (IF) is a serious and common complication of short bowel syndrome with patients depending on parenteral nutrition (PN) support. Effective nutrition management requires an accurate estimation of the patient's basal metabolic rate (BMR) to avoid underfeeding or overfeeding. However, indirect calorimetry, considered the gold standard for BMR assessment, is a time- and resource-consuming procedure. Consequently, several equations for prediction of BMR have been developed in different settings, but their accuracy in patients with IF are yet to be investigated. We evaluated the accuracy of predicted BMR in clinically stable patients with IF dependent on home parenteral nutrition (HPN). In total, 103 patients with IF were included. We used indirect calorimetry for assessment of BMR and calculated predicted BMR using different equations based on anthropometric and/or bioelectrical impedance parameters. The accuracy of predicted BMR was evaluated using Bland-Altman analysis with measured BMR as the gold standard. The average measured BMR was 1272 ± 245 kcal/d. The most accurate estimations of BMR were obtained using the Harris-Benedict equation (mean bias, 14 kcal/d [ P = .28]; limits of agreement [LoA], -238 to 266 kcal/d) and the Johnstone equation (mean bias, -16 kcal/d [ P = .24]; LoA, -285 to 253 kcal/d). For both equations, 67% of patients had a predicted BMR from 90%-110% All other equations demonstrated a statistically and clinically significant difference between measured and predicted BMR. The Harris-Benedict and Johnstone equations reliably predict BMR in two-thirds of clinically stable patients with IF on HPN.

  6. Diagnosis of sclerosing hemangioma of lung: Don′t rely on fine-needle aspiration cytology diagnosis alone

    Directory of Open Access Journals (Sweden)

    Kaushik Saha

    2013-01-01

    Full Text Available Sclerosing hemangioma is a rare variety of benign pulmonary neoplasm. It usually presents as asymptomatic, solitary, peripheral, circumscribed lesions in middle-aged women. Here, we describe a 46-year-old woman presenting to us for evaluation of right parahilar lung mass. Previous chest radiography done 10 years back showed a lung mass of almost similar size. Computed Tomography (CT-guided fine-needle aspiration cytology (FNAC was suggestive of adenocarcinoma of lung. A well-circumscribed, capsulated, ovoid mass measuring 5.6 cm × 4 cm × 3 cm, adjacent to the transverse fissure of the right lung was excised by lateral thoracotomy. Histopathological examination along with immunohistochemistry was suggestive of sclerosing hemangioma of lung. A pathologist must consider the clinicoradiological features before coming to a final diagnosis of lung malignancy from FNAC. Whenever there is any confusion regarding lung mass, thoracotomy must be done for arriving at an exact diagnosis from histopathology.

  7. Multiple source genes of HAmo SINE actively expanded and ongoing retroposition in cyprinid genomes relying on its partner LINE

    Directory of Open Access Journals (Sweden)

    Gan Xiaoni

    2010-04-01

    Full Text Available Abstract Background We recently characterized HAmo SINE and its partner LINE in silver carp and bighead carp based on hybridization capture of repetitive elements from digested genomic DNA in solution using a bead-probe 1. To reveal the distribution and evolutionary history of SINEs and LINEs in cyprinid genomes, we performed a multi-species search for HAmo SINE and its partner LINE using the bead-probe capture and internal-primer-SINE polymerase chain reaction (PCR techniques. Results Sixty-seven full-size and 125 internal-SINE sequences (as well as 34 full-size and 9 internal sequences previously reported in bighead carp and silver carp from 17 species of the family Cyprinidae were aligned as well as 14 new isolated HAmoL2 sequences. Four subfamilies (type I, II, III and IV, which were divided based on diagnostic nucleotides in the tRNA-unrelated region, expanded preferentially within a certain lineage or within the whole family of Cyprinidae as multiple active source genes. The copy numbers of HAmo SINEs were estimated to vary from 104 to 106 in cyprinid genomes by quantitative RT-PCR. Over one hundred type IV members were identified and characterized in the primitive cyprinid Danio rerio genome but only tens of sequences were found to be similar with type I, II and III since the type IV was the oldest subfamily and its members dispersed in almost all investigated cyprinid fishes. For determining the taxonomic distribution of HAmo SINE, inter-primer SINE PCR was conducted in other non-cyprinid fishes, the results shows that HAmo SINE- related sequences may disperse in other families of order Cypriniforms but absent in other orders of bony fishes: Siluriformes, Polypteriformes, Lepidosteiformes, Acipenseriformes and Osteoglossiforms. Conclusions Depending on HAmo LINE2, multiple source genes (subfamilies of HAmo SINE actively expanded and underwent retroposition in a certain lineage or within the whole family of Cyprinidae. From this perspective, HAmo SINE should provide useful phylogenetic makers for future analyses of the evolutionary relationships among species in the family Cyprinidae.

  8. Nocturnal Foraging by Red-Legged Kittiwakes, a Surface Feeding Seabird That Relies on Deep Water Prey During Reproduction.

    Science.gov (United States)

    Kokubun, Nobuo; Yamamoto, Takashi; Kikuchi, Dale M; Kitaysky, Alexander; Takahashi, Akinori

    2015-01-01

    Narrow foraging specialization may increase the vulnerability of marine predators to climate change. The red-legged kittiwake (Rissa brevirostris) is endemic to the Bering Sea and has experienced drastic population fluctuations in recent decades, presumably due to climate-driven changes in food resources. Red-legged kittiwakes are presumed to be a nocturnal surface-foraging seabird that feed almost entirely on deep water Myctophidae fishes. However, there is little empirical evidence confirming their nocturnal foraging activity during the breeding season. This study investigated the foraging behavior of red-legged kittiwakes by combining GPS tracking, accelerometry, and dietary analyses at the world's largest breeding colony of red-legged kittiwakes on St. George I. GPS tracking of 5 individuals revealed that 82.5% of non-flight behavior (including foraging and resting) occurred over the ocean basin (bottom depth >1,000 m). Acceleration data from 4 birds showed three types of behaviors during foraging trips: (1) flight, characterized by regular wing flapping, (2) resting on water, characterized by non-active behavior, and (3) foraging, when wing flapping was irregular. The proportions of both foraging and resting behaviors were higher at night (14.1 ± 7.1% and 20.8 ± 14.3%) compared to those during the day (6.5 ± 3.0% and 1.7 ± 2.7%). The mean duration of foraging (2.4 ± 2.9 min) was shorter than that of flight between prey patches (24.2 ± 53.1 min). Dietary analyses confirmed myctophids as the dominant prey (100% by occurrence and 98.4 ± 2.4% by wet-weight). Although the sample size was limited, these results suggest that breeding red-legged kittiwakes concentrated their foraging on myctophids available at the surface during nighttime in deep water regions. We propose that the diel patterns and ephemeral nature of their foraging activity reflected the availability of myctophids. Such foraging specialization may exacerbate the vulnerability of red-legged kittiwakes to climate change in the Bering Sea.

  9. Nocturnal Foraging by Red-Legged Kittiwakes, a Surface Feeding Seabird That Relies on Deep Water Prey During Reproduction.

    Directory of Open Access Journals (Sweden)

    Nobuo Kokubun

    Full Text Available Narrow foraging specialization may increase the vulnerability of marine predators to climate change. The red-legged kittiwake (Rissa brevirostris is endemic to the Bering Sea and has experienced drastic population fluctuations in recent decades, presumably due to climate-driven changes in food resources. Red-legged kittiwakes are presumed to be a nocturnal surface-foraging seabird that feed almost entirely on deep water Myctophidae fishes. However, there is little empirical evidence confirming their nocturnal foraging activity during the breeding season. This study investigated the foraging behavior of red-legged kittiwakes by combining GPS tracking, accelerometry, and dietary analyses at the world's largest breeding colony of red-legged kittiwakes on St. George I. GPS tracking of 5 individuals revealed that 82.5% of non-flight behavior (including foraging and resting occurred over the ocean basin (bottom depth >1,000 m. Acceleration data from 4 birds showed three types of behaviors during foraging trips: (1 flight, characterized by regular wing flapping, (2 resting on water, characterized by non-active behavior, and (3 foraging, when wing flapping was irregular. The proportions of both foraging and resting behaviors were higher at night (14.1 ± 7.1% and 20.8 ± 14.3% compared to those during the day (6.5 ± 3.0% and 1.7 ± 2.7%. The mean duration of foraging (2.4 ± 2.9 min was shorter than that of flight between prey patches (24.2 ± 53.1 min. Dietary analyses confirmed myctophids as the dominant prey (100% by occurrence and 98.4 ± 2.4% by wet-weight. Although the sample size was limited, these results suggest that breeding red-legged kittiwakes concentrated their foraging on myctophids available at the surface during nighttime in deep water regions. We propose that the diel patterns and ephemeral nature of their foraging activity reflected the availability of myctophids. Such foraging specialization may exacerbate the vulnerability of red-legged kittiwakes to climate change in the Bering Sea.

  10. Adaptation of the symbiotic Mesorhizobium-chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism.

    Science.gov (United States)

    Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, L S

    2016-08-09

    Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops.

  11. Design basis knowledge management for the newcomer countries. Relying on the owner/operator as a knowledgeable customer

    International Nuclear Information System (INIS)

    Lepouze, Benoît

    2013-01-01

    Becoming a knowledgeable customer is the first step to manage knowledge: • Vendors, consulting firms, TSOs can assist the future operator but it will remain the sole owner of the decisions; • Future owner operator has to become a knowledgeable customer: • Know what to ask for, • Know how to ask for it, • Know how to check if it got what it asked. • Where should knowledge management belong (management?, HRD?, procurement?) and is it important? What it means for DBKM ? (example): • The owner/operator (the licensee) is responsible in front of the safety agency: it should answer its questions at every stage of the program; • It will often turn back to its vendor/suppliers especially for detailed design questions; • But that means it has to know what to ask for and to check the result before talking to the regulator; • That also means it has to make sure knowledge is managed throughout the life of the program

  12. Self-control depletion in tufted capuchin monkeys (Sapajus spp.): does delay of gratification rely on a limited resource?

    Science.gov (United States)

    Petrillo, Francesca De; Gori, Emanuele; Truppa, Valentina; Ariely, Dan; Addessi, Elsa

    2015-01-01

    Self-control failure has enormous personal and societal consequences. One of the most debated models explaining why self-control breaks down is the Strength Model, according to which self-control depends on a limited resource. Either previous acts of self-control or taking part in highly demanding cognitive tasks have been shown to reduce self-control, possibly due to a reduction in blood glucose levels. However, several studies yielded negative findings, and recent meta-analyses questioned the robustness of the depletion effect in humans. We investigated, for the first time, whether the Strength Model applies to a non-human primate species, the tufted capuchin monkey. We tested five capuchins in a self-control task (the Accumulation task) in which food items were accumulated within individual’s reach for as long as the subject refrained from taking them. We evaluated whether capuchins’ performance decreases: (i) when tested before receiving their daily meal rather than after consuming it (Energy Depletion Experiment), and (ii) after being tested in two tasks with different levels of cognitive complexity (Cognitive Depletion Experiment). We also tested, in both experiments, how implementing self-control in each trial of the Accumulation task affected this capacity within each session and/or across consecutive sessions. Repeated acts of self-control in each trial of the Accumulation task progressively reduced this capacity within each session, as predicted by the Strength Model. However, neither experiencing a reduction in energy level nor taking part in a highly demanding cognitive task decreased performance in the subsequent Accumulation task. Thus, whereas capuchins seem to be vulnerable to within-session depletion effects, to other extents our findings are in line with the growing body of studies that failed to find a depletion effect in humans. Methodological issues potentially affecting the lack of depletion effects in capuchins are discussed. PMID:26322001

  13. Can we rely on cancer mortality data? Checking the validity of cervical cancer mortality data for Slovenia

    International Nuclear Information System (INIS)

    Primic Zakelj, M.; Pompe Kirn, V.; Skrlec, F.; Selb, J.

    2001-01-01

    Background. Valid inference on cervical cancer mortality is very difficult since - on the basis of death certificates - it is not always possible to distinguish between cervix, corpus and unspecified uterine cancer deaths. Our aim was to estimate the extent to which cervical cancer as the official cause of death reflects the true mortality from cervical cancer in Slovenia. Material and methods. The data on 2245 deaths from cervix, corpus uteri, and uterus-unspecified cancers for the period 1985-1999 were linked to the Cancer Registry of Slovenia database from the mortality database of Slovenia. Results. Officially, in the period 1985-1999, there were 878 cervical cancer deaths. The comparison of these causes of death with the cancer sites registered in the Cancer Registry revealed that they include only 87.7% patients with a previous diagnosis of cervical cancer. Of 650 corpus uteri cancer deaths, 17. 1 % of patients were registered to have cervical cancer, and of 717 unspecified uterine cancer deaths, 31.4% were registered. Taking into account the correctly identified cervical cancer cases among cervical cancer deaths and misclassified cervical cancer deaths as corpus uteri and unspecified uterine, the corrected number of deaths would be 1106. Conclusions. When evaluating the impact of cervical cancer mortality from national mortality rates, the stated underestimation should be taken into account. However, this does not hold for some other cancers. (author)

  14. Design of a Simple and Modular 2-DOF Ankle Physiotherapy Device Relying on a Hybrid Serial-Parallel Robotic Architecture

    Directory of Open Access Journals (Sweden)

    Christos E. Syrseloudis

    2011-01-01

    Full Text Available The aim of this work is to propose a new 2-DOF robotic platform with hybrid parallel-serial structure and to undertake its parametric design so that it can follow the whole range of ankle related foot movements. This robot can serve as a human ankle rehabilitation device. The existing ankle rehabilitation devices present typically one or more of the following shortcomings: redundancy, large size, or high cost, hence the need for a device that could offer simplicity, modularity, and low cost of construction and maintenance. In addition, our targeted device must be safe during operation, disallow undesirable movements of the foot, while adaptable to any human foot. Our detailed study of foot kinematics has led us to a new hybrid architecture, which strikes a balance among all aforementioned goals. It consists of a passive serial kinematics chain with two adjustable screws so that the axes of the chain match the two main ankle-axes of typical feet. An active parallel chain, which consists of two prismatic actuators, provides the movement of the platform. Thus, the platform can follow the foot movements, thanks to the passive chain, and also possesses the advantages of parallel robots, including rigidity, high stiffness and force capabilities. The lack of redundancy yields a simpler device with lower size and cost. The paper describes the kinematics modelling of the platform and analyses the force and velocity transmission. The parametric design of the platform is carried out; our simulations confirm the platform's suitability for ankle rehabilitation.

