Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes

DEFF Research Database (Denmark)

Wessman, Maija; Forsblom, Carol; Kaunisto, Mari A

2011-01-01

Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21-q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci...

Adolescent Susceptibility to Peer Influence in Sexual Situations.

Science.gov (United States)

Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

2016-03-01

One consistent predictor of adolescents' engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk taking. Participants were 300 early adolescents (Mage = 12.6 years; 53% female; 44% Caucasian) who completed (1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior and (2) a subsequent experimental procedure that simulated an Internet chat room in which youth believed that they were communicating with peers regarding these same hypothetical scenarios. In reality, these "peers" were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. In total, 78% of youth provided more risky responses in the chat room than those in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African-American boys. Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

[Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

Science.gov (United States)

Wang, Yi-Min; Guo, Wei; Zhang, Xiu-Feng; Li, Yan; Wang, Na; Ge, Hui; Wei, Li-Zhen; Wen, Deng-Gui; Zhang, Jian-Hui

2006-03-01

Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model. Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, Pnon-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89). SHMT1 1420C/T genotype could significantly reduce susceptibilities to ESCC and GCA among individuals from high risk areas in Hebei Province of China.

RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

Science.gov (United States)

Yang, Chun-Hua; Zhou, Tian-Biao

2015-12-01

Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 Chun-Hua Yang and Tian-Biao Zhou Relationship between the angiotensinogen A1166C gene polymorphism and the risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314566221, first published on February 1, 2015 doi: 10.1177/1470320314566221 Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 Articles published in an issue Guohui Liu, Tian-Biao Zhou, Zongpei Jiang, and Dongwen Zheng Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population Journal of Renin-Angiotensin-Aldosterone System March 2015 16: 165-171, first published on November 14, 2014 doi: 10.1177/1470320314557849 Weiqiang Zhong, Zhongliang Huang, Yong Wu, Zongpei Jiang, and Tian-Biao Zhou Association of aldosterone synthase (CYP11B2) gene polymorphism with IgA nephropathy risk and progression of IgA nephropathy Journal of Renin-Angiotensin-Aldosterone System September 2015 16: 660-665, first published on August 20, 2014 doi: 10.1177/1470320314524011.

The vitamin D receptor and T cell function

Directory of Open Access Journals (Sweden)

Martin eKongsbak

2013-06-01

Full Text Available The vitamin D receptor (VDR is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH2D3, regulates the expression of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH2D3-VDR signaling on immune function has been the focus of many recent studies as a link between 1,25(OH2D3 and sus-ceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. It is also becoming increasingly clear that microbes slow down immune reactivity by dysregulating the VDR ultimately to increase their chance of survival. Immune modulatory therapies that enhance VDR expression and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies have been engaged investigating the impact of VDR ex-pression in T cells and found that VDR expression and activity plays an important role in both T cell development, differentiation and effector function. In this review we will analyze current know-ledge of VDR regulation and function in T cells and discuss its importance for immune activity.

Quantitative susceptibility mapping across two clinical field strengths: Contrast-to-noise ratio enhancement at 1.5T.

Science.gov (United States)

Ippoliti, Matteo; Adams, Lisa C; Winfried, Brenner; Hamm, Bernd; Spincemaille, Pascal; Wang, Yi; Makowski, Marcus R

2018-04-16

Quantitative susceptibility mapping (QSM) is an MRI postprocessing technique that allows quantification of the spatial distribution of tissue magnetic susceptibility in vivo. Contributing sources include iron, blood products, calcium, myelin, and lipid content. To evaluate the reproducibility and consistency of QSM across clinical field strengths of 1.5T and 3T and to optimize the contrast-to-noise ratio (CNR) at 1.5T through bandwidth tuning. Prospective. Sixteen healthy volunteers (10 men, 6 women; age range 24-37; mean age 27.8 ± 3.2 years). 1.5T and 3T systems from the same vendor. Four spoiled gradient echo (SPGR) sequences were designed with different acquisition bandwidths. QSM reconstruction was achieved through a nonlinear morphology-enabled dipole inversion (MEDI) algorithm employing L1 regularization. CNR was calculated in seven regions of interest (ROIs), while reproducibility and consistency of QSM measurements were evaluated through voxel-based and region-specific linear correlation analyses and Bland-Altman plots. Interclass correlation, Wilcoxon rank sum test, linear regression analysis, Bland-Altman analysis, Welch's t-test. CNR analysis showed a statistically significant (P limits of agreement from -18.7 to 25.8 ppb) in the ROI-based analysis, while the correlation was found to be good for the voxel-based analysis of averaged maps (R ≥ 0.90, widest limits of agreement from -9.3 to 9.1 ppb). CNR of QSM images reconstructed from 1.5T acquisitions can be enhanced through bandwidth tuning. MEDI-based QSM reconstruction demonstrated to be reproducible and consistent both across field strengths (1.5T and 3T) and bandwidth variation. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

[Influence of staphylococcin T on Enterococcus sp. growth].

Science.gov (United States)

Białucha, Agata; Kozuszko, Sylwia; Gospodarek, Eugenia; Bugalski, Roman Marian; Gierlotka, Krzysztof

2007-01-01

Bacteriocins are ribosomally synthesised, extracellular bacterial products. Generally, spectrum of inhibition is limited to the same or closely related species to bacteriocin producer. Staphylococcin T is produced by Staphylococcus cohnii strain. The present study concerns influence of StT to 267 Enterococcus sp. strains growth isolated between 2003 and 2006 in Department of Microbiology University Hospital of dr. A. Jurasz in Bydgoszcz. S. cohnii T antagonistic ability evaluated towards bacteries on Mueller-Hinton Agar (bio Mérieux) in aerobic conditions. After 24 and 48 hours tested enterococci suspensions were plated perpendiculary. Susceptibility to antibiotics was assessed by disc diffusion method according to the guideless of Clinical and Laboratory Standards Institute and National Reference Centre for Antimicrobial Susceptibility. Among Enterococcus sp. strains tested 7.1% were sensitive to StT. The highest percentage of sensitive enterococci isolated from wound swabs, urine, blood and pus. Enterococcus faecium strains dominated (63.2%) among enterococci sensitive to StT. Moderate inhibition degree on S. cohnii T bacteriocin action was observed in majority sensitive enterococci strains. Enterococcus sp. sensitive to StT strains were frequently multidrug resistant (68.4%). According to the study results and increasing resistance to antibiotics, StT could be an alternative agent used to treat infections caused by Enterococcus sp.

Follow-up of intracranial aneurysms treated with detachable coils: comparison of 3D inflow MRA at 3T and 1.5T and contrast-enhanced MRA at 3T with DSA

International Nuclear Information System (INIS)

Ramgren, Birgitta; Siemund, Roger; Cronqvist, Mats; Undren, Per; Holtaas, Stig; Nilsson, Ola G.; Larsson, Elna-Marie

2008-01-01

The purpose of this prospective study was to compare 3T and 1.5T magnetic resonance angiography (MRA) with digital subtraction angiography (DSA) for the follow-up of endovascular treated intracranial aneurysms to assess the grade of occlusion. Thirty-seven patients with 41 aneurysms who had undergone endovascular treatment with detachable coils were included. MRA was performed on the same day using an eight-channel sensitivity encoding head-coil with 3D axial inflow technique. At 3T, a contrast-enhanced transverse 3D fast gradient echo acquisition was also performed. Most patients underwent DSA the following day. MRA scans and DSA were classified first independently by two neuroradiologists and an interventional neuroradiologist. Secondly, a consensus was done. Source images, maximum intensity projection, multiplanar reconstruction and volume rendering reconstructions were used for MRA evaluations. A modification of the Raymond classification, previously used for DSA evaluation of recanalization, was used. Statistical comparison of the consensus showed that 3T MRA with 3D axial inflow technique had better agreement with DSA (κ = 0.43) than 1.5T MRA(κ = 0.21) and contrast-enhanced MRA (CE-MRA) at 3T (κ = 0.17). The susceptibility artefacts from the coil mesh were significally smaller at 3T (p = 0.002-0.007) than at 1.5T. 3T MRA, using a sensitivity encoding head-coil, showed better agreement with DSA than 1.5T and CE-MRA at 3T for evaluation of aneurysms treated with endovascular coiling. (orig.)

New susceptibility loci associated with kidney disease in type 1 diabetes.

Directory of Open Access Journals (Sweden)

Niina Sandholm

2012-09-01

Full Text Available Diabetic kidney disease, or diabetic nephropathy (DN, is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D. Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8 and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9. Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1 pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7, a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Susceptibility of ternary aluminum alloys to cracking during solidification

International Nuclear Information System (INIS)

Liu, Jiangwei; Kou, Sindo

2017-01-01

The crack susceptibility map of a ternary Al alloy system provides useful information about which alloy compositions are most susceptible to cracking and thus should be avoided by using a filler metal with a significantly different composition. In the present study the crack susceptibility maps of ternary Al alloy systems were calculated based on the maximum |dT/d(f S ) 1/2 | as an index for the crack susceptibility, where T is temperature and f S fraction solid. Due to the complexity associated with ternary alloy solidification, commercial thermodynamic software Pandat and Al database PanAluminum, instead of analytical equations, were used to calculate f S as a function of T and hence the maximum |dT/d(f S ) 1/2 | for ternary Al-Mg-Si, Al-Cu-Mg and Al-Cu-Si alloy systems. A crack susceptibility map covering 121 alloy compositions was constructed for each of the three ternary alloy systems at each of the following three levels of back diffusion: no back diffusion, back diffusion under a 100 °C/s cooling rate, and back diffusion under 20° C/s. The location of the region of high crack susceptibility, which is the most important part of the map, was shown in each of the nine calculated maps. These locations were compared with those observed in crack susceptibility tests by previous investigators. With back diffusion considered, either under 20 or 100 °C/s, the agreement between the calculated and observed maps was good especially for Al-Mg-Si and Al-Cu-Mg. Thus, the maximum |dT/d(f S ) 1/2 | can be used as a crack susceptibility index to construct crack susceptibility maps for ternary Al alloys and to evaluate the effect of back diffusion on their crack susceptibility. - Graphical abstract: The crack susceptibility map of a ternary alloy system indicates the composition range most susceptible to cracking, which should be avoided in welding or casting. The crack susceptibility maps of ternary Al alloy systems Al-Mg-Si, Al-Cu-Mg and Al-Cu-Si were calculated based

Influence of Radiation Damage and Isochronal Annealing on the Magnetic Susceptibility of Pu1-xAmx Alloys

International Nuclear Information System (INIS)

McCall, Scott K.; Fluss, Michael J.; Chung, Brandon W.; Haire, Richard G.

2008-01-01

Results of radiation damage in Pu and Pu 1-x Am x alloys studied with magnetic susceptibility, χ(T), and resistivity are presented. Damage accumulated at low temperatures increases χ(T) for all measured alloys, with the trend generally enhanced as the lattice expands. There is a trend towards saturation observable in the damage induced magnetic susceptibility data. that is not evident in similar damage induced resistivity data taken on the same specimen. A comparison of isochronal annealing curves measured by both resistivity and magnetic susceptibility on a 4.3 at% Ga stabilized δ-Pu specimen show that Stage I annealing, where interstitials begin to move, is largely transparent to the magnetic measurement. This indicates that interstitials have little impact on the damage induced increase in the magnetic susceptibility. The isochronal annealing curves of the Pu 1-x Am x alloys do not show distinct annealing stages as expected for alloys. However, samples near 20% Am concentration show an unexpected increase in magnetization beginning when specimens are annealed to 35 K. This behavior is also reflected in a time dependent increase in the magnetic susceptibility of damaged specimens indicative of first order kinetics. These results suggest there may be a metastable phase induced by radiation damage and annealing in Pu 1-x Am x alloys. (authors)

A.c. susceptibility measurements in the presence of d.c. magnetic fields for Nd-Ba-Cu-O superconductors

International Nuclear Information System (INIS)

Watahiki, M.; Murakami, M.; Yoo, S.I.

1997-01-01

We report the temperature and magnetic field dependence of the complex a.c. susceptibility with bias d.c. magnetic fields for melt-processed Nd-Ba-Cu-O superconductor. The onset temperature (T onset ) of the real part of a.c. susceptibility shifted to a lower temperature with increasing d.c. magnetic field. The superconducting transition temperature (T c ) determined by d.c. magnetization measurements did not shift appreciably to a lower-temperature region with increasing d.c. magnetic field. The distinction between T onset and T c indicates that the a.c. susceptibility measurements detect the energy dissipation generated by the motion of flux lines. We have also measured flux profiles and found that there was no appreciable change in flux penetration below and above the peak field, which suggests that the peak effect in Nd-Ba-Cu-O is not due to the phase transition in the flux line lattice. (author)

The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

DEFF Research Database (Denmark)

Kaur, Simranjeet; Mirza, Aashiq H.; Brorsson, Caroline Anna

2016-01-01

-producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351...

MR imaging of cranial nerve lesions using six different high-resolution T1- and T2(*)-weighted 3D and 2D sequences

Energy Technology Data Exchange (ETDEWEB)

Seitz, J.; Held, P.; Strotzer, M.; Voelk, M.; Nitz, W.R.; Dorenbeck, U.; Feuerbach, S. [Univ. Hospital of Regensburg (Germany). Dept. of Diagnostic Radiology; Stamato, S. [Univ. of California, San Diego, CA (United States). Dept. of Radiology

2002-07-01

Purpose: To find a suitable high-resolution MR protocol for the visualization of lesions of all 12 cranial nerves. Material and Methods: Thirty-eight pathologically changed cranial nerves (17 patients) were studied with MR imaging at 1.5T using 3D T2*-weighted CISS, T1-weighted 3D MP-RAGE (without and with i.v. contrast medium), T2-weighted 3D TSE, T2-weighted 2D TSE and T1-weighted fat saturation 2D TSE sequences. Visibility of the 38 lesions of the 12 cranial nerves in each sequence was evaluated by consensus of two radiologists using an evaluation scale from 1 (excellently visible) to 4 (not visible). Results: The 3D CISS sequence provided the best resolution of the cranial nerves and their lesions when surrounded by CSF. In nerves which were not surrounded by CSF, the 2D T1-weighted contrast-enhanced fat suppression technique was the best sequence. Conclusions: A combination of 3D CISS, the 2D T1-weighted fat suppressed sequence and a 3D contrast-enhanced MP-RAGE proved to be the most useful sequence to visualize all lesions of the cranial nerves. For the determination of enhancement, an additional 3D MP-RAGE sequence without contrast medium is required. This sequence is also very sensitive for the detection of hemorrhage.

MR imaging of cranial nerve lesions using six different high-resolution T1- and T2(*)-weighted 3D and 2D sequences

International Nuclear Information System (INIS)

Seitz, J.; Held, P.; Strotzer, M.; Voelk, M.; Nitz, W.R.; Dorenbeck, U.; Feuerbach, S.; Stamato, S.

2002-01-01

Purpose: To find a suitable high-resolution MR protocol for the visualization of lesions of all 12 cranial nerves. Material and Methods: Thirty-eight pathologically changed cranial nerves (17 patients) were studied with MR imaging at 1.5T using 3D T2*-weighted CISS, T1-weighted 3D MP-RAGE (without and with i.v. contrast medium), T2-weighted 3D TSE, T2-weighted 2D TSE and T1-weighted fat saturation 2D TSE sequences. Visibility of the 38 lesions of the 12 cranial nerves in each sequence was evaluated by consensus of two radiologists using an evaluation scale from 1 (excellently visible) to 4 (not visible). Results: The 3D CISS sequence provided the best resolution of the cranial nerves and their lesions when surrounded by CSF. In nerves which were not surrounded by CSF, the 2D T1-weighted contrast-enhanced fat suppression technique was the best sequence. Conclusions: A combination of 3D CISS, the 2D T1-weighted fat suppressed sequence and a 3D contrast-enhanced MP-RAGE proved to be the most useful sequence to visualize all lesions of the cranial nerves. For the determination of enhancement, an additional 3D MP-RAGE sequence without contrast medium is required. This sequence is also very sensitive for the detection of hemorrhage

Magnetic susceptibility of LaxCe1-xF3 single crystals

International Nuclear Information System (INIS)

Paradowski, M.L.; Pacyna, A.W.; Bombik, A.; Korczak, W.; Korczak, S.Z.

2000-01-01

The magnetic susceptibility of La x Ce 1-x F 3 single crystals, for 0 eff and paramagnetic Curie temperature θ p have been obtained, using the Curie-Weiss law in the temperature range 100-300 K. The interconfiguration excited energy E ex , the spin-fluctuation temperature T sf , and the g-values, corresponding to three Kramers doublets in the 2 F 5/2 ground multiplet of Ce 3+ ion in La x Ce 1-x F 3 have been determined, using quantum theory of paramagnetic susceptibility. The mixed-valent and crystal field effects influence significantly the g-values. The effect of the dilution of the paramagnetic Ce 3+ ions with diamagnetic La 3+ ions is also discussed

Calculation of the energy of particles emitted by the reactions {sup 3}{sub 1}T (d,n) {sup 4}{sub 2}He, D (d,n) {sup 3}{sub 2}He and D (d,p) T; Calcul de l'energie des particules emises par les reactions {sup 3}{sub 1}T (d,n) {sup 4}{sub 2}He, D (d,n) {sup 3}{sub 2}He et D (d,p) T

Energy Technology Data Exchange (ETDEWEB)

Oria, M; Sorriaux, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1965-07-01

With a view to ease the work of research workers using 150 kV electrostatic accelerators, we have calculated the energy and the emission angle of particles emitted during the reactions {sub 1}{sup 3}T(d,n){sub 2}{sup 4}He, {sub 1}{sup 2}D(d,n){sub 2}{sup 3}He and {sub 1}{sup 2}D(d,p){sub 1}{sup 3}T. The results are classified in tables and arranged according to the acceleration energy of the deuterons. Since the energies considered are relatively low we have limited our study to the non-relativistic domain; this simplification results in a maximum energy variation with respect to the real energy values of 1 per cent. We give also two curves representing the variations in the total cross-sections for the reactions T (d,n){sub 2}{sup 4}He and D (d,n){sub 2}{sup 3}He. (authors) [French] De facon a faciliter la tache des experimentateurs utilisant des accelerateurs electrostatiques de 150 kV, nous avons calcule l'energie et l'angle d'emission des particules emises lors des reactions {sub 1}{sup 3}T(d,n){sub 2}{sup 4}He, {sub 1}{sup 2}D(d,n){sub 2}{sup 3}He and {sub 1}{sup 2}D(d,p){sub 1}{sup 3}T. Les resultats ont ete classes dans des tableaux, et ordonnes en fonction de l'energie d'acceleration des deuterons. Les energies considerees etant relativement peu elevees, nous avons limite notre etude au domaine non relativiste, cette simplification n'entraine qu'une variation maximale de 1 pour cent sur les valeurs reelles des energies. Nous avons joint a ce calcul deux courbes representant la variation des sections efficaces totales des reactions T (d,n){sub 2}{sup 4}He et D (d,n){sub 2}{sup 3}He. (auteurs)

T-duality of Green-Schwarz superstrings on AdS_d×S"d×M"1"0"−"2"d

International Nuclear Information System (INIS)

Abbott, Michael C.; Murugan, Jeff; Penati, Silvia; Pittelli, Antonio; Sorokin, Dmitri; Sundin, Per; Tarrant, Justine; Wolf, Martin; Wulff, Linus

2015-01-01

We verify the self-duality of Green-Schwarz supercoset sigma models on AdS_d×S"d backgrounds (d=2,3,5) under combined bosonic and fermionic T-dualities without gauge fixing kappa symmetry. We also prove this property for superstrings on AdS_d×S"d×S"d(d=2,3) described by supercoset sigma models with the isometries governed by the exceptional Lie supergroups D(2,1;α) (d=2) and D(2,1;α)×D(2,1;α) (d=3), which requires an additional T-dualisation along one of the spheres. Then, by taking into account the contribution of non-supercoset fermionic modes (up to the second order), we provide evidence for the T-self-duality of the complete type IIA and IIB Green-Schwarz superstring theory on AdS_d×S"d×T"1"0"−"2"d (d=2,3) backgrounds with Ramond-Ramond fluxes. Finally, applying the Buscher-like rules to T-dualising supergravity fields, we prove the T-self-duality of the whole class of the AdS_d×S"d×M"1"0"−"2"d superbackgrounds with Ramond-Ramond fluxes in the context of supergravity.

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility.

Science.gov (United States)

Han, Xia; Liu, Lili; Niu, Jiamin; Yang, Jun; Zhang, Zengtang; Zhang, Zhiqiang

2015-01-01

Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.

Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers

DEFF Research Database (Denmark)

Onengut-Gumuscu, Suna; Chen, Wei-Min; Burren, Oliver

2015-01-01

Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array...... and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter......, the Immunochip, was developed, from which we identified four new T1D-associated regions (P comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis...

Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota.

Science.gov (United States)

Mullaney, Jane A; Stephens, Juliette E; Costello, Mary-Ellen; Fong, Cai; Geeling, Brooke E; Gavin, Patrick G; Wright, Casey M; Spector, Timothy D; Brown, Matthew A; Hamilton-Williams, Emma E

2018-02-17

Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort. Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse. These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.

Experimental validation of Villain's conjecture about magnetic ordering in quasi-1D helimagnets

International Nuclear Information System (INIS)

Cinti, F.; Rettori, A.; Pini, M.G.; Mariani, M.; Micotti, E.; Lascialfari, A.; Papinutto, N.; Amato, A.; Caneschi, A.; Gatteschi, D.; Affronte, M.

2010-01-01

Low-temperature magnetic susceptibility, zero-field muon spin resonance and specific heat measurements have been performed in the quasi-one-dimensional (1D) molecular helimagnetic compound Gd(hfac) 3 NITEt. The specific heat presents two anomalies at T 0 =2.19(2)K and T N =1.88(2)K, while susceptibility and zero-field muon spin resonance show anomalies only at T N =1.88(2)K. The results suggest an experimental validation of Villain's conjecture of a two-step magnetic ordering in quasi-1D XY helimagnets: the paramagnetic phase and the helical spin solid phases are separated by a chiral spin liquid, where translational invariance is broken without violation of rotational invariance.

Measurement of weak electric currents in copper wire phantoms using MRI: influence of susceptibility enhancement.

Science.gov (United States)

Huang, Ruiwang; Posnansky, Oleg; Celik, Abdullah; Oros-Peusquens, Ana-Maria; Ermer, Veronika; Irkens, Marco; Wegener, H-Peter; Shah, N Jon

2006-08-01

The use of magnetic resonance imaging (MRI)-based methods for the direct detection of neuronal currents is a topic of intense investigation. Much experimental work has been carried out with the express aim of establishing detection thresholds and sensitivity to flowing currents. However, in most of these experiments, magnetic susceptibility enhancement was ignored. In this work, we present results that show the influence of a susceptibility artefact on the detection threshold and sensitivity. For this purpose, a novel phantom, consisting of a water-filled cylinder with two wires of different materials connected in series, was constructed. Magnitude MR images were acquired from a single slice using a gradient-echo echo planar imaging (EPI) sequence. The data show that the time course of the detected MR signal magnitude correlates very well with the waveform of the input current. The effect of the susceptibility artefacts arising from the two different wires was examined by comparing the magnitudes of the MR signals at different voxel locations. Our results indicate the following: (1) MR signal enhancement arising from the magnetic susceptibility effect influences the detection sensitivity of weak current; (2) the detection threshold and sensitivity are phantom-wire dependent; (3) sub-mu A electric current detection in a phantom is possible on a 1.5-T MR scanner in the presence of susceptibility enhancement.

Anti-cytokine therapies in T1D

DEFF Research Database (Denmark)

Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

2013-01-01

Therapeutic targeting of proinflammatory cytokines is clinically beneficial in several autoimmune disorders. Several of these cytokines are directly implicated in the pathogenesis of type 1 diabetes, suggesting opportunities for design of clinical trials in type 1 diabetes that incorporate select...... suitable for modulating the immune response in T1D....

MAVS is not a Likely Susceptibility Locus for Addison's Disease and Type 1 Diabetes.

Science.gov (United States)

Zurawek, Magdalena; Fichna, Marta; Kazimierska, Marta; Fichna, Piotr; Dzikiewicz-Krawczyk, Agnieszka; Przybylski, Grzegorz; Ruchala, Marek; Nowak, Jerzy

2017-06-01

Mitochondrial antiviral signaling (MAVS) protein is an intracellular adaptor molecule, downstream of viral sensors, retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs). Impaired antiviral cell signaling might contribute to autoimmunity. Studies have recently shown variations in genes encoding RLRs as risk factors for autoimmune diseases. We investigated whether MAVS coding polymorphisms are associated with Addison's disease (AD) and type 1 diabetes (T1D) in Polish population. We genotyped 140 AD, 532 T1D patients and 600 healthy controls for MAVS rs17857295, rs7262903, rs45437096 and rs7269320. Genotyping was performed by TaqMan assays. Distribution of the MAVS genotypes and alleles did not reveal significant differences between patients and controls (p > 0.05). This analysis did not indicate the association of the MAVS locus with susceptibility to AD and T1D.

In vivo 1D and 2D correlation MR spectroscopy of the soleus muscle at 7T

Science.gov (United States)

Ramadan, Saadallah; Ratai, Eva-Maria; Wald, Lawrence L.; Mountford, Carolyn E.

2010-05-01

AimThis study aims to (1) undertake and analyse 1D and 2D MR correlation spectroscopy from human soleus muscle in vivo at 7T, and (2) determine T1 and T2 relaxation time constants at 7T field strength due to their importance in sequence design and spectral quantitation. MethodSix healthy, male volunteers were consented and scanned on a 7T whole-body scanner (Siemens AG, Erlangen, Germany). Experiments were undertaken using a 28 cm diameter detunable birdcage coil for signal excitation and an 8.5 cm diameter surface coil for signal reception. The relaxation time constants, T1 and T2 were recorded using a STEAM sequence, using the 'progressive saturation' method for the T1 and multiple echo times for T2. The 2D L-Correlated SpectroscopY (L-COSY) method was employed with 64 increments (0.4 ms increment size) and eight averages per scan, with a total time of 17 min. ResultsT1 and T2 values for the metabolites of interest were determined. The L-COSY spectra obtained from the soleus muscle provided information on lipid content and chemical structure not available, in vivo, at lower field strengths. All molecular fragments within multiple lipid compartments were chemically shifted by 0.20-0.26 ppm at this field strength. 1D and 2D L-COSY spectra were assigned and proton connectivities were confirmed with the 2D method. ConclusionIn vivo 1D and 2D spectroscopic examination of muscle can be successfully recorded at 7T and is now available to assess lipid alterations as well as other metabolites present with disease. T1 and T2 values were also determined in soleus muscle of male healthy volunteers.

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

Science.gov (United States)

Niu, Qingli; Hou, Wei; Churchyard, Gavin; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Franchini, Genoveffa

2018-01-01

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination. PMID:29474461

Comparison of 3T and 7T susceptibility-weighted angiography of the substantia nigra in diagnosing Parkinson disease.

Science.gov (United States)

Cosottini, M; Frosini, D; Pesaresi, I; Donatelli, G; Cecchi, P; Costagli, M; Biagi, L; Ceravolo, R; Bonuccelli, U; Tosetti, M

2015-03-01

Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study. © 2015 by American Journal of Neuroradiology.

LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

Science.gov (United States)

Zhang, Zhuorong; Chang, Yitian; Jia, Wei; Zhang, Jiao; Zhang, Ruizhong; Zhu, Jinhong; Yang, Tianyou; Xia, Huimin; Zou, Yan; He, Jing

2018-02-28

Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95% confidence interval (CI) =1.06-3.06, P =0.029; TT/CT compared with CC: adjusted OR =1.31, 95% CI =1.02-1.67, P =0.033; and T compared with C: adjusted OR =1.29, 95% CI =1.06-1.58, P =0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR =1.51, 95% CI =1.06-2.14, P =0.021) and International Neuroblastoma Staging System (INSS) stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P =0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings. © 2018 The Author(s).

Dopamine receptor D3 expressed on CD4+ T cells favors neurodegeneration of dopaminergic neurons during Parkinson's disease.

Science.gov (United States)

González, Hugo; Contreras, Francisco; Prado, Carolina; Elgueta, Daniela; Franz, Dafne; Bernales, Sebastián; Pacheco, Rodrigo

2013-05-15

Emerging evidence has demonstrated that CD4(+) T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4(+) T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4(+) T cells. In this study, we examined the role of D3R expressed on CD4(+) T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4(+) T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4(+) T cells but not when transferred with D3R-deficient CD4(+) T cells. In agreement, experiments analyzing activation and differentiation of CD4(+) T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4(+) T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

The vitamin d receptor and T cell function

DEFF Research Database (Denmark)

Kongsbak, Martin; Levring, Trine B; Geisler, Carsten

2013-01-01

The vitamin D receptor (VDR) is a nuclear, ligand-dependent transcription factor that in complex with hormonally active vitamin D, 1,25(OH)2D3, regulates the expression of more than 900 genes involved in a wide array of physiological functions. The impact of 1,25(OH)2D3-VDR signaling on immune...... function has been the focus of many recent studies as a link between 1,25(OH)2D3 and susceptibility to various infections and to development of a variety of inflammatory diseases has been suggested. It is also becoming increasingly clear that microbes slow down immune reactivity by dysregulating the VDR...... ultimately to increase their chance of survival. Immune modulatory therapies that enhance VDR expression and activity are therefore considered in the clinic today to a greater extent. As T cells are of great importance for both protective immunity and development of inflammatory diseases a variety of studies...

The perceived influence of cigarette advertisements and smoking susceptibility among seventh graders.

Science.gov (United States)

Borzekowski, D L; Flora, J A; Feighery, E; Schooler, C

1999-01-01

A perceptual bias, the third person effect, has been observed where individuals believe themselves to differ from others regarding the perceived influence of media messages. Given the frequency with which youth encounter prosmoking messages and the reported negative effects of these messages, it is of value to study whether youth perceive cigarette advertisements to influence themselves and their friends and peers. This study examined the associations between exposure to social and information prosmoking environments, the perceived influence of cigarette advertisements on self, best friends, and other youth, and smoking susceptibility. A sample of 571 seventh graders completed surveys on tobacco advertisements and promotions. Using Student's-t, chi-square, ANOVA tests and proportional odds models, we found significant associations between perceived influence of cigarette advertisements and exposure to social and information prosmoking environments as well as smoking susceptibility. These data suggest that youth be taught that everyone is vulnerable to the tobacco industry's strategies and be given skills to resist prosmoking advertising.

Non HLA genetic markers association with type-1 diabetes mellitus ...

African Journals Online (AJOL)

The currently available data identified IDDM1 and IDDM2 as 2 susceptibility loci for type 1 diabetes (T1D). The major histocompatibility complex (MHC)/HLA region referred to as IDDM1 contains several 100 genes known to have a great influence on T1D risk. Within IDDM2, a minisatellite variable number of tandem repeats ...

OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

LENUS (Irish Health Repository)

O'Brien, M

2012-02-01

BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

Experimental investigation of temperature dependence of the magnetic susceptibility (T) of manganites La1-xAxMnO3

International Nuclear Information System (INIS)

Salakhitdinova, M.; Kuvandikov, O.; Shakarov, Kh.; Shodiev, Z.

2007-01-01

Full text: he interest to lanthanoid manganites is based that enormous magnetoresistance is found in them and this materials are capable to test diverse structural and magnetic phase transformations. The work is devoted to experimental investigation of temperature dependence of the magnetic susceptibility (T) of manganites La 1-x A x MnO 3 which doped with Ag, K, Sr metals in wide temperature interval 50-8500 C, as well as to determination of their magnetic characteristics from this dependence. The dependence (T) was measured by the Faraday method with high-temperature magnetic pendulum balance in the atmosphere of refined helium. Maximal relative error of the measurements did not exceed 3 %. The analysis of experimental (T) dependence of investigated manganites has shown that the rise of stoichiometric rate of doped metals the temperature dependence of magnetic susceptibility of manganites monotonously is decreased. (authors)

Assessment of CD4+ T cell responses to glutamic acid decarboxylase 65 using DQ8 tetramers reveals a pathogenic role of GAD65 121-140 and GAD65 250-266 in T1D development.

Directory of Open Access Journals (Sweden)

I-Ting Chow

Full Text Available Susceptibility to type 1 diabetes (T1D is strongly associated with MHC class II molecules, particularly HLA-DQ8 (DQ8: DQA1*03:01/DQB1*03:02. Monitoring T1D-specific T cell responses to DQ8-restricted epitopes may be key to understanding the immunopathology of the disease. In this study, we examined DQ8-restricted T cell responses to glutamic acid decarboxylase 65 (GAD65 using DQ8 tetramers. We demonstrated that GAD65 121-140 and GAD65 250-266 elicited responses from DQ8+ subjects. Circulating CD4+ T cells specific for these epitopes were detected significantly more often in T1D patients than in healthy individuals after in vitro expansion. T cell clones specific for GAD65 121-140 and GAD65 250-266 carried a Th1-dominant phenotype, with some of the GAD65 121-140-specific T cell clones producing IL-17. GAD65 250-266-specific CD4+ T cells could also be detected by direct ex vivo staining. Analysis of unmanipulated peripheral blood mononuclear cells (PBMCs revealed that GAD65 250-266-specific T cells could be found in both healthy and diabetic individuals but the frequencies of specific T cells were higher in subjects with type 1 diabetes. Taken together, our results suggest a proinflammatory role for T cells specific for DQ8-restricted GAD65 121-140 and GAD65 250-266 epitopes and implicate their possible contribution to the progression of T1D.

The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst formation is influenced by the lineage of infective Toxoplasma gondii strain

Directory of Open Access Journals (Sweden)

Marianne G. Resende

2008-03-01

Full Text Available Toxoplasma gondii strains displaying the Type I/III genotype are associated with acquired ocular toxoplasmosis in humans. Here, we used a mice model to characterize some immunological mechanisms involved in host resistance to infection with such strains. We have chosen the Type I/III strains D8, G2 and P-Br, which cause a chronic infection in mice that resembles human toxoplamosis. Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all three parasite strains. This finding indicates the importance of innate mechanisms in controlling infection. On the other hand, MHC haplotype did not influenced resistance/susceptibility; since mice lineages displaying a same genetic background but different MHC haplotypes (H2b or H2d developed similar mortality and cyst numbers after infection with those strains. In contrast, the C57BL/6 genetic background, and not MHC haplotype, was critical for development of intestinal inflammation caused by any of the studied strains. Finally, regarding effector mechanisms, weobserved that B and CD8+ T lymphocytes controlled survival,whereas the inducible nitric oxide synthase influenced cyst numbers in brains of mice infected with Type I/III strains. These findings are relevant to further understanding of the immunologic mechanisms involved in host protection and pathogenesis during infection with T. gondii.Cepas de Toxoplasma gondii que apresentam o genótipo I/III são associadas a toxoplasmose ocular adquirida em humanos. No presente trabalho, nós utilizamos um modelo da doença em camundongos para caracterizar mecanismos imunológicos envolvidos na resistência do hospedeiro à infecção por aquelas cepas. Escolhemos as cepas D8, G2 e P-Br, que causam infecção crônica em camundongos, semelhante à toxoplasmose humana. Camundongos deficientes em MyD88, IFN-G e IL-12 foram susceptíveis a infecções com todas as três linhagens do parasita. Esses dados indicam a importância de mecanismos

1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease

DEFF Research Database (Denmark)

Bartels, Lars Erik; Jørgensen, Søren Peter; Agnholt, Jørgen

2007-01-01

,25-dihydroxyvitamin D3 with and without DEX could induce IL-10 production, downregulate pro-inflammatory Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha production, and influence cell kinetics in peripheral CD4+ T cells from CD patients. METHODS: CD4+ T cells were separated from peripheral blood from CD......BACKGROUND AND AIM: In Crohn's disease (CD), epidemiological data and animal studies suggest that vitamin D (vitD) has protective immune-modulating properties. 1,25-dihydroxyvitamin D3 and dexamethasone (DEX) induce interleukin (IL)-10 productions in healthy controls (HC) T cells. We studied if 1...... patients and HC. Cells were activated by anti-CD3 and anti-CD28 in the presence of 1,25-dihydroxyvitamin D3 and/or DEX. Cytokine levels, proliferation, and apoptosis were measured following 7 days of culture. RESULTS: In T cells from CD patients, 1,25-dihydroxyvitamin D3 and DEX increased IL-10 production...