  15. Joint ownership of spouses and good faith acquisition of immovables by relying in the real estate cadastre

    Directory of Open Access Journals (Sweden)

    Cvetić Radenka M.

    2016-01-01

    Full Text Available The paper examines the rules on transferring of immovables in the matrimonial ownership regime against the backdrop of general notion of joint ownership and joint ownership (property of spouses. It explores whether the party who invokes the principle of reliance in the real estate cadastre shall be protected in the absence of an explicit rule guaranteeing the protection of a good faith acquirer in case of an unauthoriesd transfer done by one of the spouses. In other words, should for the sake of protection of confidence in legal transactions, acquisition of ownership and other rights in rem exceptionally be allowed by the good faith acquirer, provided that general presumptions under which confidence in accuracy and completeness of public registry of rights on immovables are fulfilled, in case where ownership was not inscribed as a joint ownership. The answer has been given in the absence of general rules on joint ownership, taking into account existing rules in the neighbouring countries, principle of reliance in the real estate cadastre and with due regard to the stance taken by the highest judicial body in the Republic of Serbia. The conclusion is that a spouse who is not inscribed in the public registry should not benefit from the protection against the good faith acquirer.

  16. Effect of arbuscular mycorrhizal and bacterial inocula on nitrate concentration in mesocosms simulating a wastewater treatment system relying on phytodepuration.

    Science.gov (United States)

    Lingua, Guido; Copetta, Andrea; Musso, Davide; Aimo, Stefania; Ranzenigo, Angelo; Buico, Alessandra; Gianotti, Valentina; Osella, Domenico; Berta, Graziella

    2015-12-01

    High nitrogen concentration in wastewaters requires treatments to prevent the risks of eutrophication in rivers, lakes and coastal waters. The use of constructed wetlands is one of the possible approaches to lower nitrate concentration in wastewaters. Beyond supporting the growth of the bacteria operating denitrification, plants can directly take up nitrogen. Since plant roots interact with a number of soil microorganisms, in the present work we report the monitoring of nitrate concentration in macrocosms with four different levels of added nitrate (0, 30, 60 and 90 mg l(-1)), using Phragmites australis, inoculated with bacteria or arbuscular mycorrhizal fungi, to assess whether the use of such inocula could improve wastewater denitrification. Higher potassium nitrate concentration increased plant growth and inoculation with arbuscular mycorrhizal fungi or bacteria resulted in larger plants with more developed root systems. In the case of plants inoculated with arbuscular mycorrhizal fungi, a faster decrease of nitrate concentration was observed, while the N%/C% ratio of the plants of the different treatments remained similar. At 90 mg l(-1) of added nitrate, only mycorrhizal plants were able to decrease nitrate concentration to the limits prescribed by the Italian law. These data suggest that mycorrhizal and microbial inoculation can be an additional tool to improve the efficiency of denitrification in the treatment of wastewaters via constructed wetlands.

  17. Method to mosaic gratings that relies on analysis of far-field intensity patterns in two wavelengths

    Science.gov (United States)

    Hu, Yao; Zeng, Lijiang; Li, Lifeng

    2007-01-01

    We propose an experimental method to coherently mosaic two planar diffraction gratings. The method uses a Twyman-Green interferometer to guarantee the planar parallelism of the two sub-aperture gratings, and obtains the in-plane rotational error and the two translational errors from analysis of the far-field diffraction intensity patterns in two alignment wavelengths. We adjust the relative attitude and position of the two sub-aperture gratings to produce Airy disk diffraction patterns in both wavelengths. In our experiment, the repeatability of in-plane rotation adjustment was 2.35 μrad and that of longitudinal adjustment was 0.11 μm. The accuracy of lateral adjustment was about 2.9% of the grating period.

  18. Argot2: a large scale function prediction tool relying on semantic similarity of weighted Gene Ontology terms.

    Science.gov (United States)

    Falda, Marco; Toppo, Stefano; Pescarolo, Alessandro; Lavezzo, Enrico; Di Camillo, Barbara; Facchinetti, Andrea; Cilia, Elisa; Velasco, Riccardo; Fontana, Paolo

    2012-03-28

    Predicting protein function has become increasingly demanding in the era of next generation sequencing technology. The task to assign a curator-reviewed function to every single sequence is impracticable. Bioinformatics tools, easy to use and able to provide automatic and reliable annotations at a genomic scale, are necessary and urgent. In this scenario, the Gene Ontology has provided the means to standardize the annotation classification with a structured vocabulary which can be easily exploited by computational methods. Argot2 is a web-based function prediction tool able to annotate nucleic or protein sequences from small datasets up to entire genomes. It accepts as input a list of sequences in FASTA format, which are processed using BLAST and HMMER searches vs UniProKB and Pfam databases respectively; these sequences are then annotated with GO terms retrieved from the UniProtKB-GOA database and the terms are weighted using the e-values from BLAST and HMMER. The weighted GO terms are processed according to both their semantic similarity relations described by the Gene Ontology and their associated score. The algorithm is based on the original idea developed in a previous tool called Argot. The entire engine has been completely rewritten to improve both accuracy and computational efficiency, thus allowing for the annotation of complete genomes. The revised algorithm has been already employed and successfully tested during in-house genome projects of grape and apple, and has proven to have a high precision and recall in all our benchmark conditions. It has also been successfully compared with Blast2GO, one of the methods most commonly employed for sequence annotation. The server is freely accessible at http://www.medcomp.medicina.unipd.it/Argot2.

  19. Adaptability of the Saccharomyces cerevisiae yeasts to wine fermentation conditions relies on their strong ability to consume nitrogen.

    Science.gov (United States)

    Brice, Claire; Cubillos, Francisco A; Dequin, Sylvie; Camarasa, Carole; Martínez, Claudio

    2018-01-01

    Saccharomyces cerevisiae strains are genetically diverse, largely as a result of human efforts to develop strains specifically adapted to various fermentation processes. These adaptive pressures from various ecological niches have generated behavioral differences among these strains, particularly in terms of their nitrogen consumption capacities. In this work, we characterize this phenotype by the specific quantity of nitrogen consumed under oenological fermentation conditions using a new approach. Indeed, unlike previous studies, our experiments were conducted in an environment containing excess nitrogen, eliminating the nitrogen limitation/starvation factor that is generally observed in fermentation processes. Using these conditions, we evaluated differences in the nitrogen consumption capacities for a set of five strains from diverse origins. The strains presented extremely different phenotypes and variations in their capacities to take up nitrogen from a wine fermentation environment. These variations reflect the differences in the nitrogen uptake capacities between wine and non-wine strains. Finally, the strains differed in their ability to adapt to the nitrogen composition of the environment, leading to variations in the cellular stress states, fermentation performances and the activity of the nitrogen sensing signaling pathway.

  20. Do political and economic choices rely on common neural substrates? A systematic review of the emerging neuropolitics literature

    Directory of Open Access Journals (Sweden)

    Sekoul eKrastev

    2016-02-01

    Full Text Available The methods of cognitive neuroscience are beginning to be applied to the study of political behavior. The neural substrates of value-based decision-making have been extensively examined in economic contexts; this might provide a powerful starting point for understanding political decision-making. Here, we asked to what extent the neuropolitics literature to date has used conceptual frameworks and experimental designs that make contact with the reward-related approaches that have dominated decision neuroscience. We then asked whether the studies of political behavior that can be considered in this light implicate the brain regions that have been associated with subjective value related to economic rewards. We performed a systematic literature review to identify papers addressing the neural substrates of political behavior and extracted the fMRI studies reporting behavioral measures of subjective value as defined in decision neuroscience studies of reward. A minority of neuropolitics studies met these criteria and relatively few brain activation foci from these studies overlapped with regions where activity has been related to subjective value. These findings show modest influence of reward-focused decision neuroscience on neuropolitics research to date. Whether the neural substrates of subjective value identified in economic choice paradigms generalize to political choice thus remains an open question. We argue that systematically addressing the commonalities and differences in these two classes of value-based choice will be important in developing a more comprehensive model of the brain basis of human decision-making.

  1. Do Political and Economic Choices Rely on Common Neural Substrates? A Systematic Review of the Emerging Neuropolitics Literature.

    Science.gov (United States)

    Krastev, Sekoul; McGuire, Joseph T; McNeney, Denver; Kable, Joseph W; Stolle, Dietlind; Gidengil, Elisabeth; Fellows, Lesley K

    2016-01-01

    The methods of cognitive neuroscience are beginning to be applied to the study of political behavior. The neural substrates of value-based decision-making have been extensively examined in economic contexts; this might provide a powerful starting point for understanding political decision-making. Here, we asked to what extent the neuropolitics literature to date has used conceptual frameworks and experimental designs that make contact with the reward-related approaches that have dominated decision neuroscience. We then asked whether the studies of political behavior that can be considered in this light implicate the brain regions that have been associated with subjective value related to "economic" reward. We performed a systematic literature review to identify papers addressing the neural substrates of political behavior and extracted the fMRI studies reporting behavioral measures of subjective value as defined in decision neuroscience studies of reward. A minority of neuropolitics studies met these criteria and relatively few brain activation foci from these studies overlapped with regions where activity has been related to subjective value. These findings show modest influence of reward-focused decision neuroscience on neuropolitics research to date. Whether the neural substrates of subjective value identified in economic choice paradigms generalize to political choice thus remains an open question. We argue that systematically addressing the commonalities and differences in these two classes of value-based choice will be important in developing a more comprehensive model of the brain basis of human decision-making.

  2. If the results of an article are noteworthy, read the entire article; do not rely on the abstract alone.

    Science.gov (United States)

    Dal-Ré, R; Castell, M V; García-Puig, J

    2015-11-01

    Clinicians typically update their knowledge by reading articles on the Internet. Easy access to the articles' abstracts and a lack of time to access other information sources creates a risk that therapeutic or diagnostic decisions will be made after reading just the abstracts. Occasionally, however, the abstracts of articles from clinical trials that have not obtained statistically significant differences in the primary study endpoint have reported other positive results, for example, of a secondary endpoint or a subgroup analysis. The article, however, correctly reports all results, including those of the primary endpoint. In the abstract, the safety information of the experimental treatment is usually deficient. The whole article should be read if a clinical decision is to be made. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  3. The walking-induced transient hack concept is valid & relies on a transient early-exercise hypoxemia.

    Directory of Open Access Journals (Sweden)

    Antoine Bruneau

    Full Text Available Decreased arterial oxygen pressure obtained at peak exercise is strong evidence of walking-induced hypoxemia, assuming that the lower pressure occurs just before exercise is stopped. Using empirical predefined models and transcutaneous oximetry, we have shown that some patients reporting exercise intolerance show a minimal value at the onset of walking and a post-exercise overshoot. These changes are referred to as transcutaneous "walking-induced transient hacks".In 245 patients, walking-induced transcutaneous oxygen pressure changes in the chest were analyzed using observer-independent clustering techniques. Clustering classes were compared to the profile types previously proposed with the cross-correlation technique. The classifications of patients according to both approaches were compared using kappa statistics. In 10 patients showing a hack on transcutaneous oximetry, we analyzed the results of direct iterative arterial sampling recorded during a new walking treadmill test.Clustering analysis resulted in 4 classes that closely fit the 4 most frequently proposed empirical models (cross-correlation coefficients: 0.93 to 0.97. The kappa between the two classifications was 0.865. In 10 patients showing transcutaneous hacks, the minimal direct arterial oxygen pressure value occurred at exercise onset, and these patients exhibited a recovery overshoot reaching a maximum at two minutes of recovery, confirming the walking-induced transient hypoxemia.In patients reporting exercise intolerance, transcutaneous oximetry could help to detect walking-induced transient hypoxemia, while peak-exercise arterial oximetry might be normal.

  4. Immigrant and Refugee Students across "Receiving" Nations: To What Extent Can Educators Rely on PISA for Answers?

    Science.gov (United States)

    Rubinstein-Avila, Eliane

    2016-01-01

    Massive population shift is a current global reality--especially given some of the latest development on European shores; some are calling it a humanitarian crisis. Although the United States (US) receives a large number of immigrants (documented and not) and about 70,000 refugees each year, it is certainly not the only nation to do so.…

  5. Termination of T cell priming relies on a phase of unresponsiveness promoting disengagement from APCs and T cell division.