Experimental validation of Villain's conjecture about magnetic ordering in quasi-1D helimagnets

Energy Technology Data Exchange (ETDEWEB)

Cinti, F., E-mail: fabio.cinti@fi.infn.i [CNISM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); CNR-INFM S3 National Research Center, I-41100 Modena (Italy); Rettori, A. [CNISM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); CNR-INFM S3 National Research Center, I-41100 Modena (Italy); Pini, M.G. [ISC-CNR, Via Madonna del Piano 10, I-50019 Sesto Fiorentino (Italy); Mariani, M.; Micotti, E. [Department of Physics A. Volta and CNR-INFM, University of Pavia, Via Bassi 6, I-27100 Pavia (Italy); Lascialfari, A. [Department of Physics A. Volta and CNR-INFM, University of Pavia, Via Bassi 6, I-27100 Pavia (Italy); Institute of General Physiology and Biological Chemistry, University of Milano, Via Trentacoste 2, I-20134 Milano (Italy); CNR-INFM S3 National Research Center, I-41100 Modena (Italy); Papinutto, N. [CIMeC, University of Trento, Via delle Regole, 101 38060 Mattarello (Italy); Department of Physics A. Volta and CNR-INFM, University of Pavia, Via Bassi 6, I-27100 Pavia (Italy); Amato, A. [Paul Scherrer Institute, CH-5232 Villingen PSI (Switzerland); Caneschi, A.; Gatteschi, D. [INSTM R.U. Firenze and Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Italy); Affronte, M. [CNR-INFM S3 National Research Center, I-41100 Modena (Italy); Department of Physics, University of Modena and Reggio Emilia Via Campi 213/A, I-41100 Modena (Italy)

2010-05-15

Low-temperature magnetic susceptibility, zero-field muon spin resonance and specific heat measurements have been performed in the quasi-one-dimensional (1D) molecular helimagnetic compound Gd(hfac){sub 3}NITEt. The specific heat presents two anomalies at T{sub 0}=2.19(2)K and T{sub N}=1.88(2)K, while susceptibility and zero-field muon spin resonance show anomalies only at T{sub N}=1.88(2)K. The results suggest an experimental validation of Villain's conjecture of a two-step magnetic ordering in quasi-1D XY helimagnets: the paramagnetic phase and the helical spin solid phases are separated by a chiral spin liquid, where translational invariance is broken without violation of rotational invariance.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients.

Science.gov (United States)

Aly, Dalia Gamal; Salem, Samar Abdallah; Amr, Khalda Sayed; El-Hamid, Mahmoud Fawzy Abd

2018-01-01

The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (Pvitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. Small sample size of patients. This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

Science.gov (United States)

Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

2014-09-01

l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Contrast-enhanced 3T MR perfusion of musculoskeletal tumours. T1 value heterogeneity assessment and evaluation of the influence of T1 estimation methods on quantitative parameters

Energy Technology Data Exchange (ETDEWEB)

Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Verbizier, Jacques de; Blum, Alain [Hopital Central, CHRU-Nancy, Service d' Imagerie Guilloz, Nancy (France); Chen, Bailiang; Beaumont, Marine [Universite de Lorraine, Laboratoire IADI, UMR S 947, Nancy (France); Badr, Sammy; Cotten, Anne [CHRU Lille Centre de Consultations et d' Imagerie de l' Appareil Locomoteur, Department of Radiology and Musculoskeletal Imaging, Lille (France)

2017-12-15

To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. (orig.)

Time as An Important Soil-Forming Factor Influencing Modern and Ancient Magnetic Susceptibility Enhancement Along the Delaware River Valley, USA

Science.gov (United States)

Stinchcomb, G. E.; Peppe, D. J.; Driese, S. G.

2011-12-01

Magnetic susceptibility is an increasingly popular low-cost method for rapidly assessing paleoclimate and paleoenvironmental impact on buried soils. The goal of this study is to determine the primary influence(s) on soil magnetic susceptibility along floodplain, terrace and upland soils in the middle Delaware River Valley, USA, using environmental magnetic, pedologic, and stratigraphic techniques. Two-hundred thirty samples were collected from age-constrained sandy, quartz-rich, floodplain, terrace, and upland soils (Entisols, Inceptisols). A Kruskal-Wallis (K-W) and post-hoc Tukey-Kramer (T-K) (α=0.05) multiple comparisons analysis on 176 mass-specific low-field susceptibility (Xlf) assays show that A and B horizons are magnetically enhanced compared to C and E horizons (ptesting show that Xlf results, when grouped by floodplain-terrace designation (i.e., chronofunction) are significantly different (p<0.0001). The older T3 terrace and upland Xlf values (0.34±0.14 10^-6 m^3 kg^-1) are greater than the younger T2 terrace (0.18±0.06 10^-6 m^3 kg^-1) values, which are greater than modern floodplain (0.09±0.01 10^-6 m^3 kg^-1) Xlf values. These data suggest that longer intervals of soil formation enhance the Χlf value. This hypothesis is further supported when 159 Xlf values are plotted vs. age for the entire Holocene. A locally-weighted regression smoothing curve (LOESS) shows two distinct intervals of magnetic enhancement during previously established dry intervals, the early and late-middle Holocene. We hypothesize that prolonged drought during the early and middle Holocene reduced flood frequency and magnitude and the likelihood of soil burial, resulting in longer soil forming intervals and higher Xlf values. Although precipitation influences the Xlf signature, the results from this study suggest that the magnetic susceptibility values of well-drained buried floodplain soils along the Delaware River Valley are partly a function of time.

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

International Nuclear Information System (INIS)

White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

2014-01-01

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

Energy Technology Data Exchange (ETDEWEB)

White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

2014-07-15

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

International Nuclear Information System (INIS)

Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H.; Walter, Oliver; Gieseke, Juergen

2007-01-01

The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

Energy Technology Data Exchange (ETDEWEB)

Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H. [University of Bonn, Department of Radiology, Bonn (Germany); Walter, Oliver [Leibniz-Institute for Science Education, Kiel (Germany); Gieseke, Juergen [University of Bonn, Department of Radiology, Bonn (Germany); Philips Medical Systems, Hamburg (Germany)

2007-05-15

The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

Magnetic susceptibility measurement using 3D NMR

Czech Academy of Sciences Publication Activity Database

Marcon, P.; Bartušek, Karel; Kořínek, Radim

2011-01-01

Roč. 24, Suppl. 1 (2011), s. 381-382 ISSN 0968-5243. [ESMRMB 2011 Congress. 06.10.2011-08.10.2011, Leipzig] R&D Projects: GA ČR GAP102/11/0318 Institutional research plan: CEZ:AV0Z20650511 Keywords : MRI * artifact correction * magnetic susceptibility * gradient echo Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

International Nuclear Information System (INIS)

Buchbender, Christian; Scherer, Axel; Kroepil, Patric; Quentin, Michael; Reichelt, Dorothea C.; Lanzman, Rotem S.; Mathys, Christian; Blondin, Dirk; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk; Koerbl, Birthe; Bittersohl, Bernd; Zilkens, Christoph; Hofer, Matthias; Schneider, Matthias; Ostendorf, Benedikt

2012-01-01

To prospectively evaluate four non-invasive markers of cartilage quality - T2* mapping, native T1 mapping, dGEMRIC and ΔR1 - in healthy volunteers and rheumatoid arthritis (RA) patients. Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1 Gd ). The difference in the longitudinal relaxation rate induced by gadolinium (ΔR1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. dGEMRIC (AUC 0.81) and ΔR1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of ΔR1 does not increase the diagnostic value of dGEMRIC. (orig.)

Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, {delta}R1 and value of pre-contrast imaging

Energy Technology Data Exchange (ETDEWEB)

Buchbender, Christian; Scherer, Axel; Kroepil, Patric; Quentin, Michael; Reichelt, Dorothea C.; Lanzman, Rotem S.; Mathys, Christian; Blondin, Dirk; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Koerbl, Birthe [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany); Heinrich-Heine-University, Leibniz Centre for Diabetes Research, Institute of Biometrics and Epidemiology, German Diabetes Centre, Duesseldorf (Germany); Bittersohl, Bernd; Zilkens, Christoph [Heinrich-Heine-University, Department of Orthopaedics, Medical Faculty, Duesseldorf (Germany); Hofer, Matthias [Heinrich-Heine-University, Medical Education Group, Medical School, Duesseldorf (Germany); Schneider, Matthias; Ostendorf, Benedikt [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany)

2012-06-15

To prospectively evaluate four non-invasive markers of cartilage quality - T2* mapping, native T1 mapping, dGEMRIC and {delta}R1 - in healthy volunteers and rheumatoid arthritis (RA) patients. Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1{sub Gd}). The difference in the longitudinal relaxation rate induced by gadolinium ({delta}R1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. dGEMRIC (AUC 0.81) and {delta}R1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of {delta}R1 does not increase the diagnostic value of dGEMRIC. (orig.)

STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes.

Science.gov (United States)

Lee, Hye-Soon; Park, Hyewon; Yang, Seiwon; Kim, Dukhee; Park, Yongsoo

2008-12-01

In an effort to discover non-HLA genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 nondiabetic controls in Korea. Four SNPs on chromosome 2q, which were recently found to be associated with rheumatoid arthritis, were examined for association and linkage disequilibrium. We found that neither alleles or genotypes among all four SNPs nor reconstructed haplotypes of the three SNPs within the same LD block (rs7574865, rs8179673, and rs10181656) were associated with susceptibility to T1D. When we stratified T1D patients into early-onset and late-onset subgroups on the basis of fewer or more than 7.8 years of age at diagnosis, however, the minor alleles of three SNPs (rs7574865, rs8179673, and rs10181656) showed a significant association with susceptibility to T1D in the early-onset subgroup (i.e., rs7574865, OR = 1.44 [1.03-2.01], P rs7574865, rs8179673, and rs10181656) showed very comparable degrees of risk for T1D. The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. Recognizing that only the early-onset cases might represent the true autoimmune T1D in Asian populations, we see that STAT4 alleles and haplotype might influence cytokine signaling and, therefore, development of T1D.

Monte Carlo study of the influence of energy spectra, mesh size, high Z element on dose and PVDR based on 1-D and 3-D heterogeneous mouse head phantom for Microbeam Radiation Therapy.

Science.gov (United States)

Lin, Hui; Jing, Jia; Xu, Liangfeng; Mao, Xiaoli

2017-12-01

To evaluate the influence of energy spectra, mesh sizes, high Z element on dose and PVDR in Microbeam Radiation Therapy (MRT) based on 1-D analogy-mouse-head-model (1-D MHM) and 3-D voxel-mouse-head-phantom (3-D VMHP) by Monte Carlo simulation. A Microbeam-Array-Source-Model was implemented into EGSnrc/DOSXYZnrc. The microbeam size is assumed to be 25μm, 50μm or 75μm in thickness and fixed 1mm in height with 200μmc-t-c. The influence of the energy spectra of ID17@ESRF and BMIT@CLS were investigated. The mesh size was optimized. PVDR in 1-D MHM and 3-D VMHP was compared with the homogeneous water phantom. The arc influence of 3-D VMHP filled with water (3-D VMHWP) was compared with the rectangle phantom. PVDR of the lower BMIT@CLS spectrum is 2.4times that of ID17@ESRF for lower valley dose. The optimized mesh is 5µm for 25µm, and 10µm for 50µm and 75µm microbeams with 200µmc-t-c. A 500μm skull layer could make PVDR difference up to 62.5% for 1-D MHM. However this influence is limited (influence is limited for the more depth (influence of 3-D heterogeneous media. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Evaluation of semisolid agar method for antifungal susceptibility test of T. rubrum

Directory of Open Access Journals (Sweden)

Sultana Razia

2016-08-01

Full Text Available Background: With increasing fungal disease many newer antifungal drugs are available with different spectrum of activ­ity. Antifungal susceptibility test will help clinicians for selection of effective drug and thereby treatment of patient. Objective: The study was undertaken to perform a simple screening drug susceptibility test of T. rnbrum by Semi Solid Agar Antifungal Susceptibility (SAAS Method: Perfonnance of susceptibility method was assessed by comparing the MICs of three commonly prescribed antifungal agents namely- tluconazole (FCZ, itraconazole (ITZ and terbinafine (TER to the CLSI (Clinical and Laboratory Standard Institute recommended M-38, a broth microdilution method. Results: In SAAS method, among twenty nine T. rubrum, twenty five (86.2% were susceptible (MIC range 0.5-64 µg/ml to Fluconazole (FCZ and four (13.7% were resistant (MIC value >64 µg/ml. In broth microdilution method, among twenty nine T. rubrum, twenty six (89.6% were susceptible (MIC range 0.3-64 µg/ml to FCZ and three (10.3% were resistant (MIC value >64 µg/ml. In case of both ITZ and TER, all were susceptible (MIC range 0.3-64 µg/ml to both methods. The SAAS method demonstrated the susceptibility pattern of T. rubrum against FCZ, ITZ and TER usually within 72 to 96 hours after organism isolation and results were concordance with the results of CLSI broth microdilution method. Conclusion: Though it is a newer method with proper standardization of the test method, SAAS method is simple and easily applicable screening method for susceptibility testing of antifungal agents against dermatophytes in any microbiology laboratories.

Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

Science.gov (United States)

Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

2017-12-01

To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

Comparison between gadolinium-enhanced 2D T1-weighted gradient-echo and spin-echo sequences in the detection of active multiple sclerosis lesions on 3.0T MRI

Energy Technology Data Exchange (ETDEWEB)

Aymerich, F.X. [Hospital Universitari Vall d' Hebron, Universitat Autonoma de Barcelona, MR Unit. Department of Radiology (IDI), Barcelona (Spain); Universitat Politecnica de Catalunya - Barcelona Tech (UPC), Department of Automatic Control (ESAII), Barcelona (Spain); Auger, C.; Alcaide-Leon, P.; Pareto, D.; Huerga, E.; Corral, J.F.; Mitjana, R.; Rovira, A. [Hospital Universitari Vall d' Hebron, Universitat Autonoma de Barcelona, MR Unit. Department of Radiology (IDI), Barcelona (Spain); Sastre-Garriga, J.; Montalban, X. [Hospital Universitari Vall d' Hebron, Universitat Autonoma de Barcelona, Centre d' Esclerosi Multiple de Catalunya (Cemcat), Department of Neurology/Neuroimmunology, Barcelona (Spain)

2017-04-15

To compare the sensitivity of enhancing multiple sclerosis (MS) lesions in gadolinium-enhanced 2D T1-weighted gradient-echo (GRE) and spin-echo (SE) sequences, and to assess the influence of visual conspicuity and laterality on detection of these lesions. One hundred MS patients underwent 3.0T brain MRI including gadolinium-enhanced 2D T1-weighted GRE and SE sequences. The two sets of contrast-enhanced scans were evaluated in random fashion by three experienced readers. Lesion conspicuity was assessed by the image contrast ratio (CR) and contrast-to-noise ratio (CNR). The intracranial region was divided into four quadrants and the impact of lesion location on detection was assessed in each slice. Six hundred and seven gadolinium-enhancing MS lesions were identified. GRE images were more sensitive for lesion detection (0.828) than SE images (0.767). Lesions showed a higher CR in SE than in GRE images, whereas the CNR was higher in GRE than SE. Most misclassifications occurred in the right posterior quadrant. The gadolinium-enhanced 2D T1-weighted GRE sequence at 3.0T MRI enables detection of enhancing MS lesions with higher sensitivity and better lesion conspicuity than 2D T1-weighted SE. Hence, we propose the use of gadolinium-enhanced GRE sequences rather than SE sequences for routine scanning of MS patients at 3.0T. (orig.)

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

Science.gov (United States)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

Structure, resistivity, critical field, specific-heat jump at Tc, Meissner effect, a.c. and d.c. Susceptibility of the high-temperature superconductor La2-xSrxCuO4

International Nuclear Information System (INIS)

Decroux, M.; Junod, A.; Bezinge, A.

1987-01-01

The temperature dependence of the resistivity, the magnetic properties and the specific heat were investigated on sintered samples of La 1.85 Sr 0.15 CuO 4 having zero resistance below 35 K. The crystal structure at 300K (tetragonal K 2 NiF 4 -type) was refined from X-ray powder diffraction data. The d.c. susceptibility shows no indication for the existence of localized Cu 2+ moments. The observation of a 60% Meissner effect and a smeared jump at T c in the specific-heat curve prove the intrinsic character of this superconducting state. The amplitude of this jump is compatible with the DOS estimated from the Pauli susceptibility. With a critical magnetic field slope dH c2 /dT| Tc = - 2.5 T/K, the orbital critical field is expected to be of the order of 64 T

Influence of oxygen disordering on static magnetic susceptibility of YBa2Cu3O7-x ceramics

International Nuclear Information System (INIS)

Sokolov, B.Yu.; Vil'danov, R.R.

2008-01-01

Influence of disordering of the populated oxygen positions in YBa 2 Cu 3 O 7-x ceramic's structure on its static magnetic susceptibility in the range of temperatures T>Tc is investigated. For occurrence of disordering the initial ceramics YBa 2 Cu 3 O 6,9 was annealed at T=520 C with the subsequent quenching in liquid nitrogen. Evolutions of a magnetic susceptibility and resistance of annealed ceramics during its air storage at a room temperature were studied. It is revealed that, unlike the initial optimum doped ceramics, annealed samples have appreciable temperature dependence of a magnetic susceptibility. Interpretation of results is executed on the basis of model of electronic phase separation and occurrence of a pseudo gap in a energy spectrum of free carriers of a superconductor. (authors)

T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study.

Science.gov (United States)

Roschmann, E; Wienker, T F; Gerok, W; Volk, B A

1993-12-01

Genetic susceptibility of celiac disease is primarily associated with a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully account for the genetic predisposition. Therefore, the aim of this study was to examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac disease. HLA class II typing was performed by polymerase chain reaction amplification in combination with sequence-specific oligonucleotide hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis. Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between patients with celiac disease (n = 53) and control patients (n = 67), and relative risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35 for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at TCRB, showing no significant association. Additionally, linkage analysis was performed in 23 families. The logarithm of odd scores for celiac disease vs. the TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage. These data suggest that the analyzed TCR variable gene segments V alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to celiac disease.

Methicillin-resistant Staphylococcus aureus isolates with SCCmec type V and spa types t437 or t1081 associated to discordant susceptibility results between oxacillin and cefoxitin, Central Taiwan.

Science.gov (United States)

Ho, Cheng-Mao; Lin, Chien-Yu; Ho, Mao-Wang; Lin, Hsiao-Chuan; Chen, Chao-Jung; Lin, Lee-Chung; Lu, Jang-Jih

2016-12-01

Staphylococcus aureus isolates with discordant susceptibility results between oxacillin and cefoxitin obtained using automated microbiology systems are infrequently observed. From April 2013 to December 2014, 1956 methicillin-resistant S. aureus (MRSA) and 1761 methicillin-susceptible S. aureus isolates were obtained from different patients. Forty isolates (1.1% and 2% in case of S. aureus and MRSA, respectively) with discordant susceptibility results (oxacillin susceptible and cefoxitin resistant) and carrying mecA gene were obtained. Except 2 SCCmec type IV isolates, 38 MRSA isolates were all SCCmec type V (V T or non-V T ), which were further divided into V T (n=22) and non-V T (n=16). The most common spa type in V T and non-V T isolates were t437 (n=19) and t1081 (n=13), respectively. Only 55% of patients received effective antimicrobial agents; 2 mortalities were not attributable to MRSA infection. Using standard agar dilution, 17 MRSA isolates (0.46% and 0.87% in case of S. aureus and MRSA, respectively) had oxacillin MIC in the susceptible ranges (oxacillin-susceptible MRSA [OS-MRSA]); all carried SCCmec type V (V T , n=8; non-V T , n=9). The most common spa-MLST types of OS-MRSA in V T and non-V T were t437-ST59 (n=4) and t1081-ST45 (n=7), respectively. Concomitant testing by both cefoxitin- and oxacillin-based methods is a practical strategy for OS-MRSA detection in the clinical laboratories. Continuous monitoring of OS-MRSA isolates is necessary to elucidate their impact in clinical infectious diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of multimodal segmentation based on 3D T1-, T2- and FLAIR-weighted images - the difficulty of choosing.

Science.gov (United States)

Lindig, Tobias; Kotikalapudi, Raviteja; Schweikardt, Daniel; Martin, Pascal; Bender, Friedemann; Klose, Uwe; Ernemann, Ulrike; Focke, Niels K; Bender, Benjamin

2018-04-15

Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28.1 years,19-40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49.0 years, 25-67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results. Copyright © 2017 Elsevier

NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1 x T4 and Watson-Crick T1 x A4 base pairs flanking the bisintercalation site

International Nuclear Information System (INIS)

Gao, X.; Patel, D.J.

1988-01-01

The authors report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-Tr) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets records in H 2 O and D 2 O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding the dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A large set of intermolecular contacts established from nuclear Overhauser effects (NOEs) between antibiotic and nucleic acid protons in the echinomycin-tetranucleotide complexes in solution are consistent with corresponding contacts reported for echinomycin-oligonucleotide complexes in the crystalline state. The authors demonstrate that the G x G base pairs adopt Watson-Crick pairing in both d(ACGT) and d(TCGA) complexes in solution. By contrast, the A1 x T4 base pairs adopt Hoogsteen pairing for the echinomycin-d(A1-C2-G3-Tr) complex while the T1 x A4 base pairs adopt Watson-Crick pairing for the echinomycin-d(T1-C2-G3-A4) complex in aqueous solution. These results emphasize the role of sequence in discriminating between Watson-Crick and Hoogsteen pairs at base pairs flanking the echinomycin bisintercalation site in solution

Coupled 1D-2D hydrodynamic inundation model for sewer overflow: Influence of modeling parameters

Directory of Open Access Journals (Sweden)

Adeniyi Ganiyu Adeogun

2015-10-01

Full Text Available This paper presents outcome of our investigation on the influence of modeling parameters on 1D-2D hydrodynamic inundation model for sewer overflow, developed through coupling of an existing 1D sewer network model (SWMM and 2D inundation model (BREZO. The 1D-2D hydrodynamic model was developed for the purpose of examining flood incidence due to surcharged water on overland surface. The investigation was carried out by performing sensitivity analysis on the developed model. For the sensitivity analysis, modeling parameters, such as mesh resolution Digital Elevation Model (DEM resolution and roughness were considered. The outcome of the study shows the model is sensitive to changes in these parameters. The performance of the model is significantly influenced, by the Manning's friction value, the DEM resolution and the area of the triangular mesh. Also, changes in the aforementioned modeling parameters influence the Flood characteristics, such as the inundation extent, the flow depth and the velocity across the model domain. Keywords: Inundation, DEM, Sensitivity analysis, Model coupling, Flooding

Low frequency variants in the exons only encoding isoform A of HNF1A do not contribute to susceptibility to type 2 diabetes.

Directory of Open Access Journals (Sweden)

Bahram Jafar-Mohammadi

2009-08-01

Full Text Available There is considerable interest in the hypothesis that low frequency, intermediate penetrance variants contribute to the proportion of Type 2 Diabetes (T2D susceptibility not attributable to the common variants uncovered through genome-wide association approaches. Genes previously implicated in monogenic and multifactorial forms of diabetes are obvious candidates in this respect. In this study, we focussed on exons 8-10 of the HNF1A gene since rare, penetrant mutations in these exons (which are only transcribed in selected HNF1A isoforms are associated with a later age of diagnosis of Maturity onset diabetes of the young (MODY than mutations in exons 1-7. The age of diagnosis in the subgroup of HNF1A-MODY individuals with exon 8-10 mutations overlaps with that of early multifactorial T2D, and we set out to test the hypothesis that these exons might also harbour low-frequency coding variants of intermediate penetrance that contribute to risk of multifactorial T2D.We performed targeted capillary resequencing of HNF1A exons 8-10 in 591 European T2D subjects enriched for genetic aetiology on the basis of an early age of diagnosis ( or =1 affected sibling. PCR products were sequenced and compared to the published HNF1A sequence. We identified several variants (rs735396 [IVS9-24T>C], rs1169304 [IVS8+29T>C], c.1768+44C>T [IVS9+44C>T] and rs61953349 [c.1545G>A, p.T515T] but no novel non-synonymous coding variants were detected.We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples. Nevertheless, the rationale for seeking low-frequency causal variants in genes known to contain rare, penetrant mutations remains strong and should motivate efforts to screen other genes in a similar fashion.

Vitamin D-binding protein controls T cell responses to vitamin D

DEFF Research Database (Denmark)

Kongsbak, Martin; von Essen, Marina Rode; Levring, Trine Bøegh

2014-01-01

BACKGROUND: In vitro studies have shown that the active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), can regulate differentiation of CD4+ T cells by inhibiting Th1 and Th17 cell differentiation and promoting Th2 and Treg cell differentiation. However, the serum concentration of 1...... that activated T cells express the 25(OH)D-1α-hydroxylase CYP27B1 that converts 25(OH)D3 to 1,25(OH)2D3, it is still controversial whether activated T cells have the capacity to produce sufficient amounts of 1,25(OH)2D3 to affect vitamin D-responsive genes. Furthermore, it is not known how the vitamin D......-binding protein (DBP) found in high concentrations in serum affects T cell responses to 25(OH)D3. RESULTS: We found that activated T cells express CYP27B1 and have the capacity to produce sufficient 1,25(OH)2D3 to affect vitamin D-responsive genes when cultured with physiological concentrations of 25(OH)D3...

Vitamin D Actions on CD4+ T cells in Autoimmune Disease

Directory of Open Access Journals (Sweden)

Colleen Elizabeth Hayes

2015-03-01

Full Text Available This review summarizes and integrates research on vitamin D and CD4+ T lymphocyte biology to develop new mechanistic insights into the molecular etiology of autoimmune disease. A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. Evidence for CD4+ T cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4+ T lymphocytes is summarized to support the thesis that calcitriol is sunlight’s main protective signal transducer in autoimmune disease risk. Animal modeling and human mechanistic data to support the view that vitamin D probably influences thymic negative selection, effector Th1 and Th17 pathogenesis and responsiveness to extrinsic cell death signals, FoxP3+CD4+ Treg cell and CD4+ Tr1 cell functions, and a Th1-Tr1 switch. The proposed Th1-Tr1 switch appears to bridge two stable, self-reinforcing immune states, pro- and anti-inflammatory, each with a characteristic gene regulatory network. The bi-stable switch would enable T cells to integrate signals from pathogens, hormones, cell-cell interactions, and soluble mediators and respond in a biologically appropriate manner. Finally, we highlight unanswered questions that potentially informative future research directions that may speed delivery of etiology-based strategies to reduce autoimmune disease.

Plasminogen activator inhibitor-1 4G/5G and the MTHFR 677C/T polymorphisms and susceptibility to polycystic ovary syndrome: a meta-analysis.

Science.gov (United States)

Lee, Young Ho; Song, Gwan Gyu

2014-04-01

The aim of this study was to explore whether the plasminogen activator inhibitor-1 (PAI-1) 4G/5G and the methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Meta-analyses were conducted to determine the association between the PAI-1 4G/5G and MTHFR 677C/T polymorphisms and PCOS using: (1) allele contrast (2) homozygote contrast, (3) recessive, and (4) dominant models. For meta-analysis, nine studies of the PAI-1 4G/5G polymorphism with 2384 subjects (PCOS, 1615; controls, 769) and eight studies of the MTHFR 677C/T polymorphism with 1270 study subjects were included. Meta-analysis of all study subjects showed no association between PCOS and the PAI-1 4G allele (OR=0.949, 95% CI=0.671-1.343, p=0.767). Stratification by ethnicity, however, indicated a significant association between the PAI-1 4G allele and PCOS in Turkish and Asian populations (OR=0.776, 95% CI=0.602-0.999, p=0.049; OR=1.749, 95% CI=1.297-2.359, p=2.5×10(-5) respectively). In addition, meta-analysis indicated an association between PCOS and the PAI-1 4G4G+4G5G genotype in Europeans (OR=1.406, 95% CI=1.025-1.928, p=0.035). However, meta-analysis of all study subjects showed no association between PCOS and the MTHFR 677T allele (OR=0.998, 95% CI=0.762-1.307, p=0.989), including Europeans (OR=0.806, 95% CI=0.610-1.063, p=0.126). Meta-analysis showed no association between PCOS and the MTHFR 677C/T polymorphism using homozygote contrast, and recessive and dominant models. In conclusion, meta-analysis suggests the PAI-1 4G/5G polymorphism is associated with susceptibility to PCOS in European, Turkish, and Asian populations, but the MTHFR 677C/T polymorphism is not associated with susceptibility to PCOS in Europeans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians.

Science.gov (United States)

Mustapha, Mohd Aminudin; Shahpudin, Siti Nurfatimah Mohd; Aziz, Ahmad Aizat Abdul; Ankathil, Ravindran

2012-06-07

To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk. Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher's exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software. On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003). Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.

Quantitative influence of minor and impurity elements on hot cracking susceptibility of extra high-purity type 310 stainless steel

International Nuclear Information System (INIS)

Saida, Kazuyoshi; Matsushita, Hideki; Nishimoto, Kazutoshi; Kiuchi, Kiyoshi; Nakayama, Junpei

2013-01-01

To evaluate the influence of minor and impurity elements such as C, Mn, P and S on the solidification and ductility-dip cracking susceptibilities of extra high-purity type 310 stainless steels, the transverse-Varestraint test was conducted by using several type 310 stainless steels with different amounts of C, Mn, P and S. Two types of hot cracks occurred in these steels by Varestraint test; solidification and ductility-dip cracks. The solidification cracking susceptibility was significantly reduced as the amounts of C, P and S decreased. The ductility-dip cracking susceptibility also reduced with a decrease in P and S contents. It adversely, however, increased as the C content of the steels was reduced. Mn didn't greatly affect the hot cracking susceptibility of the extra high-purity steels. The characteristic influence on solidification cracking was the ratio of P:S:C=1:1.3:0.56, while Mn negligibly ameliorated solidification cracking in the extra low S (and P) steels. The numerical analysis on the solidification brittle temperature range (BTR) revealed that the reduced solidification cracking susceptibility with decreasing the amounts of C, P and S in steel could be attributed to the reduced BTR due to the suppression of solidification segregation of minor and impurity elements in the finally solidified liquid film between dendrites. On the other hand, a molecular orbital analysis to estimate the binding strength of the grain boundary suggested that the increased ductility-dip cracking susceptibility in extra high-purity steels was caused by grain boundary embrittlement due to the refining of beneficial elements for grain boundary strengthening such as C. (author)

Influence of high magnetic field strengths and parallel acquisition strategies on image quality in cardiac 2D CINE magnetic resonance imaging: comparison of 1.5 T vs. 3.0 T

International Nuclear Information System (INIS)

Gutberlet, Matthias; Schwinge, Kerstin; Freyhardt, Patrick; Spors, Birgit; Grothoff, Matthias; Denecke, Timm; Luedemann, Lutz; Felix, Roland; Noeske, Ralph; Niendorf, Thoralf

2005-01-01

The aim of this paper is to examine signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image quality of cardiac CINE imaging at 1.5 T and 3.0 T. Twenty volunteers underwent cardiac magnetic resonance imaging (MRI) examinations using a 1.5-T and a 3.0-T scanner. Three different sets of breath-held, electrocardiogram-gated (ECG) CINE imaging techniques were employed, including: (1) unaccelerated SSFP (steady state free precession), (2) accelerated SSFP imaging and (3) gradient-echo-based myocardial tagging. Two-dimensional CINE SSFP at 3.0 T revealed an SNR improvement of 103% and a CNR increase of 19% as compared to the results obtained at 1.5 T. The SNR reduction in accelerated 2D CINE SSFP imaging was larger at 1.5 T (37%) compared to 3.0 T (26%). The mean SNR and CNR increase at 3.0 T obtained for the tagging sequence was 88% and 187%, respectively. At 3.0 T, the duration of the saturation bands persisted throughout the entire cardiac cycle. For comparison, the saturation bands were significantly diminished at 1.5 T during end-diastole. For 2D CINE SSFP imaging, no significant difference in the left ventricular volumetry and in the overall image quality was obtained. For myocardial tagging, image quality was significantly improved at 3.0 T. The SNR reduction in accelerated SSFP imaging was overcompensated by the increase in the baseline SNR at 3.0 T and did not result in any image quality degradation. For cardiac tagging techniques, 3.0 T was highly beneficial, which holds the promise to improve its diagnostic value. (orig.)

Magnetic susceptibility measurement using 2D magnetic resonance imaging

Czech Academy of Sciences Publication Activity Database

Marcon, P.; Bartušek, Karel; Burdkova, M.; Dokoupil, Zdeněk

2011-01-01

Roč. 22, č. 10 (2011), 105702:1-8 ISSN 0957-0233 R&D Projects: GA ČR GAP102/11/0318; GA MŠk ED0017/01/01 Institutional research plan: CEZ:AV0Z20650511 Keywords : magnetic flux density * magnetic susceptibility * MRI * MR signal * reaction field Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.494, year: 2011

HIV-1 transgenic rats develop T cell abnormalities

International Nuclear Information System (INIS)

Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

2004-01-01

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

Influence of fractionation and time on local control of T1 and T2 glottic carcinoma

International Nuclear Information System (INIS)

Le, Quynh-Thu; Krieg, Richard M.; Quivey, Jeanne M.; Fu, Karen K.; Meyler, Thomas S.; Stuart, Alex A.; Phillips, Theodore L.

1996-01-01

Purpose: To evaluate the influence of fraction size and overall time on local control of T1 and T2 glottic carcinoma Methods and Materials: Between 1956 and 1995, 318 consecutive patients with early glottic carcinoma (250 T1, 68 T2) were treated with definitive megavoltage radiotherapy at UCSF. Treatment was delivered using conventional fractionation at one fraction/day, 5 days/week. Minimum tumor dose ranged from 50 to 81Gy (median: 61Gy). The fraction size was 200cGy. Conclusions: Risk of tumor recurrence increased with higher T-stage, smaller fraction size, and longer overall time. Our results suggest that for optimal local control, radiotherapy for early glottic carcinoma should be completed as soon as possible, preferably within 6 weeks, using a fraction size ≥ 225cGy. Our current policy is to treat T1 and T2 vocal cord carcinomas with 225cGy/fraction/day, 5 days/week to a total dose of 63-65Gy

Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread

Science.gov (United States)

Severns, Paul M.; Estep, Laura K.; Sackett, Kathryn E.; Mundt, Christopher C.