    Science.gov (United States)

    Bohineust, Armelle; Garcia, Zacarias; Beuneu, Hélène; Lemaître, Fabrice; Bousso, Philippe

    2018-05-07

    T cells are primed in secondary lymphoid organs by establishing stable interactions with antigen-presenting cells (APCs). However, the cellular mechanisms underlying the termination of T cell priming and the initiation of clonal expansion remain largely unknown. Using intravital imaging, we observed that T cells typically divide without being associated to APCs. Supporting these findings, we demonstrate that recently activated T cells have an intrinsic defect in establishing stable contacts with APCs, a feature that was reflected by a blunted capacity to stop upon T cell receptor (TCR) engagement. T cell unresponsiveness was caused, in part, by a general block in extracellular calcium entry. Forcing TCR signals in activated T cells antagonized cell division, suggesting that T cell hyporesponsiveness acts as a safeguard mechanism against signals detrimental to mitosis. We propose that transient unresponsiveness represents an essential phase of T cell priming that promotes T cell disengagement from APCs and favors effective clonal expansion. © 2018 Bohineust et al.

  6. Catalytic ozonation not relying on hydroxyl radical oxidation: A selective and competitive reaction process related to metal-carboxylate complexes

    KAUST Repository

    Zhang, Tao; Croue, Jean-Philippe

    2014-01-01

    Catalytic ozonation following non-hydroxyl radical pathway is an important technique not only to degrade refractory carboxylic-containing organic compounds/matter but also to avoid catalyst deactivation caused by metal-carboxylate complexation

  7. Relying on satiety cues in food consumption : studies on the role of social context, appearance focus, and mindfulness

    NARCIS (Netherlands)

    Veer, van de E.

    2013-01-01

    Consumers eat at various sequential occasions throughout the day. The current thesis addresses the question of how one consumption episode can affect the amount of consumption at a subsequent episode. The thesis focuses specifically on how the social context during a consumption episode affects

  8. Interpersonal rejection results in increased appearance satisfaction for women who rely on body weight for self-worth.

    Science.gov (United States)

    O'Driscoll, Lauren M; Jarry, Josée L

    2015-01-01

    This study examined whether body weight contingent self-worth (BWCSW), the tendency to base self-worth on body weight, moderates the effects of interpersonal rejection on self-esteem and body satisfaction. In an online survey, female undergraduates (N=148) completed measures of trait self-esteem, depression, and BWCSW. In a subsequent lab session, participants were assigned to either an interpersonal rejection or to a neutral control condition, after which they completed measures of state self-esteem and body satisfaction. Compared to women with lower BWCSW, women with higher BWCSW reported lower appearance self-esteem (p=.001) and body satisfaction (p=.004) across conditions. However, they reacted to rejection by reporting greater appearance self-esteem (p=.034) and body satisfaction (p=.021). Rejection had no effect on women with lower BWCSW. The reaction of women with higher BWCSW is interpreted as a compensatory self-enhancement response to interpersonal rejection within a self-important domain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Do Political and Economic Choices Rely on Common Neural Substrates? A Systematic Review of the Emerging Neuropolitics Literature

    Science.gov (United States)

    Krastev, Sekoul; McGuire, Joseph T.; McNeney, Denver; Kable, Joseph W.; Stolle, Dietlind; Gidengil, Elisabeth; Fellows, Lesley K.

    2016-01-01

    The methods of cognitive neuroscience are beginning to be applied to the study of political behavior. The neural substrates of value-based decision-making have been extensively examined in economic contexts; this might provide a powerful starting point for understanding political decision-making. Here, we asked to what extent the neuropolitics literature to date has used conceptual frameworks and experimental designs that make contact with the reward-related approaches that have dominated decision neuroscience. We then asked whether the studies of political behavior that can be considered in this light implicate the brain regions that have been associated with subjective value related to “economic” reward. We performed a systematic literature review to identify papers addressing the neural substrates of political behavior and extracted the fMRI studies reporting behavioral measures of subjective value as defined in decision neuroscience studies of reward. A minority of neuropolitics studies met these criteria and relatively few brain activation foci from these studies overlapped with regions where activity has been related to subjective value. These findings show modest influence of reward-focused decision neuroscience on neuropolitics research to date. Whether the neural substrates of subjective value identified in economic choice paradigms generalize to political choice thus remains an open question. We argue that systematically addressing the commonalities and differences in these two classes of value-based choice will be important in developing a more comprehensive model of the brain basis of human decision-making. PMID:26941703

  10. Early CT perfusion mismatch in acute stroke is not time-dependent but relies on collateralization grade

    Energy Technology Data Exchange (ETDEWEB)

    Baumgarten, Louisa von; Straube, Andreas [University of Munich Hospitals, Department of Neurology, Munich (Germany); Thierfelder, Kolja M.; Beyer, Sebastian E.; Baumann, Alena B.; Bollwein, Christine; Reiser, Maximilian F.; Sommer, Wieland H. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Janssen, Hendrik [Ludwig-Maximilians-University Hospital Munich, Department of Neuroradiology, Munich (Germany)

    2016-04-15

    Factors that determine the extent of the penumbra in the initial diagnostic workup using whole brain CT Perfusion (WB-CTP) remain unclear. The purpose of the current study was to determine a possible dependency of the initial mismatch size between cerebral blood flow (CBF) and cerebral blood volume (CBV) from time after symptom onset, leptomeningeal collateralization, and occlusion localization in acute middle cerebral artery (MCA) infarctions. Out of an existing cohort of 992 consecutive patients receiving multiparametric CT scans including WB-CTP due to suspected stroke, we included patients who had (1) a witnessed time of symptom onset, (2) an infarction of the MCA territory as documented by follow-up imaging, and (3) an initial CBF volume of >10 ml. CBF and CBV lesion sizes, collateralization grade, and the site of occlusion were determined. We included 103 patients. Univariate analysis showed that time from symptom onset (168 +/- 91.2 min) did not correlate with relative or absolute mismatch volumes (p = 0.458 and p = 0.921). Higher collateralization gradings were associated with small absolute mismatch volumes (p = 0.004 and p < 0.001). Internal carotid artery (ICA) occlusions were associated with large absolute mismatch volumes (p = 0.004). Multivariate analysis confirmed that ICA occlusion was associated with large absolute mismatch volumes (p = 0.005), and high collateral grade was associated with small absolute mismatch volumes (p = 0.017). There is no significant correlation between initial CTP mismatch and time after symptom onset. Predictors of mismatch size include the extent of the collaterals and a proximal location of the occlusion. (orig.)

  11. We could learn much more from 1918 pandemic-the (mis)fortune of research relying on original death certificates.

    Science.gov (United States)

    Alonso, Wladimir J; Nascimento, Francielle C; Chowell, Gerardo; Schuck-Paim, Cynthia

    2018-05-01

    The analysis of historical death certificates has enormous potential for understanding how the health of populations was shaped by diseases and epidemics and by the implementation of specific interventions. In Brazil, the systematic archiving of mortality records was initiated only in 1944-hence the analysis of death registers before this time requires searching for these documents in public archives, notaries, parishes, and especially ancient cemeteries, which are often the only remaining source of information about these deaths. This article describes an effort to locate original death certificates in Brazil and document their organization, accessibility, and preservation. To this end, we conducted an exploratory study in 19 of the 27 Brazilian states, focusing on the period surrounding the 1918 influenza pandemic (1913-1921). We included 55 cemeteries, 22 civil archives, and one military archive. Apart from few exceptions, the results show the absence of a curatorial policy for the organization, access or even physical preservation of this material, frequently leading to unavailability, deterioration, and ultimately its complete loss. This study indicates the need to promote the preservation of a historical heritage that is a key to understanding historical epidemiological patterns and human responses to global health threats. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. So you want to work? What employers say about job skills, recruitment and hiring employees who rely on AAC.

    Science.gov (United States)

    Bryen, Diane Nelson; Potts, Blyden B; Carey, Allison C

    2007-06-01

    In order to better understand employer perspectives with respect to hiring and working with people who use AAC and the kinds of employment barriers they believe exist for these individuals, a study into the job requirements, recruitment processes, and hiring processes of 27 employers in the United States was conducted. Interviews with the 27 employers focused on 48 jobs in 25 unique categories, many of which had previously been identified as desirable by 38 adults who used AAC (some of whom were employed and some of whom were seeking employment). Findings suggest that, while level of education is still important to employers, skills such as time management, problem solving, communication, use of an understandable and standard voice, and basic technology may be even more so. The study also found that having an effective job-related network is important, as is the ability to provide credible references and do well during in-person interviews with potential employers.

  13. Development of a millimetrically scaled biodiesel transesterification device that relies on droplet-based co-axial fluidics

    Science.gov (United States)

    Yeh, S. I.; Huang, Y. C.; Cheng, C. H.; Cheng, C. M.; Yang, J. T.

    2016-07-01

    In this study, we investigated a fluidic system that adheres to new concepts of energy production. To improve efficiency, cost, and ease of manufacture, a millimetrically scaled device that employs a droplet-based co-axial fluidic system was devised to complete alkali-catalyzed transesterification for biodiesel production. The large surface-to-volume ratio of the droplet-based system, and the internal circulation induced inside the moving droplets, significantly enhanced the reaction rate of immiscible liquids used here - soybean oil and methanol. This device also decreased the molar ratio between methanol and oil to near the stoichiometric coefficients of a balanced chemical equation, which enhanced the total biodiesel volume produced, and decreased the costs of purification and recovery of excess methanol. In this work, the droplet-based co-axial fluidic system performed better than other methods of continuous-flow production. We achieved an efficiency that is much greater than that of reported systems. This study demonstrated the high potential of droplet-based fluidic chips for energy production. The small energy consumption and low cost of the highly purified biodiesel transesterification system described conforms to the requirements of distributed energy (inexpensive production on a moderate scale) in the world.

  14. Polyploid species rely on vegetative reproduction more than diploids: a re-examination of the old hypothesis

    Czech Academy of Sciences Publication Activity Database

    Herben, Tomáš; Suda, Jan; Klimešová, Jitka

    2017-01-01

    Roč. 120, č. 2 (2017), s. 341-349 ISSN 0305-7364 R&D Projects: GA ČR(CZ) GA16-19245S Institutional support: RVO:67985939 Keywords : phylogenetic analysis * clonal traits * correlated evolution Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 4.041, year: 2016

  15. Catalytic ozonation of oxalate with a cerium supported palladium oxide: An efficient degradation not relying on hydroxyl radical oxidation

    KAUST Repository

    Zhang, Tao

    2011-11-01

    The cerium supported palladium oxide (PdO/CeO 2) at a low palladium loading was found very effective in catalytic ozonation of oxalate, a probe compound that is difficult to be efficiently degraded in water with hydroxyl radical oxidation and one of the major byproducts in ozonation of organic matter. The oxalate was degraded into CO 2 during the catalytic ozonation. The molar ratio of oxalate degraded to ozone consumption increased with increasing catalyst dose and decreasing ozone dosage and pH under the conditions of this study. The maximum molar ratio reached around 1, meaning that the catalyst was highly active and selective for oxalate degradation in water. The catalytic ozonation, which showed relatively stable activity, does not promote hydroxyl radical generation from ozone. Analysis with ATR-FTIR and in situ Raman spectroscopy revealed that 1) oxalate was adsorbed on CeO 2 of the catalyst forming surface complexes, and 2) O 3 was adsorbed on PdO of the catalyst and further decomposed to surface atomic oxygen (*O), surface peroxide (*O 2), and O 2 gas in sequence. The results indicate that the high activity of the catalyst is related to the synergetic function of PdO and CeO 2 in that the surface atomic oxygen readily reacts with the surface cerium-oxalate complex. This kind of catalytic ozonation would be potentially effective for the degradation of polar refractory organic pollutants and hydrophilic natural organic matter. © 2011 American Chemical Society.

  16. Number and density discrimination rely on a common metric: Similar psychophysical effects of size, contrast, and divided attention.

    Science.gov (United States)

    Tibber, Marc S; Greenwood, John A; Dakin, Steven C

    2012-06-04

    While observers are adept at judging the density of elements (e.g., in a random-dot image), it has recently been proposed that they also have an independent visual sense of number. To test the independence of number and density discrimination, we examined the effects of manipulating stimulus structure (patch size, element size, contrast, and contrast-polarity) and available attentional resources on both judgments. Five observers made a series of two-alternative, forced-choice discriminations based on the relative numerosity/density of two simultaneously presented patches containing 16-1,024 Gaussian blobs. Mismatches of patch size and element size (across reference and test) led to bias and reduced sensitivity in both tasks, whereas manipulations of contrast and contrast-polarity had varied effects on observers, implying differing strategies. Nonetheless, the effects reported were consistent across density and number judgments, the only exception being when luminance cues were made available. Finally, density and number judgment were similarly impaired by attentional load in a dual-task experiment. These results are consistent with a common underlying metric to density and number judgments, with the caveat that additional cues may be exploited when they are available.

  17. Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

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    Côté Claude H

    2011-10-01

    Full Text Available Abstract Background Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2. The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade. Methods Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF2α production. Proliferation assays were also performed in presence of different prostaglandins (PGs. Results Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor in vivo in skeletal muscle cells and in satellite cells and in vitro in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-12,14-prostaglandin J2 (15Δ-PGJ2, a product of COX-2-derived prostaglandin D2, stimulated myoblast proliferation, but not PGE2 and PGF2α. Conclusions Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.

  18. A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis.

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    Hirofumi Nakaoka

    Full Text Available Genome-wide association studies (GWAS have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA. Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate

  19. A Single-Nucleotide Polymorphism in Serine-Threonine Kinase 11, the Gene Encoding Liver Kinase B1, Is a Risk Factor for Multiple Sclerosis

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    Anne I. Boullerne

    2015-02-01

    Full Text Available We identified a family in which five siblings were diagnosed with multiple sclerosis (MS or clinically isolated syndrome. Several women in the maternal lineage have comorbidities typically associated with Peutz Jeghers Syndrome, a rare autosomal-dominant disease caused by mutations in the serine-threonine-kinase 11 (STK11 gene, which encodes liver kinase B1. Sequence analysis of DNA from one sibling identified a single-nucleotide polymorphism (SNP within STK11 intron 5. This SNP (dbSNP ID: rs9282860 was identified by TaqMan polymerase chain reaction (PCR assays in DNA samples available from two other siblings. Further screening was carried out in samples from 654 relapsing-remitting MS patients, 100 primary progressive MS patients, and 661 controls. The STK11-SNP has increased frequency in all female patients versus controls (odds ratio = 1.66, 95% CI = 1.05, 2.64, p = .032. The STK11-SNP was not associated with disease duration or onset; however, it was significantly associated with reduced severity (assessed by MS severity scores, with the lowest scores in patients who also harbored the HLA-DRB1*1501 allele. In vitro studies showed that peripheral blood mononuclear cells from members of the family were more sensitive to the mitochondrial inhibitor metformin than cells from MS patients with the major STK11 allele. The increased association of SNP rs9282860 in women with MS defines this variant as a genetic risk factor. The lower disease severity observed in the context of HLA-DRB1*1501 combined with limited in vitro studies raises the provocative possibility that cells harboring the STK11-SNP could be targeted by drugs which increase metabolic stress.

  20. Using high-resolution human leukocyte antigen typing of 11,423 randomized unrelated individuals to determine allelic varieties, deduce probable human leukocyte antigen haplotypes, and observe linkage disequilibria between human leukocyte antigen-B and-C and human leukocyte antigen-DRB1 and-DQB1 alleles in the Taiwanese Chinese population

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    Kuo-Liang Yang

    2017-01-01

    Full Text Available Objective: We report here the human leukocyte antigen (HLA allelic variety and haplotype composition in a cohort of the Taiwanese Chinese population and their patterns of linkage disequilibria on HLA-B: HLA-C alleles and HLA-DRB1: HLA-DQB1 alleles at a high-resolution level. Materials and Methods: Peripheral whole blood from 11,423 Taiwanese Chinese unrelated individuals was collected in acid citrate dextrose. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit. The DNA material was subjected to HLA genotyping for HLA-A,-B,-C,-DRB1, and-DQB1 loci using a commercial polymerase chain reaction-sequence-based typing (PCR-SBT kit, the SeCore® A/B/C/DRB1/DQB1 Locus Sequencing kit. High-resolution allelic sequencing was performed as previously described. Results: The number of individual HLA-B alleles detected was greater than the number of alleles recognized in the both the HLA-A and-DRB1 loci. Several novel alleles were discovered as a result of employing the SBT method and the high number of donors tested. In addition, we observed a genetic polymorphic feature of association between HLA-A and-B, HLA-B and-C, and HLA-DRB1 and-DQB1 alleles. Further, the homozygous haplotype frequencies of HLA-A and-B; HLA-A,-C, and-B; HLA-A,-C,-B, and-DRB1; and HLA-A,-C,-B,-DRB1, and-DQB1 in Taiwanese Chinese population are presented. Conclusion: As increasing number of HLA alleles are being discovered, periodic HLA profile investigation in a given population is essential to recognize the HLA complexity in that population. Population study can also provide an up-to-date strategic plan for future needs in terms of compatibility measurement for HLA matching between transplant donors and patients.

  1. Distribution of Human Leukocyte Antigen alleles in Systemic Lupus Erythematosus patients with Angiotensin Converting Enzyme Insertion/Deletion Polymorphism

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    Nageen Hussain

    2013-02-01

    Full Text Available Systemic Lupus Erythematosus is one of the classic examples of autoimmune diseases among human beings and is a rare disease in Pakistani population. Clinically it is a quite diverse and complicated autoimmune disease in a sense that it involves multiple organs of the body and mimics with other diseases as well. This study focused on the distribution of HLA alleles in SLE patients with ACE I/D Polymorphism. A total of 122 individuals were enrolled in this study, 61 were the SLE patients who fulfilled revised ACR criteria and 61 were the healthy controls. Mean age of SLE patients at diagnosis was 30.35 ± 1.687 years (12-68 years. ACE gene I/D polymorphism was performed by nested PCR and DNA based HLA typing technique was used. ACE gene I/D polymorphism of Intron16 was studied and found to be involved in the activity of SLE. There is high frequency of HLA-A*01, HLA-B*40, HLA-DRB1*01 alleles in SLE patients with ACE DD genotype. The distribution of HLA-A, -B, -DRB1 alleles was analyzed in SLE patients with various disease phenotypes. HLA-A*01 and HLA-B*40 was the most common allele found in SLE patients with the involvement of skin. HLA-A*01, -A*03, HLA-B*13 and -B*46 were common in SLE patients with arthritis while HLA-A*26 and -A*69 were commonly found in Lupus nephritis cases. SLE patients involving both skin and kidney had an allele HLA-DRB1*01 common in them.

  2. Characteristics of Japanese inflammatory bowel disease susceptibility loci.

    Science.gov (United States)

    Arimura, Yoshiaki; Isshiki, Hiroyuki; Onodera, Kei; Nagaishi, Kanna; Yamashita, Kentaro; Sonoda, Tomoko; Matsumoto, Takayuki; Takahashi, Atsushi; Takazoe, Masakazu; Yamazaki, Keiko; Kubo, Michiaki; Fujimiya, Mineko; Imai, Kohzoh; Shinomura, Yasuhisa

    2014-08-01

    There are substantial differences in inflammatory bowel disease (IBD) genetics depending on the populations examined. We aimed to identify Japanese population-specific or true culprit susceptibility genes through a meta-analysis of past genetic studies of Japanese IBD. For this study, we reviewed 2,703 articles. The review process consisted of three screening stages: we initially searched for relevant studies and then relevant single nucleotide polymorphisms (SNPs). Finally, we adjusted them for the meta-analysis. To maximize our chances of analysis, we introduced proxy SNPs during the first stage. To minimize publication bias, no significant SNPs and solitary SNPs without pairs were combined to be reconsidered during the third stage. Additionally, two SNPs were newly genotyped. Finally, we conducted a meta-analysis of 37 published studies in 50 SNPs located at 22 loci corresponding to the total number of 4,853 Crohn's disease (CD), 5,612 ulcerative colitis (UC) patients, and 14,239 healthy controls. We confirmed that the NKX2-3 polymorphism is associated with common susceptibility to IBD and that HLA-DRB1*0450 alleles increase susceptibility to CD but reduce risk for UC while HLA-DRB1*1502 alleles increase susceptibility to UC but reduce CD risk. Moreover, we found individual disease risk loci: TNFSF15 and TNFα to CD and HLA-B*5201, and NFKBIL1 to UC. The genetic risk of HLA was substantially high (odds ratios ranged from 1.54 to 2.69) while that of common susceptibility loci to IBD was modest (odds ratio ranged from 1.13 to 1.24). Results indicate that Japanese IBD susceptibility loci identified by the meta-analysis are closely associated with the HLA regions.

  3. Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Leal, Bárbara; Chaves, João; Carvalho, Cláudia; Bettencourt, Andreia; Brito, Cláudia; Boleixa, Daniela; Freitas, Joel; Brás, Sandra; Lopes, João; Ramalheira, João; Costa, Paulo P; da Silva, Berta Martins; da Silva, António Martins

    2018-04-01

    Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1β and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1β), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case-control study. The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13-4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1β levels produced by this genotype. High IL-1β levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.

  4. Eosinophilic granulomatosis with polyangiitis: an overview

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    Andrea eGioffredi

    2014-11-01

    Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA is a multisystemic disorder, belonging to the small vessel ANCA-associated vasculitis, defined as a eosinophil-rich and necrotizing granulomatous inflammation often involving the respiratory tract, and necrotizing vasculitis predominantly affecting small to medium-sized vessels, associated with asthma and eosinophilia. EGPA pathogenesis is not well known: HLA-DRB1*04 and *07, HLA-DRB4 and IL10.2 haplotype of the IL-10 promoter gene are the most studied genetic determinants. Among the acquired pathogenetic factors, the exposure to different allergens, infections, vaccinations, drugs and silica exposure have been involved.Eosinophils are the most characteristic cells in EGPA and different studies have demonstrated their role as effector and immunoregulatory cells.EGPA is considered a disease with a prevalent activation of the Th2 cellular-mediated inflammatory response but also humoral immunity plays an important role. A link between B and T inflammatory responses may explain different disease features. EGPA typically develops into three sequential phases: the allergic phase, distinguished by the occurrence of asthma, allergic rhinitis and sinusitis, the eosinophilic phase, in which the main pathological finding is the eosinophilic organ infiltrations (e.g. lungs, heart and gastrointestinal system and the vasculitic phase, characterized by purpura, peripheral neuropathy and constitutional symptoms.ANCA (especially pANCA anti-MPO are present in 40-60% of the patients. An elevation of IgG4 is frequently found. Corticosteroids and cyclophosphamide are classically used for remission induction, while azathioprine and methotrexate are the therapeutic options for remission maintenance. B-cell depletion with rituximab has shown promising results for remission induction.

  5. Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

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    Mqondisi Tshabalala

    2018-01-01

    Full Text Available Human leukocyte antigen- (HLA- A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR. Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096, B∗07:02g (0.082, C∗07:02g (0.180, DQB1∗06:02 (0.157, and DRB1∗15:01 (0.072. The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067, which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.

  6. Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

    Science.gov (United States)

    de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

    2014-08-01

    Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders.

    Science.gov (United States)

    Ben Hamad, M; Cornelis, F; Mbarek, H; Chabchoub, G; Marzouk, S; Bahloul, Z; Rebai, A; Fakhfakh, F; Ayadi, H; Petit-Teixeira, E; Maalej, A

    2011-01-01

    The signal transducer and activator of transcription 4 (STAT4) gene localised on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. The aim of this study was to investigate the role of the STAT4 gene in susceptibility to rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) in Tunisian case control studies. Genotyping of STAT4 rs7574865 single nucleotide polymorphism (SNP) was performed in 140 patients affected with RA, 159 patients affected with AITDs and 200 healthy controls using TaqMan® allelic discrimination assay. Data were analysed by χ2-test, genotype relative risk (GRR) and odds ratio (OR). Our results revealed that frequencies of the T allele and the T/T genotype were significantly higher among RA patients compared to controls (p=0.008; p=0.003, respectively). However, no significant associations with the risk of autoimmune thyroid diseases were detected. Moreover, the stratification of RA patients subgroups revealed a significant association of both T allele and T/T genotype in patients presented erosion (p=0.003; p=0.004, respectively) as well as anti-cyclic peptides-negative RA (ACPA-) (p=0.002; p=0.0003, respectively). Furthermore, genotypic association was found according to the absence of rheumatoid factor antibody (RF) (p=0.0014). But, no significant differences in allele and genotype frequencies of STAT4 rs7574865 polymorphism were detected according to the presence of another autoimmune disease, nodules and in HLA-DRB1*04 and HLA-DRB1*0404 positive subgroups. Our results support involvement of the STAT4 gene in the genetic susceptibility to RA but not to AITDs in the Tunisian population.

  8. A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33.2.

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    Monica Chang

    2008-06-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (OR(common = 1.28, trend P(comb = 1.45E-06. Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (P(comb 5.41E-09. The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential.

  9. 76 FR 20392 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

    Science.gov (United States)

    2011-04-12

    ..., SMH, SNDK, SPLS, SPXU, SPY, SSO, SYMC, TBT, T, TLT, TNA,TSM, TWM, TXN, TZA, UCO, USO, UWM, UYG, VALE..., S, SH, SLV, SPF, SPXU, SPY, SSO, TBT, TLT, TWM, TZA, UCO, USO, UWM, VXX, XLI, XLP. Transactions in...