2014-01-01

Summary Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population

Enhancement of D-T reaction rate due to D-T contact

International Nuclear Information System (INIS)

Hitoki, Shigehisa; Ogasawara, Masatada; Aono, Osamu.

1979-09-01

The reaction rate that is appropriate for magnetized nonuniform plasma is numerically calculated to investigate the enhancement of the D-T reaction rate. Spatial separation of the guiding center distributions of D and T enhances the reaction rate. Cases of several guiding center configurations are investigated. The largest enhancement is obtained, when both guiding center distributions are delta-functions which are separated by a length that corresponds to the Gamow peak energy. As compared with the case of no separation of D and T, the maximum enhancing factors obtained are 2.3 for total reaction rate and 1.6 for local reaction rate. Cases of the guiding center distributions with finite widths are also investigated. (author)

The CCL3L1-CCR5 genotype influences the development of AIDS, but not HIV susceptibility or the response to HAART

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Tanmoy [Los Alamos National Laboratory; Stanton, Jennifer [NORTHWESTERN UNIV; Kim, Eun - Young [NORTHWESTERN UNIV; Kunstman, Kevin [NORTHWESTERN UNIV; Phair, John [NORTHWESTERN UNIV; Jacobson, Lisa P [JOHNS HOPKINS UNIV; Wolinsky, Steven M [NORTHWESTERN UNIV

2008-01-01

A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes the CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).

Susceptibility to and impact of interpersonal influence in an investment context

NARCIS (Netherlands)

Hoffmann, A. O. I.; Broekhuizen, T. L. J.

2009-01-01

This paper demonstrates the relevance of consumers' susceptibility to interpersonal influence (CSII) in an investment context. In Study 1, a survey of individual investors, investment-related knowledge, psycho-social risks, and social needs emerge as antecedents that explain investors'

Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes.

OpenAIRE

Taylor, G.M.; Gokhale, D.A.; Crowther, D.; Woll, P.J.; Harris, M.; Ryder, D.; Ayres, M.; Radford, J.A.

1999-01-01

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS)...

High spatial resolution 3D MR cholangiography with high sampling efficiency technique (SPACE): Comparison of 3 T vs. 1.5 T

Energy Technology Data Exchange (ETDEWEB)

Arizono, Shigeki [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: arizono@kuhp.kyoto-u.ac.jp; Isoda, Hiroyoshi [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: sayuki@kuhp.kyoto-u.ac.jp; Maetani, Yoji S. [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: mbo@kuhp.kyoto-u.ac.jp; Hirokawa, Yuusuke [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: yuusuke@kuhp.kyoto-u.ac.jp; Shimada, Kotaro [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: kotaro@kuhp.kyoto-u.ac.jp; Nakamoto, Yuji [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ynakamo1@kuhp.kyoto-u.ac.jp; Shibata, Toshiya [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ksj@kuhp.kyoto-u.ac.jp; Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ktogashi@kuhp.kyoto-u.ac.jp

2010-01-15

Purpose: The aim of this study was to evaluate image quality of 3D MR cholangiography (MRC) using high sampling efficiency technique (SPACE) at 3 T compared with 1.5 T. Methods and materials: An IRB approved prospective study was performed with 17 healthy volunteers using both 3 and 1.5 T MR scanners. MRC images were obtained with free-breathing navigator-triggered 3D T2-weighted turbo spin-echo sequence with SPACE (TR, >2700 ms; TE, 780 ms at 3 T and 801 ms at 1.5 T; echo-train length, 121; voxel size, 1.1 mm x 1.0 mm x 0.84 mm). The common bile duct (CBD) to liver contrast-to-noise ratios (CNRs) were compared between 3 and 1.5 T. A five-point scale was used to compare overall image quality and visualization of the third branches of bile duct (B2, B6, and B8). The depiction of cystic duct insertion and the highest order of bile duct visible were also compared. The results were compared using the Wilcoxon signed-ranks test. Results: CNR between the CBD and liver was significantly higher at 3 T than 1.5 T (p = 0.0006). MRC at 3 T showed a significantly higher overall image quality (p = 0.0215) and clearer visualization of B2 (p = 0.0183) and B6 (p = 0.0106) than at 1.5 T. In all analyses of duct visibility, 3 T showed higher scores than 1.5 T. Conclusion: 3 T MRC using SPACE offered better image quality than 1.5 T. SPACE technique facilitated high-resolution 3D MRC with excellent image quality at 3 T.

Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

Science.gov (United States)

Ichikawa, Hitomi; Sugimoto, Mitsushige; Uotani, Takahiro; Sahara, Shu; Yamade, Mihoko; Iwaizumi, Moriya; Yamada, Takanori; Osawa, Satoshi; Sugimoto, Ken; Miyajima, Hiroaki; Yamaoka, Yoshio; Furuta, Takahisa

2015-04-01

Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer. © 2014 John Wiley & Sons Ltd.

Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

Science.gov (United States)

Lipner, Ettie M.; Garcia, Benjamin J.; Strong, Michael

2016-01-01

Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects. PMID:26751573

Entitlement Can Both Decrease and Increase Consumer Susceptibility to Social Influence

NARCIS (Netherlands)

van der Heide, Martine; Fennis, Bob; van Ittersum, Koert; Trampe, Debra; Diehl, Kristin; Yoon, Carolyn

2015-01-01

Two studies indicate that entitlement—a sense that one deserves special treatment and is exempt from normal social demands—can both buffer and boost consumers’ proneness to social influence. Specifically, Study 1 shows that entitlement reduces susceptibility to consistency appeals. Study 2, however,

Genetic polymorphisms of surfactant protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers.

Science.gov (United States)

Issac, Marianne Samir M; Ashur, Wafaa; Mousa, Heba

2014-06-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level. A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry. Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75 % predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p = 0.013). FEF25-75 % predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [p = 0

Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p

DEFF Research Database (Denmark)

Moreira, José Manuel Alfonso; Remacle, J E; Kielland-Brandt, Morten

1998-01-01

A cis-acting element required for GCN4-independent basal-level transcription of ILV1 was previously identified in our laboratories as a binding site for the REB1 protein (Reb1p). Further deletion analysis of the ILV1 promoter region identified a second element also required for GCN4-independent...... basal-level ILV1 expression. This second element is an A.T-rich tract (26 As out of 32 nucleotides) situated 15 bp downstream of the Reb1p-binding site. Deletion of both the Reblp site and the poly(dA:dT) element totally eliminates basal activity of the ILV1 promoter. We show that the two elements act...... synergistically to control ILV1 expression and that the synergistic effect is distance dependent. We demonstrate that (i) datin (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans-activating factor in the ILV1...

TFTR D-T results

International Nuclear Information System (INIS)

Meade, D.M.

1994-01-01

Temperatures, densities and confinement of deuterium plasmas confined in tokamaks have been achieved within the last decade that are approaching those required for a D-T reactor. As a result, the unique phenomena present in a D-T reactor plasma (D-T plasma confinement, alpha confinement, alpha heating and possible alpha driven instabilities) can now be studied in the laboratory. Recent experiments on the Tokamak Fusion Test Reactor (TFTR) have been the first magnetic fusion experiments to study plasmas with reactor fuel concentrations of tritium. The injection of ∼ 20 MW of tritium and 14 MW of deuterium neutral beams into the TFTR produced a plasma with a T/D density ratio of ∼1 and yielded a maximum fusion power of ∼ 9.2 MW. The fusion power density in the core of the plasma was ∼ 1.8 MW m -3 approximating that expected in a D-T fusion reactor. A TFTR plasma with T/D density ratio of ∼ 1 was found to have ∼ 20% higher energy confinement time than a comparable D plasma, indicating a confinement scaling with average ion mass, A, of τ E ∼ A 0.6 . The core ion temperature increased from 30 keV to 37 keV due to a 35% improvement of ion thermal conductivity. Using the electron thermal conductivity from a comparable deuterium plasma, about 50% of the electron temperature increase from 9 keV to 10.6 keV can be attributed to electron heating by the alpha particles. The ∼ 5% loss of alpha particles, as observed on detectors near the bottom edge of the plasma, was consistent with classical first orbit loss without anomalous effects. Initial measurements have been made of the confined energetic alphas and the resultant alpha ash density. At fusion power levels of 7.5 MW, fluctuations at the Toroidal Alfven Eigenmode frequency were observed by the fluctuation diagnostics. However, no additional alpha loss due to the fluctuations was observed

Morphological imaging and T2 and T2* mapping of hip cartilage at 7 Tesla MRI under the influence of intravenous gadolinium

International Nuclear Information System (INIS)

Lazik-Palm, Andrea; Geis, Christina; Goebel, Juliane; Theysohn, Jens M.; Kraff, Oliver; Johst, Soeren; Ladd, Mark E.; Quick, Harald H.

2016-01-01

To investigate the influence of intravenous gadolinium on cartilage T2 and T2* relaxation times and on morphological image quality at 7-T hip MRI. Hips of 11 healthy volunteers were examined at 7 T. Multi-echo sequences for T2 and T2* mapping, 3D T1 volumetric interpolated breath-hold examination (VIBE) and double-echo steady-state (DESS) sequences were acquired before and after intravenous application of gadolinium according to a delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol. Cartilage relaxation times were measured in both scans. Morphological sequences were assessed quantitatively using contrast ratios and qualitatively using a 4-point Likert scale. Student's t-test, Pearson's correlation (ρ) and Wilcoxon sign-rank test were used for statistical comparisons. Pre- and post-contrast T2 and T2* values were highly correlated (T2: acetabular: ρ = 0.76, femoral: ρ = 0.77; T2*: acetabular: ρ = 0.80, femoral: ρ = 0.72). Gadolinium enhanced contrasts between cartilage and joint fluid in DESS and T1 VIBE according to the qualitative (p = 0.01) and quantitative (p < 0.001) analysis. The delineation of acetabular and femoral cartilage and the labrum predominantly improved with gadolinium. Gadolinium showed no relevant influence on T2 or T2* relaxation times and improved morphological image quality at 7 T. Therefore, morphological and quantitative sequences including dGEMRIC can be conducted in a one-stop-shop examination. (orig.)

Morphological imaging and T2 and T2* mapping of hip cartilage at 7 Tesla MRI under the influence of intravenous gadolinium

Energy Technology Data Exchange (ETDEWEB)

Lazik-Palm, Andrea; Geis, Christina; Goebel, Juliane; Theysohn, Jens M. [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kraff, Oliver; Johst, Soeren [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Ladd, Mark E. [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High-Field and Hybrid MR Imaging, Essen (Germany)

2016-11-15

To investigate the influence of intravenous gadolinium on cartilage T2 and T2* relaxation times and on morphological image quality at 7-T hip MRI. Hips of 11 healthy volunteers were examined at 7 T. Multi-echo sequences for T2 and T2* mapping, 3D T1 volumetric interpolated breath-hold examination (VIBE) and double-echo steady-state (DESS) sequences were acquired before and after intravenous application of gadolinium according to a delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol. Cartilage relaxation times were measured in both scans. Morphological sequences were assessed quantitatively using contrast ratios and qualitatively using a 4-point Likert scale. Student's t-test, Pearson's correlation (ρ) and Wilcoxon sign-rank test were used for statistical comparisons. Pre- and post-contrast T2 and T2* values were highly correlated (T2: acetabular: ρ = 0.76, femoral: ρ = 0.77; T2*: acetabular: ρ = 0.80, femoral: ρ = 0.72). Gadolinium enhanced contrasts between cartilage and joint fluid in DESS and T1 VIBE according to the qualitative (p = 0.01) and quantitative (p < 0.001) analysis. The delineation of acetabular and femoral cartilage and the labrum predominantly improved with gadolinium. Gadolinium showed no relevant influence on T2 or T2* relaxation times and improved morphological image quality at 7 T. Therefore, morphological and quantitative sequences including dGEMRIC can be conducted in a one-stop-shop examination. (orig.)

[TNF-α, diabetes type 1 and regulatory T cells].

Science.gov (United States)

Ryba, Monika; Myśliwska, Jolanta

2010-01-01

Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

Search of type 2 diabetes susceptibility gene on chromosome 20q

International Nuclear Information System (INIS)

Takeuchi, F.; Yanai, K.; Inomata, H.; Kuzuya, N.; Kajio, H.; Honjo, S.; Takeda, N.; Kaburagi, Y.; Yasuda, K.; Shirasawa, S.; Sasazuki, T.; Kato, N.

2007-01-01

Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4α (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30-2.31) (P 0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study

Polymorphisms -1082 G/A and -819 C/T in the interleukin-10 gene are not associated with gout susceptibility in the Chinese Han male population.

Science.gov (United States)

Liu, Shiguo; Zhang, Kun; Yin, Congcong; Han, Lin; Sun, Yuping; Ren, Wei; Chu, Nan; Li, Changgui

2012-08-01

Gout is caused by monosodium urate crystal-induced inflammation of the joints and periarticular tissues. Interleukin 10 (IL-10) is an important immunoregulatory cytokine, levels of which can be influenced by functional single-nucleotide polymorphisms in the promoter. To investigate the association of -1082 G/A and -819 C/T polymorphisms in the IL-10 promoter with gout susceptibility in the Chinese Han male population. A case-control study was performed in 302 patients and 284 controls. Genotyping of IL-10 -1082 G/A and -819 C/T polymorphisms was performed by DNA sequencing techniques. An association analysis was analyzed by the χ(2) test. No significant differences were found in -819T/C and -1082 A/G genotypic and allelic frequencies between gout cases and controls (for -819T/C, χ(2)=0.212, df=1, p=0.645 by genotype; χ(2)=0.079, df=1, p=0.779 by allele; for -1082 A/G, χ(2)=2.116, df=1, p=0.146 by genotype; χ(2)=1.854, df=1, p=0.173 by allele). IL-10 -1082 G/A and -819 C/T polymorphisms may not be associated with susceptibility to gout and thus do not play a major role in the development of gout in the Chinese Han male population.

Variable flip angle 3D ultrashort echo time (UTE) T1 mapping of mouse lung: A repeatability assessment.

Science.gov (United States)

Alamidi, Daniel F; Smailagic, Amir; Bidar, Abdel W; Parker, Nicole S; Olsson, Marita; Hockings, Paul D; Lagerstrand, Kerstin M; Olsson, Lars E

2018-03-08

Lung T 1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T 1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. To evaluate the feasibility of regional lung T 1 quantification with VFA 3D-UTE and to investigate long- and short-term T 1 repeatability in the lungs of naive mice. Prospective preclinical animal study. Eight naive mice and phantoms. 3D free-breathing radial UTE (8 μs) at 4.7T. VFA 3D-UTE T 1 calculations were validated against T 1 values measured with inversion recovery (IR) in phantoms. Lung T 1 and proton density (S 0 ) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T 1 measurements were performed during one of the imaging sessions. Agreement in T 1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson 's correlation analysis. The T 1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Good T 1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T 1 in lung and muscle showed a 5% and 3% CV (1255 ± 63 msec and 1432 ± 42 msec, respectively, mean ± SD) with no changes in T 1 or S 0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T 1 and S 0 . VFA 3D-UTE shows promise as a reliable T 1 mapping method that enables full lung coverage, high signal-to-noise ratio (∼25), and spatial resolution (300 μm) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Acute myocardial infarction: susceptibility-weighted cardiac MRI for the detection of reperfusion haemorrhage at 1.5 T

International Nuclear Information System (INIS)

Durighel, G.; Tokarczuk, P.F.; Karsa, A.; Gordon, F.; Cook, S.A.; O'Regan, D.P.

2016-01-01

Aim: To assess whether susceptibility-weighted imaging (SWI) provides better image contrast for the detection of haemorrhagic ischaemia–reperfusion injury in the heart. Materials and methods: Thirty patients (all men; mean age 53 years) underwent cardiac magnetic resonance imaging (MRI) within 7 days of primary percutaneous intervention for acute ST elevation myocardial infarction (STEMI). Multiple gradient-echo T2* sequences with magnitude and phase reconstructions were acquired. A high-pass filtered phase map was used to create a mask for the SWI reconstructions. The difference in image contrast was assessed in those patients with microvascular obstruction. A mixed effects regression model was used to test the effect of echo time and reconstruction method on phase and contrast-to-noise ratio (CNR). Medians and interquartile ranges (IQR) are reported. Results: T2* in haemorrhagic infarcts was shorter than in non-haemorrhagic infarcts (33.5 ms [24.9–43] versus 49.9 ms [44.6–67.6]; p=0.0007). The effect of echo time on phase was significant (p<0.0001), as was the effect of haemorrhage on phase (p=0.0016). SWI reconstruction had a significant effect on the CNR at all echo times (echoes 1–5, p<0.0001; echo 6, p=0.01; echo 7, p=0.02). The median echo number at which haemorrhage was first visible was less for SWI compared to source images (echo 2 versus echo 5, p=0.0002). Conclusion: Cardiac SWI improves the contrast between myocardial haemorrhage and the surrounding tissue following STEMI and has potential as a new tool for identifying patients with ischaemia–reperfusion injury. - Highlights: • Cardiac susceptibility-weighted imaging (SWI) is feasible at 1.5T. • Combining phase and modulus data allows blood products to be seen at shorter echo times. • This sequence improves visualisation of reperfusion myocardial haemorrhage.

Polymorphism in ficolin-1 (FCN1) gene is associated with an earlier ...

Indian Academy of Sciences (India)

diabetes mellitus (T1D) patients with celiac disease (CD) ... associated with T1D lower susceptibility. This is the first ... plasma. FCN2 is expressed in liver cells and ficolin-2 protein ... diagnosed with T1D and 193 healthy individuals (median.

Characterizing diabetes burnout in parents of youth with type 1 diabetes (T1D)

Science.gov (United States)

Managing type 1 diabetes (T1D) is complex and requires round-the-clock attention, much of which falls to parents. Parental stress and family conflict about diabetes are associated with suboptimal youth self-management and glycemic outcomes, yet little research has described parents' experiences with...