  10. STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE SINGLE-STRAND ORIGIN OF REPLICATION FROM THE LACTOCOCCAL PLASMID PWVO1

    NARCIS (Netherlands)

    SEEGERS, JFML; ZHAO, AC; MEIJER, WJJ; KHAN, SA; VENEMA, G; BRON, S

    1995-01-01

    The single-strand origin (SSO) of the rolling-circle (RC), broad-host-range lactococcal plasmid pWVO1 was functionally characterized. The activity of this SSO in the conversion of single-stranded DNA to double-stranded DNA was tested both in vivo and in vitro. In addition, the effect of this SSO on

  11. SV-BR-1-GM, a Clinically Effective GM-CSF-Secreting Breast Cancer Cell Line, Expresses an Immune Signature and Directly Activates CD4+ T Lymphocytes

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    Markus D. Lacher

    2018-05-01

    Full Text Available Targeted cancer immunotherapy with irradiated, granulocyte–macrophage colony-stimulating factor (GM-CSF-secreting, allogeneic cancer cell lines has been an effective approach to reduce tumor burden in several patients. It is generally assumed that to be effective, these cell lines need to express immunogenic antigens coexpressed in patient tumor cells, and antigen-presenting cells need to take up such antigens then present them to patient T cells. We have previously reported that, in a phase I pilot study (ClinicalTrials.gov NCT00095862, a subject with stage IV breast cancer experienced substantial regression of breast, lung, and brain lesions following inoculation with clinical formulations of SV-BR-1-GM, a GM-CSF-secreting breast tumor cell line. To identify diagnostic features permitting the prospective identification of patients likely to benefit from SV-BR-1-GM, we conducted a molecular analysis of the SV-BR-1-GM cell line and of patient-derived blood, as well as a tumor specimen. Compared to normal human breast cells, SV-BR-1-GM cells overexpress genes encoding tumor-associated antigens (TAAs such as PRAME, a cancer/testis antigen. Curiously, despite its presumptive breast epithelial origin, the cell line expresses major histocompatibility complex (MHC class II genes (HLA-DRA, HLA-DRB3, HLA-DMA, HLA-DMB, in addition to several other factors known to play immunostimulatory roles. These factors include MHC class I components (B2M, HLA-A, HLA-B, ADA (encoding adenosine deaminase, ADGRE5 (CD97, CD58 (LFA3, CD74 (encoding invariant chain and CLIP, CD83, CXCL8 (IL8, CXCL16, HLA-F, IL6, IL18, and KITLG. Moreover, both SV-BR-1-GM cells and the responding study subject carried an HLA-DRB3*02:02 allele, raising the question of whether SV-BR-1-GM cells can directly present endogenous antigens to T cells, thereby inducing a tumor-directed immune response. In support of this, SV-BR-1-GM cells (which also carry the HLA-DRB3*01:01 allele treated with

  12. Determinación de HLA en pacientes con Síndrome de Parry Romberg atendidos en el Servicio de Cirugía Plástica y Reconstructiva del Hospital General "Dr. Manuel Gea González"

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    Damián Palafox

    Full Text Available Introducción y Objetivo. El síndrome de Parry Romberg se caracteriza por atrofia hemifacial progresiva; afecta piel y tejidos blandos y en ocasiones provoca también atrofia de músculos, cartílago y estructuras óseas subyacentes. Su diagnóstico diferencial incluye: esclerodermia generalizada, morfea y síndrome de CREST. Las alteraciones en piel se asocian con variantes alélicas (polimórficas del sistema HLA (antígeno leucocitario humano. La esclerodermia se ha asociado con HLA DR11, el CREST con DR1 y DR3, en tanto que la morfea no parece asociarse a genes del HLA en población mexicana. El propósito de este trabajo es explorar la posibilidad de asociación del síndrome de Parry Romberg con algún alelo del sistema HLA con el fin de entender el mecanismo fisiopatogénico y el probable papel de la etnicidad en la prevalencia e incidencia de esta enfermedad en individuos mestizos mexicanos. Material y método. Estudiamos 24 pacientes con Parry Romberg, de la consulta externa de Cirugía Plástica y Reconstructiva del Hospital General "Dr. Manuel Gea González" de la Ciudad de México. El diagnóstico se basó en hallazgos clínicos, imagenología e histopatología de las lesiones dérmicas. Establecimos las frecuencias génicas y haplotípicas de los antígenos del sistema HLA en los 24 pacientes (48 haplotipos. El estudio incluyó los loci HLA A, B, DR, DQ. Comparamos los resultados con las frecuencias presentes en un grupo de 99 controles mestizos mexicanos sin antecedentes de enfermedades autoinmunes y/o metabólicas. Analizamos las diferencias en las frecuencias génicas mediante estadística no paramétrica que incluyó prueba de Chi cuadrado y exacta de Fisher, además de determinación de RM (razón de momios e intervalos de confianza de 95%. Resultados. Encontramos en los pacientes con Parry Romberg aumento significativo del HLA DRB1*16 (frecuencia génica: 14% en SPR vs 1% en normales. p=0.002, OR: 6.5, IC 95%: 1.9-21.7 y

  13. Identification and location tasks rely on different mental processes: a diffusion model account of validity effects in spatial cueing paradigms with emotional stimuli.

    Science.gov (United States)

    Imhoff, Roland; Lange, Jens; Germar, Markus

    2018-02-22

    Spatial cueing paradigms are popular tools to assess human attention to emotional stimuli, but different variants of these paradigms differ in what participants' primary task is. In one variant, participants indicate the location of the target (location task), whereas in the other they indicate the shape of the target (identification task). In the present paper we test the idea that although these two variants produce seemingly comparable cue validity effects on response times, they rest on different underlying processes. Across four studies (total N = 397; two in the supplement) using both variants and manipulating the motivational relevance of cue content, diffusion model analyses revealed that cue validity effects in location tasks are primarily driven by response biases, whereas the same effect rests on delay due to attention to the cue in identification tasks. Based on this, we predict and empirically support that a symmetrical distribution of valid and invalid cues would reduce cue validity effects in location tasks to a greater extent than in identification tasks. Across all variants of the task, we fail to replicate the effect of greater cue validity effects for arousing (vs. neutral) stimuli. We discuss the implications of these findings for best practice in spatial cueing research.

  14. Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

    Science.gov (United States)

    Husein-ElAhmed, Husein

    2018-03-01

    The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (Pbasal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell carcinomas in early stages. As a distinct entity, sclerodermiform basal cell carcinomas show a lack of early diagnosis compared to less-aggressive subtypes of BCC, and thus, more accurate diagnostic tools apart from dermatoscopy are required to reach the goal of early-stage diagnosis of sclerodermiform basal cell carcinomas.

  15. Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

    NARCIS (Netherlands)

    L.Y.A. Chai (Louis); F. van de Veerdonk (Frank); R.J. Marijnissen (Renoud); S.C. Cheng (Shih-Chin); A.L. Khoo; M. Hectors (Magda); K. Lagrou (Katrien); A.G. Vonk (Alieke); J. Maertens (Johan); L.A.B. Joosten (Leo); B.J. Kullberg (Bart Jan); M.G. Netea (Mihai)

    2010-01-01

    textabstractSummary Both interferon-γ-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the

  16. Short-term retention of a single word relies on retrieval from long-term memory when both rehearsal and refreshing are disrupted.

    Science.gov (United States)

    Rose, Nathan S; Buchsbaum, Bradley R; Craik, Fergus I M

    2014-07-01

    Many working memory (WM) models propose that the focus of attention (or primary memory) has a capacity limit of one to four items, and therefore, that performance on WM tasks involves retrieving some items from long-term (or secondary) memory (LTM). In the present study, we present evidence suggesting that recall of even one item on a WM task can involve retrieving it from LTM. The WM task required participants to make a deep (living/nonliving) or shallow ("e"/no "e") level-of-processing (LOP) judgment on one word and to recall the word after a 10-s delay on each trial. During the delay, participants either rehearsed the word or performed an easy or a hard math task. When the to-be-remembered item could be rehearsed, recall was fast and accurate. When it was followed by a math task, recall was slower, error-prone, and benefited from a deeper LOP at encoding, especially for the hard math condition. The authors suggest that a covert-retrieval mechanism may have refreshed the item during easy math, and that the hard math condition shows that even a single item cannot be reliably held in WM during a sufficiently distracting task--therefore, recalling the item involved retrieving it from LTM. Additionally, performance on a final free recall (LTM) test was better for items recalled following math than following rehearsal, suggesting that initial recall following math involved elaborative retrieval from LTM, whereas rehearsal did not. The authors suggest that the extent to which performance on WM tasks involves retrieval from LTM depends on the amounts of disruption to both rehearsal and covert-retrieval/refreshing maintenance mechanisms.

  17. Should We Stop Developing Heuristics and Only Rely on Mixed Integer Programming Solvers in Automated Test Assembly? A Rejoinder to van der Linden and Li (2016).

    Science.gov (United States)

    Chen, Pei-Hua

    2017-05-01

    This rejoinder responds to the commentary by van der Linden and Li entiled "Comment on Three-Element Item Selection Procedures for Multiple Forms Assembly: An Item Matching Approach" on the article "Three-Element Item Selection Procedures for Multiple Forms Assembly: An Item Matching Approach" by Chen. Van der Linden and Li made a strong statement calling for the cessation of test assembly heuristics development, and instead encouraged embracing mixed integer programming (MIP). This article points out the nondeterministic polynomial (NP)-hard nature of MIP problems and how solutions found using heuristics could be useful in an MIP context. Although van der Linden and Li provided several practical examples of test assembly supporting their view, the examples ignore the cases in which a slight change of constraints or item pool data might mean it would not be possible to obtain solutions as quickly as before. The article illustrates the use of heuristic solutions to improve both the performance of MIP solvers and the quality of solutions. Additional responses to the commentary by van der Linden and Li are included.

  18. The International System on Occupational Exposure. An ALARA Success Story Relying on Strong Individual Commitments, Effective International Feedback and Exchanges, and a Robust Database - 20 years of progress

    International Nuclear Information System (INIS)

    Lefaure, Christian; Doty, Richard

    2013-06-01

    Why, more than 20 years ago, did there emerge the need for an International System on Occupational Exposure (ISOE)? How was it created? What were the problems and their possible solutions? Who were the main stakeholders? These are a few of the questions that the ISOE NEA Secretariat and Bureau asked Christian Lefaure, ex CEPN Deputy Director, to address in preparing a report on the history of ISOE and its progress. He had been directly involved in the brainstorming that preceded ISOE establishment, and he became the first head of the ISOE European Technical Centre, in charge of the world database development and management from 1991 to 2007. For writing this report, he made use of his own souvenirs and documentation as well as of those of tens of ISOE participants, both from major international and regional organisations (OECD/NEA, IAEA, EC and BNL), nuclear power plant utilities and national regulatory authorities. He voluntarily focused not only on the technical aspects but also on the human components of that story. This was done through personal interviews with many individuals who have played an important role at one moment of ISOE life, the analysis of answers to a questionnaire, and reviews of the minutes of many ISOE meetings that were held before and after the official establishment of the ISOE, along its lifespan to date. The most important inputs were the accounts from many individuals having very actively participated in the ISOE life at one step or another. The contacts were not always easy to make 15 or 20 years later. But in general, the questions were welcomed and the answers to the interviews and to a short questionnaire have fed this report. More than 50 individuals have answered these requests one way or another. Some have followed ISOE birth and premises; some have not seen the first steps of ISOE but have participated later on or are still participating. Some have been able to provide pictures, drawings or relevant publications. All their accounts are part of the collective memory of that important adventure shared during the last two decades by many individuals all over the world. They have allowed a more lively description than the one that would have come solely from documents, which have also been checked. This report provides excerpts of their interviews verbatim and written answers. This report is divided into three parts: Chapter 2: Why ISOE? Chapter 3: What has been the evolution of ISOE? Chapter 4: How has ISOE been perceived and is now perceived?

  19. Denver Reengineers: By Relying More on Vendors and Technology, Jo Sarling Explains How the Denver Public Library Shifted Resources to the Public

    Science.gov (United States)

    Sarling, Jo

    2005-01-01

    This article gives details of the developments and changes in the Denver Public Library (DPL). Through a review of advancements in technology, vendor capabilities, staffing levels and talent, as well as outsourcing opportunities, DPL reinvented its workflow and processing. The result? The once giant stacks of books, CDs, videos, and DVDs waiting…

  20. Measuring mental workload with the NASA-TLX needs to examine each dimension rather than relying on the global score: an example with driving.

    Science.gov (United States)

    Galy, Edith; Paxion, Julie; Berthelon, Catherine

    2018-04-01

    The distinction between several components of mental workload is often made in the ergonomics literature. However, measurements used are often established from a global score, notably with several questionnaires that originally reflect several dimensions. The present study tested the effect of driving situation complexity, experience and subjective levels of tension and alertness on each dimension of the NASA-TLX questionnaire of workload, in order to highlight the potential influence of intrinsic, extraneous and germane load factors. The results showed that, in complex situation, mental, temporal and physical demand (load dimensions) increased, and that novice drivers presented high physical demand when subjective tension was low on performance. Moreover, increase of mental and physical demand increased effort. It thus, appears essential to distinguish the different components of mental workload used in the NASA-TLX questionnaire. Practitioner Summary: Currently, global score of NASA-TLX questionnaire is used to measure mental workload. Here, we considered independently each dimension of NASA-TLX, and results showed that mental load factors (driving situation complexity, experience, subjective tension and alertness) had a different effect on dimensions, questioning global score use to evaluate workload.

  1. Chemotropism and Cell Fusion in Neurospora crassa Relies on the Formation of Distinct Protein Complexes by HAM-5 and a Novel Protein HAM-14.

    Science.gov (United States)

    Jonkers, Wilfried; Fischer, Monika S; Do, Hung P; Starr, Trevor L; Glass, N Louise

    2016-05-01

    In filamentous fungi, communication is essential for the formation of an interconnected, multinucleate, syncytial network, which is constructed via hyphal fusion or fusion of germinated asexual spores (germlings). Anastomosis in filamentous fungi is comparable to other somatic cell fusion events resulting in syncytia, including myoblast fusion during muscle differentiation, macrophage fusion, and fusion of trophoblasts during placental development. In Neurospora crassa, fusion of genetically identical germlings is a highly dynamic and regulated process that requires components of a MAP kinase signal transduction pathway. The kinase pathway components (NRC-1, MEK-2 and MAK-2) and the scaffold protein HAM-5 are recruited to hyphae and germling tips undergoing chemotropic interactions. The MAK-2/HAM-5 protein complex shows dynamic oscillation to hyphae/germling tips during chemotropic interactions, and which is out-of-phase to the dynamic localization of SOFT, which is a scaffold protein for components of the cell wall integrity MAP kinase pathway. In this study, we functionally characterize HAM-5 by generating ham-5 truncation constructs and show that the N-terminal half of HAM-5 was essential for function. This region is required for MAK-2 and MEK-2 interaction and for correct cellular localization of HAM-5 to "fusion puncta." The localization of HAM-5 to puncta was not perturbed in 21 different fusion mutants, nor did these puncta colocalize with components of the secretory pathway. We also identified HAM-14 as a novel member of the HAM-5/MAK-2 pathway by mining MAK-2 phosphoproteomics data. HAM-14 was essential for germling fusion, but not for hyphal fusion. Colocalization and coimmunoprecipitation data indicate that HAM-14 interacts with MAK-2 and MEK-2 and may be involved in recruiting MAK-2 (and MEK-2) to complexes containing HAM-5. Copyright © 2016 by the Genetics Society of America.

  2. Can we rely on simulated patients' satisfaction with their consultation for assessing medical students' communication skills? A cross-sectional study.

    Science.gov (United States)

    Gude, T; Grimstad, H; Holen, A; Anvik, T; Baerheim, A; Fasmer, O B; Hjortdahl, P; Vaglum, P

    2015-12-18

    In medical education, teaching methods offering intensive practice without high utilization of faculty resources are needed. We investigated whether simulated patients' (SPs') satisfaction with a consultation could predict professional observers' assessment of young doctors' communication skills. This was a comparative cross-sectional study of 62 videotaped consultations in a general practice setting with young doctors who were finishing their internship. The SPs played a female patient who had observed blood when using the toilet, which had prompted a fear of cancer. Immediately afterwards, the SP rated her level of satisfaction with the consultation, and the scores were dichotomized into satisfaction or dissatisfaction. Professional observers viewed the videotapes and assessed the doctors' communication skills using the Arizona Communication Interview Rating Scale (ACIR). Their ratings of communication skills were dichotomized into acceptable versus unacceptable levels of competence. The SPs' satisfaction showed a predictive power of 0.74 for the observers' assessment of the young doctors and whether they reached an acceptable level of communication skills. The SPs' dissatisfaction had a predictive power of 0.71 for the observers' assessment of an unacceptable communication level. The two assessment methods differed in 26% of the consultations. When SPs felt relief about their cancer concern after the consultation, they assessed the doctors' skills as satisfactory independent of the observers' assessment. Accordance between the dichotomized SPs' satisfaction score and communication skills assessed by observers (using the ACIR) was in the acceptable range. These findings suggest that SPs' satisfaction scores may provide a reliable source for assessing communication skills in educational programs for medical trainees (students and young doctors). Awareness of the patient's concerns seems to be of vital importance to patient satisfaction.

  3. Further evidence that rats rely on local rather than global spatial information to locate a hidden goal: reply to Cheng and Gallistel (2005).

    Science.gov (United States)

    McGregor, Anthony; Jones, Peter M; Good, Mark A; Pearce, John M

    2006-07-01

    Naive male Hooded Lister rats (Rattus norvegicus) were required to find a submerged platform in a right-angled corner between a long and a short wall of a pool in the shape of an irregular pentagon. Tests in a rectangular pool revealed a preference for the corners that corresponded with the correct corner in the pentagon. These findings indicate that rats identified the correct corner in the pentagon by local cues. They contradict the suggestion that rats navigate by moving in a particular direction relative to the principal axis of the shape of their environment.

  4. Wait at your own risk. Relying on a vendor to manage ICD-10 conversion can mean being held accountable for lost revenue.

    Science.gov (United States)

    Lawrence, Daphne

    2009-12-01

    CIOs must have an ICD-10 conversion strategy in place now, since many systems will be impacted. Creating a timeline can help determine whether an organization is in good shape. CIOs who have not yet implemented an EMR should consider using SNOMED. As ICD-10 approaches, it will be necessary to monitor AR days daily, instead of monthly. Organizations need to designate and empower an ICD-10 leader and begin staff training efforts early.

  5. The Two Rivers of Public Education: Why Our Representative Democracy Relies on Both Individualism and Community to Be Delivered through Its Public Schools

    Science.gov (United States)

    Draayer, Donald

    2011-01-01

    America is blessed with two river systems that feed and nourish the country by their periodic flooding. One mighty river is "individualism" (the entrepreneurial drive to advance and make a difference). The other river is "community" (wherein communal interests strengthen the whole community over the parts). Monitoring and regulating these two…

  6. Moralized Rationality: Relying on Logic and Evidence in the Formation and Evaluation of Belief Can Be Seen as a Moral Issue

    OpenAIRE

    St?hl, Tomas; Zaal, Maarten P.; Skitka, Linda J.

    2016-01-01

    In the present article we demonstrate stable individual differences in the extent to which a reliance on logic and evidence in the formation and evaluation of beliefs is perceived as a moral virtue, and a reliance on less rational processes is perceived as a vice. We refer to this individual difference variable as moralized rationality. Eight studies are reported in which an instrument to measure individual differences in moralized rationality is validated. Results show that the Moralized Rat...

  7. Do clinicians decide relying primarily on Bayesians principles or on Gestalt perception? Some pearls and pitfalls of Gestalt perception in medicine.

    Science.gov (United States)

    Cervellin, Gianfranco; Borghi, Loris; Lippi, Giuseppe

    2014-08-01

    Clinical judgment is a foundation of medical practice and lies at the heart of a physician's knowledge, expertise and skill. Although clinical judgment is an active part of all medical fields, thus including diagnosis and therapy, communication and decision making, it is still poorly defined. It can be considered a synthesis of intuition (mainly based on Gestalt principles) and an analytical approach. Gestalt perception finds its rationale in the evidence that perception of any given object or experience exhibits intrinsic qualities that cannot be completely reduced to visual, auditory, tactile, olfactory, or gustatory components. Thus, perceptions are not constructed in a "bottom-up" fashion from such elements, but are instead globally perceived, in a more "top-down" fashion. Gestalt perception, if cautiously and carefully combined with structured (techno)logical tools, would permit one to defoliate the often too-many-branches built diagnostic trees, and help physicians to better develop their competency. On the other hand, the practice of evidence-based medicine lies in the integration of individual clinical expertise and judgment with the best available external clinical evidence from systematic research. This article is aimed at providing some general concepts about Gestalt perception, and to discuss some aspects of clinical practice potentially influenced by this approach.

  8. Chip-interleaved optical code division multiple access relying on a photon-counting iterative successive interference canceller for free-space optical channels.

    Science.gov (United States)

    Zhou, Xiaolin; Zheng, Xiaowei; Zhang, Rong; Hanzo, Lajos

    2013-07-01

    In this paper, we design a novel Poisson photon-counting based iterative successive interference cancellation (SIC) scheme for transmission over free-space optical (FSO) channels in the presence of both multiple access interference (MAI) as well as Gamma-Gamma atmospheric turbulence fading, shot-noise and background light. Our simulation results demonstrate that the proposed scheme exhibits a strong MAI suppression capability. Importantly, an order of magnitude of BER improvements may be achieved compared to the conventional chip-level optical code-division multiple-access (OCDMA) photon-counting detector.

  9. Relying on the National Mobile Disaster Hospital as a business continuity strategy in the aftermath of a tornado: The Louisville experience.

    Science.gov (United States)

    Kearns, Randy D; Stringer, Lew; Craig, James; Godette-Crawford, Regina; Black, Paul S; Andra, David L; Winslow, James

    2017-01-01

    On 28th April, 2014, a tornado left much of Louisville, MS and the local hospital, Winston Medical Center, in ruin. In the USA, temporary hospital solutions have been used to augment the mainstream healthcare system since the American Civil War. As memories fade, however, the necessary readiness for a temporary hospital also fades, at times leaving a patchwork of resources either underfunded or abandoned. With the creation of the Hospital Preparedness Program, several temporary hospital solutions were created in various states across the USA. In the present case, Mississippi and North Carolina resources were used in Louisville in the aftermath of a direct impact that destroyed the hospital and nursing home. In the hours that followed, after lives were saved and patients safely relocated, a frank assessment confirmed the structural loss of the hospital. Local emergency responders, hospital staff, state and federal representatives all rallied with the aim of saving the community's only hospital. The steps taken in Louisville and the deliberate restoration of these essential services offer a learning opportunity for all involved in healthcare disaster preparedness, response and recovery.

  10. 2D and 3D modeling of wave propagation in cold magnetized plasma near the Tore Supra ICRH antenna relying on the perfecly matched layer technique

    International Nuclear Information System (INIS)

    Jacquot, J; Colas, L; Clairet, F; Goniche, M; Hillairet, J; Lombard, G; Heuraux, S; Milanesio, D

    2013-01-01

    A novel method to simulate ion cyclotron wave coupling in the edge of a tokamak plasma with the finite element technique is presented. It is applied in the commercial software COMSOL Multiphysics. Its main features include the perfectly matched layer (PML) technique to emulate radiating boundary conditions beyond a critical cutoff layer for the fast wave (FW), full-wave propagation across the inhomogeneous cold peripheral plasma and a detailed description of the wave launcher geometry. The PML technique, while widely used in numerical simulations of wave propagation, has scarcely been used for magnetized plasmas, due to specificities of this gyrotropic material. A versatile PML formulation, valid for full dielectric tensors, is summarized and interpreted as wave propagation in an artificial medium. The behavior of this technique has been checked for plane waves on homogeneous plasmas. Wave reflection has been quantified and compared to analytical predictions. An incompatibility issue for adapting the PML for forward (FW) and backward (slow wave (SW)) propagating waves simultaneously has been evidenced. In a tokamak plasma, this critical issue is overcome by taking advantage of the inhomogeneous density profile to reflect the SW before it reaches the PML. The simulated coupling properties of a Tore Supra ion cyclotron resonance heating (ICRH) antenna have been compared to experimental values in a situation of good single-pass absorption. The necessary antenna elements to include in the geometry to recover the coupling properties obtained experimentally are also discussed. (paper)

  11. Apoptotic DNA Degradation into Oligonucleosomal Fragments, but Not Apoptotic Nuclear Morphology, Relies on a Cytosolic Pool of DFF40/CAD Endonuclease*

    Science.gov (United States)

    Iglesias-Guimarais, Victoria; Gil-Guiñon, Estel; Gabernet, Gisela; García-Belinchón, Mercè; Sánchez-Osuna, María; Casanelles, Elisenda; Comella, Joan X.; Yuste, Victor J.

    2012-01-01

    Apoptotic cell death is characterized by nuclear fragmentation and oligonucleosomal DNA degradation, mediated by the caspase-dependent specific activation of DFF40/CAD endonuclease. Here, we describe how, upon apoptotic stimuli, SK-N-AS human neuroblastoma-derived cells show apoptotic nuclear morphology without displaying concomitant internucleosomal DNA fragmentation. Cytotoxicity afforded after staurosporine treatment is comparable with that obtained in SH-SY5Y cells, which exhibit a complete apoptotic phenotype. SK-N-AS cell death is a caspase-dependent process that can be impaired by the pan-caspase inhibitor q-VD-OPh. The endogenous inhibitor of DFF40/CAD, ICAD, is correctly processed, and dff40/cad cDNA sequence does not reveal mutations altering its amino acid composition. Biochemical approaches show that both SH-SY5Y and SK-N-AS resting cells express comparable levels of DFF40/CAD. However, the endonuclease is poorly expressed in the cytosolic fraction of healthy SK-N-AS cells. Despite this differential subcellular distribution of DFF40/CAD, we find no differences in the subcellular localization of both pro-caspase-3 and ICAD between the analyzed cell lines. After staurosporine treatment, the preferential processing of ICAD in the cytosolic fraction allows the translocation of DFF40/CAD from this fraction to a chromatin-enriched one. Therefore, the low levels of cytosolic DFF40/CAD detected in SK-N-AS cells determine the absence of DNA laddering after staurosporine treatment. In these cells DFF40/CAD cytosolic levels can be restored by the overexpression of their own endonuclease, which is sufficient to make them proficient at degrading their chromatin into oligonucleosome-size fragments after staurosporine treatment. Altogether, the cytosolic levels of DFF40/CAD are determinants in achieving a complete apoptotic phenotype, including oligonucleosomal DNA degradation. PMID:22253444

  12. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  13. High- and Low-Order Overtaking-Ability Affordances: Drivers Rely on the Maximum Velocity and Acceleration of Their Cars to Perform Overtaking Maneuvers.

    Science.gov (United States)

    Basilio, Numa; Morice, Antoine H P; Marti, Geoffrey; Montagne, Gilles

    2015-08-01

    The aim of this study was to answer the question, Do drivers take into account the action boundaries of their car when overtaking? The Morice et al. affordance-based approach to visually guided overtaking suggests that the "overtake-ability" affordance can be formalized as the ratio of the "minimum satisfying velocity" (MSV) of the maneuver to the maximum velocity (V(max)) of the driven car. In this definition, however, the maximum acceleration (A(max)) of the vehicle is ignored. We hypothesize that drivers may be sensitive to an affordance redefined with the ratio of the "minimum satisfying acceleration" (MSA) to the A(max) of the car. Two groups of nine drivers drove cars differing in their A(max). They were instructed to attempt overtaking maneuvers in 25 situations resulting from the combination of five MSA and five MSV values. When overtaking frequency was expressed as a function of MSV and MSA, maneuvers were found to be initiated differently for the two groups. However, when expressed as a function of MSV/V(max) and MSA/A(max), overtaking frequency was quite similar for both groups. Finally, a multiple regression coefficient analysis demonstrated that overtaking decisions are fully explained by a composite variable comprising MSA/A(max) and the time required to reach MSV. Drivers reliably decide whether overtaking is safe (or not) by using low- and high-order variables taking into account their car's maximum velocity and acceleration, respectively, as predicted by "affordance-based control" theory. Potential applications include the design of overtaking assistance, which should exploit the MSA/A(max) variables in order to suggest perceptually relevant overtaking solutions. © 2015, Human Factors and Ergonomics Society.