A functional polymorphism C-509T in TGFβ-1 promoter contributes to susceptibility and prognosis of lone atrial fibrillation in Chinese population.

Directory of Open Access Journals (Sweden)

Hailong Cao

Full Text Available Transforming growth factor-β1 (TGF-β1 is an important mediator of atrial fibrosis and atrial fibrillation (AF. But the involved genetic mechanism is unknown. Herein, the TGF-β1 C-509 T polymorphism (rs1800469 was genotyped in a case-control study of 840 patients and 845 controls in Chinese population to explore the association between the polymorphism and susceptibility and prognosis of lone AF. As a result, the CT and/or TT genotypes had an increased lone AF risk [adjusted odds ratio (OR = 1.50 for CT, OR = 3.72 for TT, and OR = 2.15 for CT/TT], compared with the TGF-β1CC genotype. Moreover, patients carrying CT/TT genotypes showed a higher possibility of AF recurrence after catheter ablation, compared with patients carrying CC genotype. In a genotype-phenotype correlation analysis using 24 normal left atrial appendage samples, increasing gradients of atrial TGF-β1 expression levels positively correlated with atrial collagen volume fraction were identified in samples with CC, CT and TT genotypes. The in vitro luciferase assays also showed a higher luciferase activity of the -509 T allele than that of the -509 C allele. In conclusion, the TGF-β1 C-509 T polymorphism is involved in the etiology of lone AF and thus may be a marker for genetic susceptibility to lone AF and predicting prognosis after catheter ablation in Chinese populations. Therefore, we provide new information about treatment strategies and our understanding of TGF-β1 in AF.

Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry.

Science.gov (United States)

Clements, Mark A; Foster, Nicole C; Maahs, David M; Schatz, Desmond A; Olson, Beth A; Tsalikian, Eva; Lee, Joyce M; Burt-Solorzano, Christine M; Tamborlane, William V; Chen, Vincent; Miller, Kellee M; Beck, Roy W

2016-08-01

Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes. Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p HbA1c trajectory. Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The common mouse protozoa Tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility.

Science.gov (United States)

Escalante, Nichole K; Lemire, Paul; Cruz Tleugabulova, Mayra; Prescott, David; Mortha, Arthur; Streutker, Catherine J; Girardin, Stephen E; Philpott, Dana J; Mallevaey, Thierry

2016-12-12

The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1 -/- mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research. © 2016 Escalante et al.

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.

Brief report: personality correlates of susceptibility to peer influence in adolescence.

Science.gov (United States)

Stautz, Kaidy; Cooper, Andrew

2014-06-01

Adolescents show a heightened susceptibility to peer influence compared to adults. Individual differences in this susceptibility exist, yet there has been little effort to link these with broader personality processes. Reward sensitivity and impulsive behaviour are also heightened in adolescence and could affect the tendency to be influenced by peers. This study examined associations between self-reported resistance to peer influence, facets of reward sensitivity and impulsivity, and subjective social status in a sample of 269 British sixth form students (mean age 16.79). Multiple regression analyses showed that negative and positive urgency were significantly negatively associated with resistance to peer influence. The relationship between negative urgency and resistance was moderated by subjective social status, such that individuals reporting low status showed a stronger negative relationship. Results suggest that a susceptibility to peer influence is linked with a tendency to act impulsively when in heightened emotional states. Adolescents high in negative urgency who feel lower in their social hierarchy may be particularly vulnerable. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Dynamic susceptibility of a free electron gas in a D dimensions and its analytic properties

International Nuclear Information System (INIS)

Holas, A.

1990-01-01

Properties of the free electron susceptibility as a complex function of a wave vector k and a complex frequency ω are examined. Dimensionality D of the space plays a role of a parameter, which may assume noninteger values also. While for general D the susceptibility is obtained in terms of hypergeometric functions, for integer D it can be reduced to a combination of elementary functions. A singular behavior at the points of non-analyticity ω = k modul 1±k/2 is investigated; with increasing D the singularity becomes weaker. A continued fraction representation is obtained and approximations to the susceptibility, based on it, are proposed. The Hartree-Fock static structure factor is obtained as a function of both k and D. An important for applications problem of frequency integration of the dynamic structure factor of interacting-particle systems is investigated. Explicit expressions for integration along the imaginary axis, ready for numerical work, are obtained for D = 3 and 2. (author). 20 refs

Quantitative susceptibility mapping of human brain at 3T: a multisite reproducibility study.

Science.gov (United States)

Lin, P-Y; Chao, T-C; Wu, M-L

2015-03-01

Quantitative susceptibility mapping of the human brain has demonstrated strong potential in examining iron deposition, which may help in investigating possible brain pathology. This study assesses the reproducibility of quantitative susceptibility mapping across different imaging sites. In this study, the susceptibility values of 5 regions of interest in the human brain were measured on 9 healthy subjects following calibration by using phantom experiments. Each of the subjects was imaged 5 times on 1 scanner with the same procedure repeated on 3 different 3T systems so that both within-site and cross-site quantitative susceptibility mapping precision levels could be assessed. Two quantitative susceptibility mapping algorithms, similar in principle, one by using iterative regularization (iterative quantitative susceptibility mapping) and the other with analytic optimal solutions (deterministic quantitative susceptibility mapping), were implemented, and their performances were compared. Results show that while deterministic quantitative susceptibility mapping had nearly 700 times faster computation speed, residual streaking artifacts seem to be more prominent compared with iterative quantitative susceptibility mapping. With quantitative susceptibility mapping, the putamen, globus pallidus, and caudate nucleus showed smaller imprecision on the order of 0.005 ppm, whereas the red nucleus and substantia nigra, closer to the skull base, had a somewhat larger imprecision of approximately 0.01 ppm. Cross-site errors were not significantly larger than within-site errors. Possible sources of estimation errors are discussed. The reproducibility of quantitative susceptibility mapping in the human brain in vivo is regionally dependent, and the precision levels achieved with quantitative susceptibility mapping should allow longitudinal and multisite studies such as aging-related changes in brain tissue magnetic susceptibility. © 2015 by American Journal of Neuroradiology.

Influence of dietary components on regulatory T cells

DEFF Research Database (Denmark)

Navikas, Shohreh; Teimer, Roman; Bockermann, Robert

2011-01-01

It is no longer a myth that a balanced diet is fundamental for general health. Common dietary components including vitamins A and D, omega-3 and probiotics are now widely accepted to be essential to protect against many diseases with an inflammatory nature. On the other hand, high fat diets...... components on diseases in which Tregs play a seminal role will be discussed. Among chronic diseases where dietary factors could have a direct influence via modulation of Tregs homeostasis and functions, we will review chronic tissue-specific autoimmune and inflammatory conditions such as IBD, T1D, MS, RA...

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

Science.gov (United States)

Migita, Kiyoshi; Nakamura, Minoru; Abiru, Seigo; Jiuchi, Yuka; Nagaoka, Shinya; Komori, Atsumasa; Hashimoto, Satoru; Bekki, Shigemune; Yamasaki, Kazumi; Komatsu, Tatsuji; Shimada, Masaaki; Kouno, Hiroshi; Hijioka, Taizo; Kohjima, Motoyuki; Nakamuta, Makoto; Kato, Michio; Yoshizawa, Kaname; Ohta, Hajime; Nakamura, Yoko; Takezaki, Eiichi; Nishimura, Hideo; Sato, Takeaki; Ario, Keisuke; Hirashima, Noboru; Oohara, Yukio; Naganuma, Atsushi; Muro, Toyokichi; Sakai, Hironori; Mita, Eiji; Sugi, Kazuhiro; Yamashita, Haruhiro; Makita, Fujio; Yatsuhashi, Hiroshi; Ishibashi, Hiromi; Yasunami, Michio

2013-01-01

Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study. Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies). This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.

Science.gov (United States)

Sun, Rui; Liu, Jian-Ping; Gao, Chang; Xiong, Ying-Ying; Li, Min; Wang, Ya-Ping; Su, Yan-Wei; Lin, Mei; Jiang, An-Li; Xiong, Ling-Fan; Xie, Yan; Feng, Jue-Ping

2016-05-17

Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (pCRC was observed in TC or TC/CC than CC individuals (pCRC risk was observed in AG, GG, and AG/GG than AA individuals (pCRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

Celiac Disease Does Not Influence Fracture Risk in Young Patients with Type 1 Diabetes

Science.gov (United States)

Reilly, Norelle R; Lebwohl, Benjamin; Mollazadegan, Kaziwe; Michaëlsson, Karl; Green, Peter HR; Ludvigsson, Jonas F

2015-01-01

Objectives To examine the risk of any fractures in patients with both type 1 diabetes (T1D) and celiac disease (CD) vs patients with T1D only. Study design We performed a population-based cohort study. We defined T1D as individuals aged ≤30 years who had a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964–2009. Individuals with CD were identified through biopsy report data between 1969–2008 from any of Sweden’s 28 pathology departments. Some 958 individuals had both T1D and CD and were matched for sex, age and calendar period with 4,598 reference individuals with T1D only. We then used a stratified Cox regression analysis, where CD was modeled as a time-dependent covariate, to estimate the risk of any fractures and osteoporotic fractures (hip, distal forearm, thoracic and lumbar spine, and proximal humerus) in patients with both T1D and CD compared with that in patients with T1D only. Results During follow-up, 12 patients with T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (adjusted Hazard Ratio=0.77; 95%CI=0.42–1.41) or osteoporotic fractures (adjusted Hazard Ratio=0.46; 95%CI=0.06–3.51) in patients with T1D. Stratification for time since CD diagnosis did not affect risk estimates. Conclusion Having a diagnosis of CD does not seem to influence fracture risk in young patients with T1D. Follow-up in this study was, however, too short to ascertain osteoporotic fractures which traditionally occur in old age. PMID:26589343

Genetic susceptibility to Grave's disease.

Science.gov (United States)

Li, Hong; Chen, Qiuying

2013-06-01

The variety of clinical presentations of eye changes in patients with Graves' disease (GD) suggests that complex interactions between genetic, environmental, endogenous and local factors influence the severity of Graves' ophthalmopathy (GO). It is thought that the development of GO might be influenced by genetic factors and environmental factors, such as cigarette smoking. At present, however, the role of genetic factors in the development of GO is not known. On the basis of studies with candidate genes and other genetic approaches, several susceptibility loci in GO have been proposed, including immunological genes, human leukocyte antigen (HLA), cytotoxic T-lymphocyte antigen-4 (CTLA-4), regulatory T-cell genes and thyroid-specific genes. This review gives a brief overview of the current range of major susceptibility genes found for GD.

The G1/S Specific Cyclin D2 Is a Regulator of HIV-1 Restriction in Non-proliferating Cells

Science.gov (United States)

Badia, Roger; Pujantell, Maria; Riveira-Muñoz, Eva; Puig, Teresa; Torres-Torronteras, Javier; Martí, Ramón; Clotet, Bonaventura; Ampudia, Rosa M.; Ballana, Ester

2016-01-01

Macrophages are a heterogeneous cell population strongly influenced by differentiation stimuli that become susceptible to HIV-1 infection after inactivation of the restriction factor SAMHD1 by cyclin-dependent kinases (CDK). Here, we have used primary human monocyte-derived macrophages differentiated through different stimuli to evaluate macrophage heterogeneity on cell activation and proliferation and susceptibility to HIV-1 infection. Stimulation of monocytes with GM-CSF induces a non-proliferating macrophage population highly restrictive to HIV-1 infection, characterized by the upregulation of the G1/S-specific cyclin D2, known to control early steps of cell cycle progression. Knockdown of cyclin D2, enhances HIV-1 replication in GM-CSF macrophages through inactivation of SAMHD1 restriction factor by phosphorylation. Co-immunoprecipitation experiments show that cyclin D2 forms a complex with CDK4 and p21, a factor known to restrict HIV-1 replication by affecting the function of the downstream cascade that leads to SAMHD1 deactivation. Thus, we demonstrate that cyclin D2 acts as regulator of cell cycle proteins affecting SAMHD1-mediated HIV-1 restriction in non-proliferating macrophages. PMID:27541004

CAT-D-T tokamaks

International Nuclear Information System (INIS)

Greenspan, E.; Blue, T.; Miley, G.H.

1981-01-01

The domains of plasma fuel cycles bounded by the D-T and Cat-D, and by the D-T and SCD modes of operation are examined. These domains, referred to as, respectively, the Cat-D-T and SCD-T modes of operation, are characterized by the number (γ) of tritons per fusion neutron available from external (to the plasma) sources. Two external tritium sources are considered - the blankets of the Cat-D-T (SCD-T) reactors and fission reactors supported by the Cat-D-T (SCD-T) driven hybrid reactors. It is found that by using 6 Li for the active material of the control elements of the fission reactors, it is possible to achieve γ values close to unity. Cat-D-T tokamaks could be designed to have smaller size, higher power density, lower magnetic field and even lower plasma temperature than Cat-D tokamaks; the difference becomes significant for γ greater than or equal to .75. The SCD-T mode of operation appears to be even more attractive. Promising applications identified for these Cat-D-T and SCD-T modes of operation include hybrid reactors, fusion synfuel factories and fusion reactors which have difficulty in providing all their tritium needs

Audio zesilovač 2.1 ve třídě D pro laboratorní výuku

OpenAIRE

Kolečková, Klára

2016-01-01

Práce se zabývá návrhem zapojení a konstrukcí audio zesilovače ve třídě D s pulsně šířkovou modulací. Výsledné zapojení je tvořeno ochranou napájení, aktivní výhybkou a samotným koncovým zesilovacím stupněm. Zesilovač je vytvořen v konfiguraci 2.1, středovýškový zesilovač má výstupní výkon 2 × 30 W na zátěži 8 , subwoofer 1 × 100 W na zátěži 2 . Řídicím centrem celého zapojení je integrovaný obvod TPA3116D2 od firmy Texas Instruments. Výsledný audio zesilovač bude využit jako přípravek pro la...

Influence of deformation on SCC susceptibility of austenitic stainless steel in PWR primary water

Energy Technology Data Exchange (ETDEWEB)

Kaneshima, Yoshiari; Totsuka, Nobuo; Nakajima, Nobuo [Institute of Nuclear Safety System Inc., Mihama, Fukui (Japan)

2001-09-01

Slow strain rate tests (SSRT) were carried out to evaluate the SCC susceptibility of four types of austenitic stainless steels (SUS304, SUS316, SUS304L and SUS316L) in PWR primary water. The influence of deformation on SCC susceptibility of SUS316 was studied. All types of stainless steel were susceptible to SCC, and the SCC susceptibility varied depending on the steel type. The comparison of the SSRT results and tensile test in air based on the reduction of area measurement showed that the SCC susceptibility increased with increasing the degree of deformation. For explaining the influence of deformation on SCC susceptibility, it is necessary to evaluate both intergranular and transgranular fractures. (author)

1α,25(OH2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness.

Directory of Open Access Journals (Sweden)

Nitish Boodhoo

Full Text Available 1,25-Dihydroxyvitamin D3 (Vitamin D is a naturally synthesized fat soluble vitamin shown to have immunomodulatory, anti-inflammatory and cancer prevention properties in human and murine models. Here, we studied the effects of Vitamin D on the functional abilities of avian T lymphocytes using chicken Interferon (IFN-γ ELISPOT assay, BrdU proliferation assay, Annexin V apoptosis assay and PhosFlow for detecting phosphorylated signalling molecules. The results demonstrate that Vitamin D significantly inhibited the abilities of T lymphocytes to produce IFN-γ and proliferate in vitro (P≤0.05, but retained their ability to undergo degranulation, which is a maker for cytotoxicity of these cells. Similarly, Vitamin D did not inhibit Extracellular signal-Regulated Kinase (ERK 1/2 phosphorylation, a key mediator in T cell signalling, in the stimulated T lymphocytes population, while reduced ERK1/2 phosphorylation levels in the unstimulated cells. Our data provide evidence that Vitamin D has immuno-modulatory properties on chicken T lymphocytes without inducing unresponsiveness and by limiting immuno-pathology can promote protective immunity against infectious diseases of poultry.

The immunoregulatory role of CD1d-restricted natural killer T cells in disease.

NARCIS (Netherlands)

Vliet, van der HJ; Molling, J.W.; Blomberg - van der Flier, von B.M.E.; Nishi, N.; Kolgen, W; Eertwegh, van den A.J.M.; Pinedo, H.M.; Giaccone, G.; Scheper, R.J.

2004-01-01

Natural killer T (NKT) cells constitute a T cell subpopulation that shares several characteristics with NK cells. NKT cells are characterized by a narrow T cell antigen receptor (TCR) repertoire, recognize glycolipid antigen in the context of the monomorphic CD1d antigen-presenting molecule, and

1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

Directory of Open Access Journals (Sweden)

Jae-Hoon Chang

Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells.

Science.gov (United States)

Luoma, Adrienne M; Castro, Caitlin D; Mayassi, Toufic; Bembinster, Leslie A; Bai, Li; Picard, Damien; Anderson, Brian; Scharf, Louise; Kung, Jennifer E; Sibener, Leah V; Savage, Paul B; Jabri, Bana; Bendelac, Albert; Adams, Erin J

2013-12-12

The nature of the antigens recognized by γδ T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vδ1 TCR-expressing γδ T cells, the major γδ lymphocyte population in epithelial tissues. We crystallized a Vδ1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vδ1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3δ residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vδ1+ γδ T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by γδ T cells and reveal the prevalence of lipid recognition by innate-like T cell populations. Copyright © 2013 Elsevier Inc. All rights reserved.

μ CF Study of D/T and H/D/T Mixtures in Homogeneous and Inhomogeneous Medium, and Comparison of Their Fusion Yields

Science.gov (United States)

Eskandari, M. R.; Faghihi, F.; Gheisari, R.

Muon reactivation coefficient are determined for muonic He (He = 42He = α , He = 23 He = h) for up to six (n = 1, 2, 3, ..., 6) states of formation and at temperature Tp = 100 eV and for various relative ion densities. In the next decade it may be possible to explore new conditions for further energy gain in muon catalyzed fusion system, μ CF, using nonuniform (temperature and density) plasma states. Here, we have considered a model for inhomogeneous μ CF for mixtures of D/T and H/D/T. Using coupled dynamical equations it is shown that the neutrons yield per muon injection, Yn (neutrons/muon), in the dt branch of an inhomogeneous H/D/T mixture is at least 2.24 times higher than similar homogeneous systems and this rate for a D/T mixture is 1.92. Also, we have compared the neutron yield in the dt branch of homogeneous D/T and H/D/T mixtures (temperature range T = 300-800 K, and density φ = 1 LHD). It is shown that Yn(D/T)/Yn(H/D/T) = 1.32, which is in good agreement with recently measured experimental values. In other words our calculations show that the addition of protonium to a D/T mixture leads to a significant decrease in the cycling rate for the physical conditions described herein.

Human CD1d-Restricted Natural Killer T (NKT) Cell Cytotoxicity Against Myeloid Cells

National Research Council Canada - National Science Library

Chen, Xiuxu; Gumperz, Jenny E

2006-01-01

CD1d-restricted natural killer T cells (NKT cells) are a unique subpopulation of T lymphocytes that have been shown to be able to promote potent anti-tumor responses in a number of different murine (mouse...

Association of STAT4 polymorphisms with susceptibility to type-1 autoimmune hepatitis in the Japanese population.

Directory of Open Access Journals (Sweden)

Kiyoshi Migita

Full Text Available BACKGROUND/AIMS: Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO AIH multicenter cohort study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694. The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23-2.11; P = 0.001, and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13-1.99; P = 0.005. Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44 or without liver cirrhosis (n = 186 demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies. CONCLUSIONS/SIGNIFICANCE: This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.

Poly(dA-dT).poly(dA-dT) two-pathway proton exchange mechanism. Effect of general and specific base catalysis on deuteration rates

International Nuclear Information System (INIS)

Hartmann, B.; Leng, M.; Ramstein, J.

1986-01-01

The deuteration rates of the poly(dA-dT).poly(dA-dT) amino and imino protons have been measured with stopped-flow spectrophotometry as a function of general and specific base catalyst concentration. Two proton exchange classes are found with time constants differing by a factor of 10 (4 and 0.4 s-1). The slower class represents the exchange of the adenine amino protons whereas the proton of the faster class has been assigned to the thymine imino proton. The exchange rates of these two classes of protons are independent of general and specific base catalyst concentration. This very characteristic behavior demonstrates that in our experimental conditions the exchange rates of the imino and amino protons in poly(dA-dT).poly(dA-dT) are limited by two different conformational fluctuations. We present a three-state exchange mechanism accounting for our experimental results

Influence of lipid rafts on CD1d presentation by dendritic cells

DEFF Research Database (Denmark)

Peng, Wei; Martaresche, Cecile; Escande-Beillard, Nathalie

2011-01-01

corresponding to lipid rafts and we describe that alpha-GalCer enhanced CD1d amount in the low density detergent insoluble fraction. We conclude that the membrane environment of CD1d can influence antigen presentation mainly when the endocytic pathway is required. Flow cytometry analysis can provide additional...

Influence of elemental diffusion on low temperature formation of MgH2 in TiMn1.3T0.2-Mg (T = 3d-transition elements)

International Nuclear Information System (INIS)

Yamamoto, K.; Tanioka, S.; Tsushio, Y.; Shimizu, T.; Morishita, T.; Orimo, S.; Fujii, H.

1996-01-01

In order to examine the influence of the elemental diffusion from the host compound into the Mg region on low temperature formation of MgH 2 , we have investigated the hydriding properties and the microstructures of the composite materials TiMn 1.3 T 0.2 -Mg (T = V, Cr, Mn, Fe, Co, Ni and Cu). MgH 2 is formed at 353 K in all composite materials. Of all the substitutions, the amount of MgH 2 is the largest in the case of the Cu substitution, which originates from the existence of the Mg-Mg 2 Cu eutectic formed by Cu diffusion from the host compound TiMn 1.3 Cu 0.2 into the Mg region during the liquid phase sintering. In addition, the hydrogen capacity of TiMn 1.3 Cu 0.2 -Mg (that is TiMn 1.3 Cu 0.1 -(Mg+Mg 2 Cu) after the sintering) easily saturates in comparison with TiMn 1.5 -(Mg+Mg 2 Cu) without Cu diffusion. It is concluded that Cu diffusion promotes the mobility of hydrogen atoms at the complex interface between the host compound and the Mg region. (orig.)

Human T-cell leukemia virus type 1 Tax and cell cycle progression: role of cyclin D-cdk and p110Rb.

Science.gov (United States)

Neuveut, C; Low, K G; Maldarelli, F; Schmitt, I; Majone, F; Grassmann, R; Jeang, K T

1998-06-01

Human T-cell leukemia virus type 1 is etiologically linked to the development of adult T-cell leukemia and various human neuropathies. The Tax protein of human T-cell leukemia virus type I has been implicated in cellular transformation. Like other oncoproteins, such as Myc, Jun, and Fos, Tax is a transcriptional activator. How it mechanistically dysregulates the cell cycle is unclear. Previously, it was suggested that Tax affects cell-phase transition by forming a direct protein-protein complex with p16(INK4a), thereby inactivating an inhibitor of G1-to-S-phase progression. Here we show that, in T cells deleted for p16(INK4a), Tax can compel an egress of cells from G0/G1 into S despite the absence of serum. We also show that in undifferentiated myocytes, expression of Tax represses cellular differentiation. In both settings, Tax expression was found to increase cyclin D-cdk activity and to enhance pRb phosphorylation. In T cells, a Tax-associated increase in steady-state E2F2 protein was also documented. In searching for a molecular explanation for these observations, we found that Tax forms a protein-protein complex with cyclin D3, whereas a point-mutated and transcriptionally inert Tax mutant failed to form such a complex. Interestingly, expression of wild-type Tax protein in cells was also correlated with the induction of a novel hyperphosphorylated cyclin D3 protein. Taken together, these findings suggest that Tax might directly influence cyclin D-cdk activity and function, perhaps by a route independent of cdk inhibitors such as p16(INK4a).

In vitro assessment of MRI safety at 1.5 T and 3.0 T for bone-anchored hearing aid implant

Energy Technology Data Exchange (ETDEWEB)

Yeon, Kyoo Jin; KIm, Hyun Soo; Lee, Seung Keun [Dept. of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Tae Soo [Dept. of Biomedical Engineering, Chungbuk National University, Cheongju (Korea, Republic of)

2017-03-15

The aim of this study was to evaluate Magnetic Resonance Imaging safety by measuring the translational attraction, torque and susceptibility artifact for Bone-Anchored Hearing Aid (BAHA) implant at 1.5 T and 3.0 T MRI by standard criteria. In vitro assessment tools were made of acrylic-resin by American Society for Testing and Materials (ASTM) F2052-06 and F2119-07 standard. Translational attraction of BAHA implant was measured by the maximum deflection angle at 96 cm position, where the magnetically induced deflection was the greatest. The torque was assessed by the qualitative criteria of evaluating the alignment and rotation pattern, when the BAHA implant was positioned on a line with 45° intervals inside the circular container in the center of the bore. The susceptibility artifact images were obtained using the hanged test tool, which was filled with CuSO4 solution. And then the artifact size was measured using Susceptibility Artifact Measurement (SAM) software. In results, the translational attraction was 0 mm at both 1.5 T and 3.0 T and the torque was 0(no torque) at 1.5 T, and +1(mild torque) at 3.0 T. The size of susceptibility artifacts was between 13.20 mm and 38.91 mm. Therefore, The BAHA implant was safe for the patient in clinical MR environment.

In vitro assessment of MRI safety at 1.5 T and 3.0 T for bone-anchored hearing aid implant

International Nuclear Information System (INIS)

Yeon, Kyoo Jin; KIm, Hyun Soo; Lee, Seung Keun; Lee, Tae Soo

2017-01-01

The aim of this study was to evaluate Magnetic Resonance Imaging safety by measuring the translational attraction, torque and susceptibility artifact for Bone-Anchored Hearing Aid (BAHA) implant at 1.5 T and 3.0 T MRI by standard criteria. In vitro assessment tools were made of acrylic-resin by American Society for Testing and Materials (ASTM) F2052-06 and F2119-07 standard. Translational attraction of BAHA implant was measured by the maximum deflection angle at 96 cm position, where the magnetically induced deflection was the greatest. The torque was assessed by the qualitative criteria of evaluating the alignment and rotation pattern, when the BAHA implant was positioned on a line with 45° intervals inside the circular container in the center of the bore. The susceptibility artifact images were obtained using the hanged test tool, which was filled with CuSO4 solution. And then the artifact size was measured using Susceptibility Artifact Measurement (SAM) software. In results, the translational attraction was 0 mm at both 1.5 T and 3.0 T and the torque was 0(no torque) at 1.5 T, and +1(mild torque) at 3.0 T. The size of susceptibility artifacts was between 13.20 mm and 38.91 mm. Therefore, The BAHA implant was safe for the patient in clinical MR environment

Efficacy and safety of insulin pump treatment in adult T1DM patients--influence of age and social environment.

Science.gov (United States)

Grzanka, Małgorzata; Matejko, Bartłomiej; Cyganek, Katarzyna; Kozek, Elżbieta; Małecki, Maciej T; Klupa, Tomasz

2012-01-01

Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals. Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment. The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively). The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.

Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA Expression in Poultry

NARCIS (Netherlands)

Pavlova, Ivelina; Milanova, Aneliya; Danova, Svetla; Fink-Gremmels, Johanna

2016-01-01

Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial peptide 2 (LEAP-2) in chickens can be influenced by food deprivation, pathological conditions and drug administration. Effect of three putative probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1

Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion

Directory of Open Access Journals (Sweden)

Fatou K. Ndiaye

2017-06-01

Full Text Available Objectives: Genome-wide association studies (GWAS have identified >100 loci independently contributing to type 2 diabetes (T2D risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells. Methods: The expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-βH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-βH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function. Results: We found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-βH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (CDKN2A, GCK, HNF4A, KCNK16, SLC30A8, TBC1D4, and TCF19 with already known expression and/or function in beta cells changed insulin secretion, supporting our functional approach. We showed first evidence for a role in insulin secretion of four candidate T2D-susceptibility genes (PRC1, SRR, ZFAND3, and ZFAND6 with no previous knowledge of presence and function in beta cells. RNA-seq in EndoC-βH1 cells with decreased expression of PRC1, SRR, ZFAND6, or ZFAND3 identified specific gene networks related to T2D pathophysiology. Finally, a positive correlation between the expression of Ins2 and the

Exploring correlates of diabetes-related stress among adults with Type 1 diabetes in the T1D exchange clinic registry.

Science.gov (United States)

Boden, Matthew Tyler; Gala, Sasha

2018-04-01

To explore relations between diabetes-related stress and multiple sociodemographic, diabetes health, other health, and treatment-related variables among a large sample of adults with Type 1 Diabetes (T1D). The sample consisted of 10,821 adults (over 18 years old) enrolled in the T1D Exchange Clinic Registry. The T1D Exchange clinic network consists of 67 diabetes clinical centers throughout the United States selected to broadly represent pediatric and adult patients with T1D. Variables were assessed through participant self-report and extraction of clinic chart data. Univariate and multiple linear regression (with simultaneous entry of all predictors) analyses were conducted. Robustly associated with increased diabetes-related stress across analyses were multiple sociodemographic (female [vs. male], native Hawaiian/other Pacific islander [vs. white/Caucasian], decreased age and diabetes duration), diabetes health (higher HbA1c), other health (lower general health, presence of major life stress and depression, less physical activity), and treatment related variables (use of injections/pen or combination injection/pen/pump [vs. pump], use of CGM, increased frequency of missing insulin doses and BG checking, decreased frequency of BG checking prior to bolus, receipt of mental health treatment). We replicated and extended research demonstrating that diabetes-related stress among people with T1D occurs at higher levels among those with particular sociodemographic characteristics and is associated with a range poorer diabetes health and other health variables, and multiple treatment-related variables. The strong incremental prediction of diabetes-related stress by multiple variables in our study suggests that a multi-variable, personalized approach may increase the effectiveness of treatments for diabetes-related stress. Published by Elsevier B.V.

Rôle de la société civile pour ce qui est d'influencer les politiques de ...

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

Rôle de la société civile pour ce qui est d'influencer les politiques de santé publique en faveur des femmes autochtones du Mexique. Au Mexique, les iniquités relatives à l'accès aux services de santé et aux services connexes sont sensiblement plus marquées chez les populations autochtones, et en particulier chez les ...

Role of combined DWIBS/3D-CE-T1w whole-body MRI in tumor staging: Comparison with PET-CT

International Nuclear Information System (INIS)

Manenti, Guglielmo; Cicciò, Carmelo; Squillaci, Ettore; Strigari, Lidia; Calabria, Ferdinando; Danieli, Roberta

2012-01-01

Objectives: To assess the diagnostic performance of whole-body magnetic resonance imaging (WB-MRI) by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in malignant tumor detection and the potential diagnostic advantages in generating fused DWIBS/3D-contrast enhanced T1w (3D-CE-T1w) images. Methods: 45 cancer patients underwent 18F-FDG PET-CT and WB-MRI for staging purpose. Fused DWIBS/3D-CE T1w images were generated off-line. 3D-CE-T1w, DWIBS images alone and fused with 3D-CE T1w were compared by two readers groups for detection of primary diseases and local/distant metastases. Diagnostic performance between the three WB-MRI data sets was assessed using receiver operating characteristic (ROC) curve analysis. Imaging exams and histopathological results were used as standard of references. Results: Areas under the ROC curves of DWIBS vs. 3D-CE-T1w vs. both sequences in fused fashion were 0.97, 0.978, and 1.00, respectively. The diagnostic performance in tumor detection of fused DWIBS/3D-CE-T1w images were statistically superior to DWIBS (p < 0.001) and 3D-CE-T1w (p ≤ 0.002); while the difference between DWIBS and 3D-CE-T1w did not show statistical significance difference. Detection rates of malignancy did not differ between WB-MRI with DWIBS and 18F-FDG PET-CT. Conclusion: WB-MRI with DWIBS is to be considered as alternative tool to conventional whole-body methods for tumor staging and during follow-up in cancer patients.

Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms.

Science.gov (United States)

Wolfensberger, Aline; Sax, Hugo; Weber, Rainer; Zbinden, Reinhard; Kuster, Stefan P; Hombach, Michael

2013-01-01

We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.

Susceptibility to stress corrosion in stainless steels type AISI 321 and 12X18H10T used in PWR type reactors (WWER)

International Nuclear Information System (INIS)

Matadamas C, N.

1995-01-01

Titanium stabilized stainless steels have been utilized in sovietic pressurized water reactors (VVER) for avoid the susceptibility to Intergranular Corrosion (IGC) present in other austenitic stainless steels. However the Intergranular Corrosion resistance of this kind of materials has been questioned because of Intergranular Stress Corrosion Cracking failures (IGSCC) have been reported. This paper study the electrochemical behavior of the AISI 321 stainless steel in a H 3 BO 3 Solution contaminated with chlorides and its susceptibility to Intergranular Corrosion.Electrochemical prediction diagrams of the stainless steels AISI 321 and 12X18H10T (sovietic) sensitized (600 Centigrade, 3 h.) were compared. Cylindrical and conical samples were used in Slow Strain Rate Tests (SSRT), to determine the susceptibility to Stress Corrosion Cracking (SCC) in AISI 321 and 12X18H10T stainless steels. The results obtained showed that the temperature of the solution is a very important factor to detect this susceptibility. Fractography studies on the fracture surfaces of the samples obtained in the SSRT at high temperature were realized. Corrosion velocities of both AISI 321 and 12X18H10T stainless steels were determined using conical samples in the CERT system at high temperature. E.D.A.X. analysis was employed in both AISI 321 and 12X18H10T stainless steels in order to explain the degree of sensitization. (Author)

Cross-talk between cd1d-restricted nkt cells and γδ cells in t regulatory cell response

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Huber Sally A

2011-01-01

Full Text Available Abstract CD1d is a non-classical major histocompatibility class 1-like molecule which primarily presents either microbial or endogenous glycolipid antigens to T cells involved in innate immunity. Natural killer T (NKT cells and a subpopulation of γδ T cells expressing the Vγ4 T cell receptor (TCR recognize CD1d. NKT and Vγ4 T cells function in the innate immune response via rapid activation subsequent to infection and secrete large quantities of cytokines that both help control infection and modulate the developing adaptive immune response. T regulatory cells represent one cell population impacted by both NKT and Vγ4 T cells. This review discusses the evidence that NKT cells promote T regulatory cell activation both through direct interaction of NKT cell and dendritic cells and through NKT cell secretion of large amounts of TGFβ, IL-10 and IL-2. Recent studies have shown that CD1d-restricted Vγ4 T cells, in contrast to NKT cells, selectively kill T regulatory cells through a caspase-dependent mechanism. Vγ4 T cell elimination of the T regulatory cell population allows activation of autoimmune CD8+ effector cells leading to severe cardiac injury in a coxsackievirus B3 (CVB3 myocarditis model in mice. CD1d-restricted immunity can therefore lead to either immunosuppression or autoimmunity depending upon the type of innate effector dominating during the infection.

Evaluation of prospective motion correction of high-resolution 3D-T2-FLAIR acquisitions in epilepsy patients.