  14. High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor

    International Nuclear Information System (INIS)

    Auf, Gregor; Vajkoczy, Peter; Seno, Masaharu; Bikfalvi, Andreas; Minchenko, Dmitri; Minchenko, Oleksandr; Moenner, Michel; Jabouille, Arnaud; Delugin, Maylis; Guérit, Sylvaine; Pineau, Raphael; North, Sophie; Platonova, Natalia; Maitre, Marlène; Favereaux, Alexandre

    2013-01-01

    Epidermal growth factor (EGF) receptors contribute to the development of malignant glioma. Here we considered the possible implication of the EGFR ligand epiregulin (EREG) in glioma development in relation to the activity of the unfolded protein response (UPR) sensor IRE1α. We also examined EREG status in several glioblastoma cell lines and in malignant glioma. Expression and biological properties of EREG were analyzed in human glioma cells in vitro and in human tumor xenografts with regard to the presence of ErbB proteins and to the blockade of IRE1α. Inactivation of IRE1α was achieved by using either the dominant-negative strategy or siRNA-mediated knockdown. EREG was secreted in high amounts by U87 cells, which also expressed its cognate EGF receptor (ErbB1). A stimulatory autocrine loop mediated by EREG was evidenced by the decrease in cell proliferation using specific blocking antibodies directed against either ErbB1 (cetuximab) or EREG itself. In comparison, anti-ErbB2 antibodies (trastuzumab) had no significant effect. Inhibition of IRE1α dramatically reduced EREG expression both in cell culture and in human xenograft tumor models. The high-expression rate of EREG in U87 cells was therefore linked to IRE1α, although being modestly affected by chemical inducers of the endoplasmic reticulum stress. In addition, IRE1-mediated production of EREG did not depend on IRE1 RNase domain, as neither the selective dominant-negative invalidation of the RNase activity (IRE1 kinase active) nor the siRNA-mediated knockdown of XBP1 had significant effect on EREG expression. Finally, chemical inhibition of c-Jun N-terminal kinases (JNK) using the SP600125 compound reduced the ability of cells to express EREG, demonstrating a link between the growth factor production and JNK activation under the dependence of IRE1α. EREG may contribute to glioma progression under the control of IRE1α, as exemplified here by the autocrine proliferation loop mediated in U87 cells by the growth factor through ErbB1

  15. Visualizadores de imagens médicas gratuitos: é possível trabalhar apenas com eles? Freeware medical image viewers: can we rely only on them?

    Directory of Open Access Journals (Sweden)

    Filipe Ramos Barra

    2010-10-01

    Full Text Available OBJETIVO: Pesquisar visualizadores de imagens médicas gratuitos disponíveis na internet capazes de funcionar como cliente PACS (picture archiving and communication system e avaliar suas principais funções e a viabilidade do uso em computadores pessoais. MATERIAIS E MÉTODOS: Foi feita pesquisa, no Google e em sites especializados, por programas gratuitos disponíveis para o Windows. Foram encontrados cerca de 70, sendo 11 capazes de funcionar como cliente PACS, e selecionados seis destes para análise: ClearCanvas Workstation, KPACS, Onis, Synedra View Personal, Mito e Tudor DicomViewer. Com base nas necessidades dos autores, 16 funções foram avaliadas. RESULTADOS: Dos seis programas avaliados, dois possuem 10 das 16 funções avaliadas e um possui apenas duas. Três realizam MPR (reconstrução multiplanar, um realiza MIP (reconstrução por projeção de intensidade máxima, dois realizam VR (renderizações volumétricas, dois funcionam como servidor PACS, dois geram CDs, um realiza fusão de imagens, três permitem utilizar múltiplos monitores e apenas um não é compatível com Windows 7. CONCLUSÃO: Diversos programas gratuitos estão disponíveis e não existe nenhum completo. Cabe ao usuário analisar e selecionar o programa que melhor se enquadra nas suas necessidades, porém, os programas Onis, Synedra e ClearCanvas se destacam, cada um com suas peculiaridades. É totalmente viável o uso de programas gratuitos para o dia-a-dia do radiologista.OBJECTIVE: To search in the internet for freeware medical image viewers capable of running as a PACS (picture archiving and communication system client, and to evaluate their main functions as well as the feasibility of their use in personal computers. MATERIALS AND METHODS: The Google search engine and specialized sites were utilized in the search for freeware softwares for Windows. The authors have found about 70 and among them 11 were able to run as PACS clients. Six were selected for analysis: ClearCanvas Workstation, KPACS, Onis, Synedra View Personal, Mito and Tudor DicomViewer. Sixteen functions selected according to the authors' needs were evaluated. RESULTS: Among the six applications, two presented 10 of the 16 functions, and one of them presented only two. Three perform MPR (multiplanar reconstruction, one performs MIP (maximum intensity projection, two perform VR (volume rendering, two can run as a PACS server, two can create CDs, one performs images fusion, three allow the use of multiple monitors and only one is not compatible with Windows 7. CONCLUSION: Although several freeware applications are available, no one of them is complete. It is up to the users to analyze and select the software that best suits their needs. However, Onis, Synedra and ClearCanvas stand out because of their own peculiarities. The use of freeware image viewers is entirely feasible in the radiologists' daily routine.

  16. The Bone Marrow-Mediated Protection of Myeloproliferative Neoplastic Cells to Vorinostat and Ruxolitinib Relies on the Activation of JNK and PI3K Signalling Pathways.

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    Bruno A Cardoso

    Full Text Available The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi, albeit with poorer tolerance. Here, we show that bone marrow (BM stromal cells (HS-5 protected MPN-derived cell lines (SET-2; HEL and UKE-1 and MPN patient-derived BM cells from the cytotoxic effects of Ruxolitinib and the HDACi Vorinostat. This protective effect was mediated, at least in part, by the secretion of soluble factors from the BM stroma. In addition, it correlated with the activation of signalling pathways important for cellular homeostasis, such as JAK-STAT, PI3K, JNK, MEK-ERK and NF-κB. Importantly, the pharmacological inhibition of JNK and PI3K pathways completely abrogated the BM protective effect on MPN cell lines and MPN patient samples. Our findings shed light on mechanisms of tumour survival and may indicate novel therapeutic approaches for the treatment of MPN.

  17. The Bone Marrow-Mediated Protection of Myeloproliferative Neoplastic Cells to Vorinostat and Ruxolitinib Relies on the Activation of JNK and PI3K Signalling Pathways

    Science.gov (United States)

    Cardoso, Bruno A.; Belo, Hélio; Barata, João T.; Almeida, António M.

    2015-01-01

    The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN) are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi), albeit with poorer tolerance. Here, we show that bone marrow (BM) stromal cells (HS-5) protected MPN-derived cell lines (SET-2; HEL and UKE-1) and MPN patient-derived BM cells from the cytotoxic effects of Ruxolitinib and the HDACi Vorinostat. This protective effect was mediated, at least in part, by the secretion of soluble factors from the BM stroma. In addition, it correlated with the activation of signalling pathways important for cellular homeostasis, such as JAK-STAT, PI3K, JNK, MEK-ERK and NF-κB. Importantly, the pharmacological inhibition of JNK and PI3K pathways completely abrogated the BM protective effect on MPN cell lines and MPN patient samples. Our findings shed light on mechanisms of tumour survival and may indicate novel therapeutic approaches for the treatment of MPN. PMID:26623653

  18. temprana. Un enfoque analítico en un estudio piloto

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    Gloria Garavito

    2013-01-01

    Full Text Available Objetivos: Identificar biomarcadores de susceptibilidad para AIJ poliarticular y AR de instalación temprana por estudio del polimorfismos de MHC/HLA-DRB1* y PTPN22. Materiales y métodos: Se realizó un estudio de casos y controles con una relación 1:2. Todos los sujetos de investigación y los controles provinieron de una corta anidada perteneciente a un proyecto institucional; 30 pacientes con AIJ y 30 con AR de instalación temprana. Como controles se estudiaron 60 individuos sanos. El ADN se obtuvo por salt- ing out modificado. La tipificación de los alelos MHC/DRB1* se realizó por PCR-SSP y en el polimorfismo (C1858T del sistema PTPN22 se utilizó PCR-RTq. Resultados: Para AIJ Poliarticular, el alelo DRB1*0404 se asoció con susceptibilidad (OR=10.82; p<0.05, en el grupo con AR de instalación temprana, DRB1*0101 se mostró como marcador de susceptibilidad (OR=4.04; p<0.05. Se destaca que el alelo HLA- DRB1*0701 aparece como marcador protector para ambas patologías (OR=0,15; p<0,05. El polimorfismo del SNP (C1858T PTPN22 no se asoció con AIJ Poliarticular. En con- traste, en AR de instalación temprana, el Alelo CC se asoció con protección p<0.05. En el mismo grupo, CT/TT se mostró como un marcador de susceptibilidad <0.05. El análisis de la secuencia aminoacídica 70QRRAA74 del epítope compartido se asoció con susceptibili- dad para ambas entidades (p<0.05 y la secuencia 70DRRGQ74 con protección en ambos grupos de pacientes (p<0.05. Conclusión: Se destaca que en la asociación con la secuencia del epítope compartido, la ubicación del tipo de aminoácido y posición del mismo define probable asociación como marcador molecular de susceptibilidad en ambas entidades. Los polimorfismos comparti- dos sugieren un origen genético común para ambas entidades.

  19. Role of a Novel Human Leukocyte Antigen-DQA1*01:02;DRB1*15:01 Mixed Isotype Heterodimer in the Pathogenesis of “Humanized” Multiple Sclerosis-like Disease*

    Science.gov (United States)

    Kaushansky, Nathali; Eisenstein, Miriam; Boura-Halfon, Sigalit; Hansen, Bjarke Endel; Nielsen, Claus Henrik; Milo, Ron; Zeilig, Gabriel; Lassmann, Hans; Altmann, Daniel M.; Ben-Nun, Avraham

    2015-01-01

    Gene-wide association and candidate gene studies indicate that the greatest effect on multiple sclerosis (MS) risk is driven by the HLA-DRB1*15:01 allele within the HLA-DR15 haplotype (HLA-DRB1*15:01-DQA1*01:02-DQB1*0602-DRB5*01:01). Nevertheless, linkage disequilibrium makes it difficult to define, without functional studies, whether the functionally relevant effect derives from DRB1*15:01 only, from its neighboring DQA1*01:02-DQB1*06:02 or DRB5*01:01 genes of HLA-DR15 haplotype, or from their combinations or epistatic interactions. Here, we analyzed the impact of the different HLA-DR15 haplotype alleles on disease susceptibility in a new “humanized” model of MS induced in HLA-transgenic (Tg) mice by human oligodendrocyte-specific protein (OSP)/claudin-11 (hOSP), one of the bona fide potential primary target antigens in MS. We show that the hOSP-associated MS-like disease is dominated by the DRB1*15:01 allele not only as the DRA1*01:01;DRB1*15:01 isotypic heterodimer but also, unexpectedly, as a functional DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. The contribution of HLA-DQA1/DRB1 mixed isotype heterodimer to OSP pathogenesis was revealed in (DRB1*1501xDQB1*0602)F1 double-Tg mice immunized with hOSP(142–161) peptide, where the encephalitogenic potential of prevalent DRB1*1501/hOSP(142–161)-reactive Th1/Th17 cells is hindered due to a single amino acid difference in the OSP(142–161) region between humans and mice; this impedes binding of DRB1*1501 to the mouse OSP(142–161) epitope in the mouse CNS while exposing functional binding of mouse OSP(142–161) to DQA1*01:02;DRB1*15:01 mixed isotype heterodimer. This study, which shows for the first time a functional HLA-DQA1/DRB1 mixed isotype heterodimer and its potential association with disease susceptibility, provides a rationale for a potential effect on MS risk from DQA1*01:02 through functional DQA1*01:02;DRB1*15:01 antigen presentation. Furthermore, it highlights a potential contribution to MS

  20. Haplotype Analysis Discriminates Genetic Risk for DR3-Associated Endocrine Autoimmunity and Helps Define Extreme Risk for Addison’s Disease

    Science.gov (United States)

    Baker, Peter R.; Baschal, Erin E.; Fain, Pam R.; Triolo, Taylor M.; Nanduri, Priyaanka; Siebert, Janet C.; Armstrong, Taylor K.; Babu, Sunanda R.; Rewers, Marian J.; Gottlieb, Peter A.; Barker, Jennifer M.; Eisenbarth, George S.

    2010-01-01

    Context: Multiple autoimmune disorders (e.g. Addison’s disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. Objective: The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison’s disease (AD). Design, Setting, and Participants: Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34. Main Outcome Measures: AD and genotype were measured. Result: Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10−4) and 13% of general population controls (P = 3.00 × 10−19). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10−191). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10−5) and type 1 diabetes patients (73%, P = 1.93 × 10−3). Analysis of 1228 SNPs across the MHC for individuals with AD revealed a shorter conserved haplotype (3.8) with the loss of the extended conserved 3.8.1 haplotype approximately halfway between HLA-B and HLA-A. Conclusion: Extreme risk for AD, especially in multiplex families, is associated with haplotypic DR3 variants, in particular a portion (3.8) but not all of the conserved 3.8.1 haplotype. PMID:20631027

  1. Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome.

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    Shu-Jun Ding

    2016-10-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV in East Asian countries. The role of human leukocyte antigen (HLA in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.A total of 84 confirmed SFTS patients (patient group and 501 unrelated non-SFTS patients (healthy individuals as control group from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR and 95% confidence intervals (CI were calculated by Woolf's method.A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252. The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96 without significance(Pc>0.05. A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07.The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

  2. Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

    Science.gov (United States)

    Santos, Ana M; Peña, Paola; Avila, Mabel; Briceño, Ignacio; Jaramillo, Carlos; Vargas-Alarcon, Gilberto; Rueda, Juan C; Saldarriaga, Eugenia-Lucia; Angarita, Jose-Ignacio; Martinez-Rodriguez, Nancy; Londono, John

    2017-04-01

    There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

  3. HLA variants rs9271366 and rs9275328 are associated with systemic lupus erythematosus susceptibility in Malays and Chinese.

    Science.gov (United States)

    Chai, H C; Phipps, M E; Othman, I; Tan, L P; Chua, K H

    2013-02-01

    Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort. SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated. The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p < 0.05). As for HLA-DQB1/HLA-DQA2 rs9275328, the minor allele T and the heterozygous genotype CT conferred protective effect to SLE in Malaysians, as well as in Malays and Chinese, by having OR < 1 and p value <0.05. Both SNPs did not show associations to SLE in Indians. D' and r (2) values for the two SNPs in LD analysis were 0.941 and 0.065, respectively, with haplotype GC and AT being significantly associated with SLE (p < 5.0 × 10(-4)) after 10,000 permutations were performed. The MDR test clustered the genotype combinations of GG and CC, and AG and CC of rs9271366 and rs9275328, accordingly, as high-risk group, and the two SNPs interacted redundantly by removing 1.96% of the entropy. Our findings suggest that in addition to some classical HLA variants, rs9271366 and rs9275328 are additional polymorphisms worth considering in the Malaysian and possibly in

  4. A Combination of CD28 (rs1980422 and IRF5 (rs10488631 Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study.

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    Lucia Vernerova

    Full Text Available The aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA and redundancy analysis (RDA.A total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601, STAT4 G/T (rs7574865, CTLA4 A/G (rs3087243, TRAF1/C5 A/G (rs3761847, IRF5 T/C (rs10488631, TNFAIP3 C/T (rs5029937, AFF3 A/T (rs11676922, PADI4 C/T (rs2240340, CD28 T/C (rs1980422, CSK G/A (rs34933034 and FCGR3A A/C (rs396991, rheumatoid factor (RF, anti-citrullinated protein antibodies (ACPA and clinical status was analysed using the LDA and RDA.HLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002. The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001. The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.The association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.

  5. HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

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    Gragert, Loren; Eapen, Mary; Williams, Eric; Freeman, John; Spellman, Stephen; Baitty, Robert; Hartzman, Robert; Rizzo, J. Douglas; Horowitz, Mary; Confer, Dennis; Maiers, Martin

    2018-01-01

    Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in

  6. The value of some genetic factors for prediction of chronic hepatitis C antiviral treatment effectiveness

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    V. M. Mitsura

    2014-01-01

    Full Text Available Aim: To determine the value of gene polymorphisms of interleukin-28B (IL28B, RNase L, HLA DRB1*1101 and HLADQB1*03 alleles as predictors of antiviral treatment efficacy in patients with chronic hepatitis C (CHC.Material and methods. A total of 156 in-patients with chronic hepatitis C (65.4% men, 62.4% had genotype 1 hepatitis C virus – HCV were studied. The results of treatment with interferon (IFN and ribavirin (RBV were analyzed in 74 patients. Polymerase chain reaction identified single nucleotide polymorphisms (SNP of the gene IL28B 39743165T>G (rs8099917, SNP 39738787C> T (rs12979860, RNase L gene (1385G>A, HLA DRB1*1101 and HLA-DQB1*03 alleles.Results. In patients with HCV genotype 1 mutant alleles were more common in SNP 39743165T>G (p=0.001 and 39738787C>T (p=0.0002 than in patients with other genotypes. Response to therapy IFN/RBV was higher in those with “favorable” TT variant (SNP 39743165T>G and CC (SNP 39738787C>T, in those with their combination virologic response ffect were found according to genes IL28B and RNase L SNP variants, DRB1*1101 and HLA-DQB1*03 alleles.Conclusion. Testing for SNP 39738787C>T of IL28B gene is recommended before starting therapy IFN / RBV for all patients with genotype 1 HCV as a predictor of treatment response. Testing SNP 1385G>A gene RNase L and DRB1*1101, HLA-DQB1*03 alleles has no apparent prognostic value for patients with CHC antiviral therapy.

  7. Congruence as a measurement of extended haplotype structure across the genome

    Science.gov (United States)

    2012-01-01

    Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies. PMID:22369243

  8. In silico analysis of candidate proteins sharing homology with Streptococcus agalactiae proteins and their role in male infertility.

    Science.gov (United States)

    Parida, Rajeshwari; Samanta, Luna

    2017-02-01

    Leukocytospermia is a physiologic condition defined as human semen with a leukocyte count of >1 x 10 6 cells/ml that is often correlated with male infertility. Moreover, bacteriospermia has been associated with leukocytospermia ultimately leading to male infertility. We have found that semen samples with >1 x 10 6 /ml leukocytes and/or bacteriospermia have oxidative predominance as evidenced by augmented protein carbonyl and lipid peroxidation status of the semen which is implicated in sperm dysfunction. It has been reported that Streptococcus agalactiae is present in bacteriospermic samples. Previous research has shown that human leukocyte antigen beta chain paralog (HLA-DRB) alleles interact best with the infected sperm cells rather than the non-infected cells. Little is known about the interaction of major histocompatibility complex (MHC) present on leukocytes with the sperm upon bacterial infection and how it induces an immunological response which we have addressed by epitope mapping. Therefore, we examined MHC class II derived bacterial peptides which might have human sperm-related functional aspects. Twenty-two S. agalactiae proteins were obtained from PUBMED protein database for our study. Protein sequences with more than two accession numbers were aligned using CLUSTAL Omega to check their conservation pattern. Each protein sequence was then analyzed for T-cell epitope prediction against HLA-DRB alleles using the immune epitope database (IEDB) analysis tool. Out of a plethora of peptides obtained from this analysis, peptides corresponding to proteins of interest such as DNA binding response regulator, hyaluronate lyase and laminin binding protein were screened against the human proteome using Blastp. Interestingly, we have found bacterial peptides sharing homology with human peptides deciphering some of the important sperm functions. Antibodies raised against these probable bacterial antigens of fertility will not only help us understand the mechanism of

  9. A Combination of CD28 (rs1980422) and IRF5 (rs10488631) Polymorphisms Is Associated with Seropositivity in Rheumatoid Arthritis: A Case Control Study.

    Science.gov (United States)

    Vernerova, Lucia; Spoutil, Frantisek; Vlcek, Miroslav; Krskova, Katarina; Penesova, Adela; Meskova, Milada; Marko, Andrea; Raslova, Katarina; Vohnout, Branislav; Rovensky, Jozef; Killinger, Zdenko; Jochmanova, Ivana; Lazurova, Ivica; Steiner, Guenter; Smolen, Josef; Imrich, Richard

    2016-01-01

    The aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA). A total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA. HLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA. The association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA.

  10. Testing with fragrance mix. Is the addition of sorbitan sesquioleate to the constituents useful?

    Science.gov (United States)

    Frosch, P J; Pilz, B; Burrows, D; Camarasa, J G; Lachapelle, J M; Lahti, A; Menné, T; Wilkinson, J D

    1995-05-01

    In a multicentre study, the value of adding sorbitan sesquioleate (SSO) to the constituents of the 8% fragrance mix (FM) was investigated. In 7 centres, 709 consecutive patients were tested with 2 types of FM from different sources, its 8 constituents with 1% SSO, its 8 constituents without SSO, and 20% SSO. 5 patients (0.71%) reacted to the emulsifier SSO itself, read as definitely allergic on day 3/4. 53 patients reacted to either one of the mixes with an allergic type of reaction. When tested with the constituents without SSO, 41.5% showed an allergic reaction versus 54.7% with SSO. If both types of reactions were considered (allergic and irritant) 38.3% of 73 patients showed a positive "breakdown" result without SSO, versus 54.8% with SSO. The differences were statistically significant. Reactivity to FM constituents was changed in a specific pattern by addition of SSO--irritant reactions increased, particularly for cinnamic alcohol, eugenol, geraniol, oak moss and hydroxycitronellal, whereas others showed only a slight change. Allergic reactions were also increased by SSO, but the rank order of the top 3 sensitizers (isoeugenol, oak moss and eugenol) did not change. Cinnamic alcohol was the only constituent with decreased reactivity after addition of SSO. A positive history of fragrance sensitivity (HFS) was clearly associated with a positive allergic reaction to either the mix or 1 of its constituents (51% versus 28.6% with a negative HFS). Irritant reactions were linked to a negative HFS in a high proportion (64.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Reactivity to sorbitan sesquioleate affects reactivity to fragrance mix I.

    Science.gov (United States)

    Geier, Johannes; Schnuch, Axel; Lessmann, Holger; Uter, Wolfgang

    2015-11-01

    Fragrance mix I (FM I) and its single constituents contain 5% and 1% sorbitan sesquioleate (SSO), respectively. SSO is a rare sensitizer and a potential irritant. To determine whether the outcome of the FM I breakdown test is affected by positive patch test reactivity to SSO. A retrospective analysis of data from the Information Network of Departments of Dermatology, 1998-2013, was performed. The full FM I breakdown test including SSO was tested in 2952 patients. Of these, 154 (5.2%) had a positive patch test reaction to SSO 20% pet. and 2709 (91.8%) had a negative patch test reaction. Positive reactions to one or more of the single fragrances contained in the mix were significantly more common (82.5% versus 57.3%) in SSO-positive patients, who also had more multiple reactions than FM I-positive patients with negative SSO reactions (61.5% versus 21.3% patients with reactions to two or more fragrances). Our results indicate that reactivity to SSO markedly affects the outcome of patch testing with FM I and its single constituents. SSO must be an obligatory part of the full FM I breakdown test, and should ideally be included in the baseline series. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Non Inherited Maternal HLA Antigens in Susceptibility to Familial Rheumatoid Arthritis

    Science.gov (United States)

    Guthrie, Katherine A.; Tishkevich, Natalia R.; Nelson, J. Lee

    2009-01-01

    Objectives Some rheumatoid arthritis (RA) patients lack RA-associated HLA alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results. Methods We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium. Results Among 620 patients with one or both parents HLA-genotyped, RA patients informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs. NIPA revealed no significant difference (27% vs. 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ≥45 years at onset the reverse was observed (31% vs. 16% compared to 10% vs. 60%, p=0.008). DR4 encoding NIMA vs. NIPA did not differ in men. The SE did not differ in men or women. Conclusions Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA. PMID:18684745

  13. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    /GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...... not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR...

  14. Is rheumatoid arthritis a consequence of natural selection for enhanced tuberculosis resistance?

    Science.gov (United States)

    Mobley, James L

    2004-01-01

    Although the bubonic plague or "Black Death" is notorious for the toll it took on the population of Europe in the middle ages, another epidemic, the "White Death" of tuberculosis is responsible for millions of deaths worldwide over the past 300 years. With one in four deaths due to tuberculosis in Western Europe and the United States in the 19th century, this disease undoubtedly acted as a powerful genetic selective force. The epidemiology of modern day rheumatoid arthritis (RA) is strikingly similar to the epidemiology of tuberculosis 100-200 years ago, suggesting the possibility that genetic factors that enhanced survival in tuberculosis epidemics are now influencing susceptibility to RA. Recent advances in the analysis of genetic polymorphisms associated with disease have identified several genes linked to RA susceptibility that encode proteins involved in the immune response to Mycobacterium tuberculosis infection, including TNF-alpha, NRAMP1, PARP-1, HLA-DRB1, and PADI4. These results suggest that rheumatoid arthritis, and possibly other autoimmune diseases, are modern day manifestations of the genetic selective pressure exerted by tuberculosis epidemics of the recent past.

  15. Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans

    Directory of Open Access Journals (Sweden)

    Soo Heon Kwak

    2015-12-01

    Full Text Available Fulminant type 1 diabetes (T1DM is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05–HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009. A histidine residue at HLA-DRβ1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054. Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

  16. The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies.

    Science.gov (United States)

    McKay, Fiona C; Gatt, Prudence N; Fewings, Nicole; Parnell, Grant P; Schibeci, Stephen D; Basuki, Monica A I; Powell, Joseph E; Goldinger, Anita; Fabis-Pedrini, Marzena J; Kermode, Allan G; Burke, Therese; Vucic, Steve; Stewart, Graeme J; Booth, David R

    2016-02-01

    Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. Influence of the HLA class II polymorphism in chronic Chagas' disease.

    Science.gov (United States)

    Fernandez-Mestre, M T; Layrisse, Z; Montagnani, S; Acquatella, H; Catalioti, F; Matos, M; Balbas, O; Makhatadze, N; Dominguez, E; Herrera, F; Madrigal, A

    1998-04-01

    Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.

  18. HLA polymorphism in a Guarani-Indian population from Paraguay and its usefulness for the Hispano-Indian admixture study in Paraguay.

    Science.gov (United States)

    Benitez, O; Busson, M; Charron, D; Loiseau, P

    2011-02-01

    In this study we investigated the human leucocyte antigen-A (HLA-A), -B and DRB1 polymorphism of Native American population of Paraguay, the Guarani Indians. We found that the HLA variability consisted of 5 HLA-A, 7 HLA-B and 6 HLA-DRB1 groups of alleles and of several specific alleles (B*1504, B*3505, B*3912, B*4004, B*5104, DRB1*0411, DRB1*1413) common in other Native American populations. The comparison of the HLA polymorphism of the Guaranis from Paraguay with the «Mestizos» of Paraguay and the Spaniards showed that the «Mestizos» of Paraguay are genetically very distant from the Guarani Indians of Paraguay but much more close to the Spaniards. This can be explained, at least in part, by the history of the country. Our results are of importance in transplantation, in particular in the search for an unrelated donor for a Paraguayan patient requiring hematopoietic stem cell transplantation. © 2010 Blackwell Publishing Ltd.

  19. Does genetic diversity predict health in humans?

    Directory of Open Access Journals (Sweden)

    Hanne C Lie

    2009-07-01

    Full Text Available Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC, has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d(2 at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d(2 at nonMHC loci and at one MHC locus, linked to