Science.gov (United States)

Vos, Sjoerd B; Micallef, Caroline; Barkhof, Frederik; Hill, Andrea; Winston, Gavin P; Ourselin, Sebastien; Duncan, John S

2018-03-02

T2-FLAIR is the single most sensitive MRI contrast to detect lesions underlying focal epilepsies but 3D sequences used to obtain isotropic high-resolution images are susceptible to motion artefacts. Prospective motion correction (PMC) - demonstrated to improve 3D-T1 image quality in a pediatric population - was applied to high-resolution 3D-T2-FLAIR scans in adult epilepsy patients to evaluate its clinical benefit. Coronal 3D-T2-FLAIR scans were acquired with a 1mm isotropic resolution on a 3T MRI scanner. Two expert neuroradiologists reviewed 40 scans without PMC and 40 with navigator-based PMC. Visual assessment addressed six criteria of image quality (resolution, SNR, WM-GM contrast, intensity homogeneity, lesion conspicuity, diagnostic confidence) on a seven-point Likert scale (from non-diagnostic to outstanding). SNR was also objectively quantified within the white matter. PMC scans had near-identical scores on the criteria of image quality to non-PMC scans, with the notable exception that intensity homogeneity was generally worse. Using PMC, the percentage of scans with bad image quality was substantially lower than without PMC (3.25% vs. 12.5%) on the other five criteria. Quantitative SNR estimates revealed that PMC and non-PMC had no significant difference in SNR (P=0.07). Application of prospective motion correction to 3D-T2-FLAIR sequences decreased the percentage of low-quality scans, reducing the number of scans that need to be repeated to obtain clinically useful data. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Influence of tobacco marketing and exposure to smokers on adolescent susceptibility to smoking.

Science.gov (United States)

Evans, N; Farkas, A; Gilpin, E; Berry, C; Pierce, J P

1995-10-18

Today the uptake of smoking is primarily an adolescent pursuit. Awareness of tobacco advertising and promotion is high, and evidence suggests that it plays a role in adolescent smoking uptake. We evaluated the influence of tobacco advertising and promotion and exposure to smokers on never-smoking adolescents' susceptibility to smoking. We used data on 3536 adolescent never smokers (those who had never even puffed on a cigarette) from the 1993 California Tobacco Survey. That survey questioned adolescents about smoking history and inclinations. For this analysis, we defined as susceptible to smoking those never smokers who said on the survey that they could not rule out independently deciding to try a cigarette soon or smoking one offered by a friend. Also for this analysis, we devised two indices: 1) a 5-point index of an individual's receptivity to tobacco advertising as determined by the number of positive responses to five survey items (recognition of advertising messages, having a favorite advertisement, naming a brand he/she might buy, owning a tobacco-related promotional item, and willingness to use a tobacco-related promotional item) and 2) an index classifying an individual's reported exposure to family and peer smoking into one of four levels. Using logistic regression, we assessed the independent importance of our indices in predicting susceptibility to smoking after adjustment for sociodemographic variables, including age, sex, and race/ethnicity, and for perceived school performance. Tests of statistical significance were two-sided. Receptivity to tobacco advertising and exposure to smokers were independently associated with susceptibility to smoking, but the relationship appeared stronger for receptivity to advertising. Adolescents exposed to family members and peers (n = 489) who smoked were 1.89 (95% confidence interval [CI] = 1.30-2.74) times as likely to be susceptible, whereas adolescents who scored 4 or more on the Index of Receptivity to Tobacco

Rapid T1 quantification based on 3D phase sensitive inversion recovery

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Warntjes Marcel JB

2010-08-01

Full Text Available Abstract Background In Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR. Equations were derived to take the acquisition and saturation effects on the magnetization into account. Methods The accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1 over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images. Results The fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images. Conclusions The method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

Characterizing diabetes burnout in parents of youth with type 1 diabetes (T1D)[abstract

Science.gov (United States)

Managing T1D is complex and requires round-the-clock attention, much of which falls to parents. Parental stress and family conflict about diabetes are associated with suboptimal youth self management and glycemic outcomes, yet little research has described parents' experiences with burnout or tested...

Influence of the 3D-2D crossover on the critical current of Nb/Cu multilayers

DEFF Research Database (Denmark)

Krasnov, V. M.; Pedersen, Niels Falsig; Oboznov, V. A.

1994-01-01

We report the experimental observation of the Josephson critical current across layers, I(c) perpendicular-to, for Nb/Cu multilayers. Unique samples with a small cross section (20 mum in diameter) consisting of ten Nb/Cu junctions were fabricated for such measurements. A strong influence of the d......We report the experimental observation of the Josephson critical current across layers, I(c) perpendicular-to, for Nb/Cu multilayers. Unique samples with a small cross section (20 mum in diameter) consisting of ten Nb/Cu junctions were fabricated for such measurements. A strong influence...... of the dimensional 3D-2D cross-over on the I(c)perpendicular-to was observed. Thus, as the temperature becomes smaller than T2D, hysteresis in the current-voltage characteristic appears and the behavior of the temperature dependence of the I(c)perpendicular-to changes. For T > T2D the diminishing of the hysteresis...... is caused by a sharp decrease of the junction capacitance in the 3D regime when the sample becomes uniform across layers. Calculation of the critical-current temperature dependence I(c)perpendicular-to (T) for our multilayers was made. An agreement between experimental and theoretical dependencies I...

The value of 3D T1-weighted gradient-echo MR imaging for evaluation of the appendix during pregnancy: preliminary results

Energy Technology Data Exchange (ETDEWEB)

Jang, Kyung Mi; Kim, Seong Hyun; Choi, Dongil; Lee, Soon Jin; Rhim, Hyunchul; Park, Min Jung (Depts. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan Univ. School of Medicine, Seoul (Korea, Republic of)), email: kshyun@skku.edu

2011-10-15

Background The use of oral contrast has been essential for the identification of a normal appendix on MR imaging during pregnancy. However, stool could be used as a positive oral contrast as it is characterized by a relatively high signal on T1-weighted imaging, and 3D T1-weighted gradient-echo (T1W-GRE) MR imaging has been used to evaluate 3 mm diameter intestines in fetuses. Purpose To evaluate the added value of 3D T1W-GRE MR imaging in combination with T2-weighted imaging (T2WI) compared to T2WI alone for evaluating the appendix during pregnancy. Material and Methods Eighteen consecutive pregnant patients who were clinically suspected of having acute appendicitis underwent appendix MR imaging which included T2WI with or without spectral presaturation attenuated inversion-recovery (SPAIR) fat suppression, and 3D T1W-GRE with SPAIR fat suppression. Two radiologists reviewed the two image sets (the T2WI set and the combined set of T2WI and 3D T1W-GRE images). Pathologic and clinical results served as the reference standard. The differences in the degree of visibility of the appendix and confidence scale for diagnosing acute appendicitis between two image sets were compared by using the paired Wilcoxon signed rank test. Results For both reviewers, the degree of visibility of the appendix using the combined T2WI and 3D T1W-GRE images was significantly higher than using T2WI alone (P < 0.01), and the confidence levels for acute appendicitis using combined T2WI and 3D T1W-GRE images were significantly different from those using T2WI alone (P < 0.01). In the 13 patients with a normal appendix, both reviewers showed improved confidence levels for appendicitis using combined T2WI and 3D T1W-GRE images than T2WI alone. Conclusion Adding 3D T1W-GRE images to T2WI is helpful for identification of the appendix, as compared to T2WI alone in pregnant women without ingestion of oral contrast material. This may improve diagnostic confidence for acute appendicitis in pregnant

A pilot interventional study to evaluate the impact of cholecalciferol treatment on HbA1c in type 1 diabetes (T1D

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R Perchard

2017-05-01

Full Text Available Background: Higher 25(OHD3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c. Aims: (1 To assess the baseline 25(OHD3 status in a Manchester cohort of children with type 1 diabetes (T1D. (2 To determine the effect of cholecalciferol administration on HbA1c. Methods: Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OHD3 level 10 years units. HbA1c levels before and after treatment were recorded. Results: Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OHD3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OHD3 level and HbA1c (r = −0.484, P < 0.01. In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328 or at 1 year (t = −1.173, P = 0.248 before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level. Conclusion: We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

Association between RAS Gene Polymorphisms (ACE I/D, AGT M235T and Henoch-Schönlein Purpura in a Turkish Population

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Sinem Nalbantoglu

2013-01-01

Full Text Available Henoch-Schönlein purpura (HSP is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p = 0.003 and allele frequencies (p 0.05 and allele frequencies (p > 0.05 of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p = 0.019, OR: 2.288, 95% CI: 1.136–4.609 and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632–3.0912, p = 0.001 while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p = 0.312, OR: 1.3905, 95% CI: 0.7326–2.6391 and T allele (OR: T vs. M: 1.065, 95% CI: 0.729–1.557, p = 0.743. Furthermore, when patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility.

An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

Science.gov (United States)

Hartman, Sarah; Belsky, Jay

2016-12-01

An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.

Comparison of susceptibility to pitting corrosion of AA2024-T4, AA7075-T651 and AA7475-T761 aluminium alloys in neutral chloride solutions using electrochemical noise analysis

International Nuclear Information System (INIS)

Na, Kyung-Hwan; Pyun, Su-Il

2008-01-01

The susceptibility to pitting corrosion of AA2024-T4, AA7075-T651 and AA7475-T761 aluminium alloys was investigated in aqueous neutral chloride solution for the purpose of comparison using electrochemical noise measurement. The experimentally measured electrochemical noises were analysed based upon the combined stochastic theory and shot-noise theory using the Weibull distribution function. From the occurrence of two linear regions on one Weibull probability plot, it was suggested that there existed two stochastic processes of uniform corrosion and pitting corrosion; pitting corrosion was distinguished from uniform corrosion in terms of the frequency of events in the stochastic analysis. Accordingly, the present analysis method allowed us to investigate pitting corrosion independently. The susceptibility to pitting corrosion was appropriately evaluated by determining pit embryo formation rate in the stochastic analysis. The susceptibility was decreased in the following order: AA2024-T4 (the naturally aged condition), AA7475-T761 (the overaged condition) and AA7075-T651 (the near-peak-aged condition)

Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms.

Directory of Open Access Journals (Sweden)

Aline Wolfensberger

Full Text Available OBJECTIVE: We studied whether the change in antibiotic susceptibility testing (AST guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. METHODS: Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A and after (period B changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011 guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013 guidelines. RESULTS: The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009 vs. 93.1% (EUCAST 1.3, P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009 vs. 90.5% (EUCAST 1.3, P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009 vs. 78.3% (EUCAST 1.3, P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009 and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3. CONCLUSIONS: The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.

Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

Science.gov (United States)

Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

2017-07-05

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

Asthma susceptible genes in Chinese population: A meta-analysis

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He Chao

2010-09-01

Full Text Available Abstract Background Published data regarding the associations between genetic variants and asthma risk in Chinese population were inconclusive. The aim of this study was to investigate asthma susceptible genes in Chinese population. Methods The authors conducted 18 meta-analyzes for 18 polymorphisms in 13 genes from eighty-two publications. Results Seven polymorphisms were found being associated with risk of asthma, namely: A Disintegrin and Metalloprotease 33 (ADAM33 T1-C/T (odds ratio [OR] = 6.07, 95% confidence interval [CI]: 2.69-13.73, Angiotensin-Converting Enzyme (ACE D/I (OR = 3.85, 95%CI: 2.49-5.94, High-affinity IgE receptor β chain (FcεRIβ -6843G/A (OR = 1.49, 95%CI: 1.01-2.22, Interleukin 13(IL-13 -1923C/T (OR = 2.99, 95%CI: 2.12-4.24, IL-13 -2044A/G (OR = 1.49, 95%CI: 1.07-2.08, Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES -28C/G (OR = 1.64, 95%CI: 1.09-2.46, Tumor Necrosis Factor-α (TNF-α -308G/A(OR = 1.42, 95%CI: 1.09, 1.85. After subgroup analysis by age, the ACE D/I, β2-Adrenergic Receptor (β2-AR -79G/C, TNF-α -308G/A, Interleukin 4 receptor(IL-4R -1902G/A and IL-13 -1923C/T polymorphisms were found significantly associated with asthma risk in Chinese children. In addition, the ACE D/I, FcεRIβ -6843G/A, TNF-α -308G/A, IL-13 -1923C/T and IL-13 -2044A/G polymorphisms were associated with asthma risk in Chinese adults. Conclusion ADAM33, FcεRIβ, RANTES, TNF-α, ACE, β2-AR, IL-4R and IL-13 genes could be proposed as asthma susceptible genes in Chinese population. Given the limited number of studies, more data are required to validate these associations.

Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T-cell receptor

Energy Technology Data Exchange (ETDEWEB)

López-Sagaseta, Jacinto; Sibener, Leah V.; Kung, Jennifer E.; Gumperz, Jenny; Adams, Erin J. (UC); (UW-MED)

2014-10-02

Invariant Natural Killer T (iNKT) cells use highly restricted {alpha}{beta} T cell receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules. Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d presenting LPC adopts an altered conformation from that of CD1d presenting glycolipid antigens, with a shifted {alpha}1 helix resulting in an open A pocket. Binding of the iNKT TCR requires a 7-{angstrom} displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop footprint on CD1d-LPC is anchored by the conserved positioning of the CDR3{alpha} loop, whereas the remaining CDR loops are shifted, due in part to amino-acid differences in the CDR3{beta} and J{beta} segment used by this iNKT TCR. These findings provide insight into how lysophospholipids are presented by human CD1d molecules and how this complex is recognized by some, but not all, human iNKT cells.

Role of sex hormones and the vaginal microbiome in susceptibility and mucosal immunity to HIV-1 in the female genital tract.

Science.gov (United States)

Vitali, Danielle; Wessels, Jocelyn M; Kaushic, Charu

2017-09-12

While the prevalence of Human immunodeficiency virus-1 (HIV-1) infection has stabilized globally, it continues to be the leading cause of death among women of reproductive age. The majority of new infections are transmitted heterosexually, and women have consistently been found to be more susceptible to HIV-1 infection during heterosexual intercourse compared to men. This emphasizes the need for a deeper understanding of how the microenvironment in the female genital tract (FGT) could influence HIV-1 acquisition. This short review focuses on our current understanding of the interplay between estrogen, progesterone, and the cervicovaginal microbiome and their immunomodulatory effects on the FGT. The role of hormonal contraceptives and bacterial vaginosis on tissue inflammation, T cell immunity and HIV-1 susceptibility is discussed. Taken together, this review provides valuable information for the future development of multi-purpose interventions to prevent HIV-1 infection in women.

Fnip1 regulates skeletal muscle fiber type specification, fatigue resistance, and susceptibility to muscular dystrophy

Science.gov (United States)

Reyes, Nicholas L.; Banks, Glen B.; Tsang, Mark; Margineantu, Daciana; Gu, Haiwei; Djukovic, Danijel; Chan, Jacky; Torres, Michelle; Liggitt, H. Denny; Hirenallur-S, Dinesh K.; Hockenbery, David M.; Raftery, Daniel; Iritani, Brian M.

2015-01-01

Mammalian skeletal muscle is broadly characterized by the presence of two distinct categories of muscle fibers called type I “red” slow twitch and type II “white” fast twitch, which display marked differences in contraction strength, metabolic strategies, and susceptibility to fatigue. The relative representation of each fiber type can have major influences on susceptibility to obesity, diabetes, and muscular dystrophies. However, the molecular factors controlling fiber type specification remain incompletely defined. In this study, we describe the control of fiber type specification and susceptibility to metabolic disease by folliculin interacting protein-1 (Fnip1). Using Fnip1 null mice, we found that loss of Fnip1 increased the representation of type I fibers characterized by increased myoglobin, slow twitch markers [myosin heavy chain 7 (MyH7), succinate dehydrogenase, troponin I 1, troponin C1, troponin T1], capillary density, and mitochondria number. Cultured Fnip1-null muscle fibers had higher oxidative capacity, and isolated Fnip1-null skeletal muscles were more resistant to postcontraction fatigue relative to WT skeletal muscles. Biochemical analyses revealed increased activation of the metabolic sensor AMP kinase (AMPK), and increased expression of the AMPK-target and transcriptional coactivator PGC1α in Fnip1 null skeletal muscle. Genetic disruption of PGC1α rescued normal levels of type I fiber markers MyH7 and myoglobin in Fnip1-null mice. Remarkably, loss of Fnip1 profoundly mitigated muscle damage in a murine model of Duchenne muscular dystrophy. These results indicate that Fnip1 controls skeletal muscle fiber type specification and warrant further study to determine whether inhibition of Fnip1 has therapeutic potential in muscular dystrophy diseases. PMID:25548157

Chemokines and Chemokine Receptors in Susceptibility to HIV-1 Infection and Progression to AIDS

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Animesh Chatterjee

2012-01-01

Full Text Available A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

OpenAIRE

Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AL

2014-01-01

Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populatio...

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

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Maria José Franco Brochado

2016-02-01

Full Text Available Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1 is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GTn, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively, and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GTn polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66. Patients carrying the 274T allele (p = 0.04; OR = 1.49 and TT homozygosis (p = 0.02; OR = 2.46, such as the 469+14C allele (p = 0.03; OR = 1.53 of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GTn polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Polaron Hopping in Nano-scale Poly(dA–Poly(dT DNA

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Singh Mahi

2010-01-01

Full Text Available Abstract We investigate the current–voltage relationship and the temperature-dependent conductance of nano-scale samples of poly(dA–poly(dT DNA molecules. A polaron hopping model has been used to calculate the I–V characteristic of nano-scale samples of DNA. This model agrees with the data for current versus voltage at temperatures greater than 100 K. The quantities G 0 , i 0 , and T 1d are determined empirically, and the conductivity is estimated for samples of poly(dA–poly(dT.

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

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Yamakawa-Kobayashi Kimiko

2012-02-01

Full Text Available Abstract Background Type 2 diabetes mellitus (T2DM is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. Methods Single nucleotide polymorphisms (SNPs in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects. Results We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P P P = 0.88 for trend. Conclusions Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.

Helper T cell subpopulations from women are more susceptible to the toxic effect of sodium arsenite in vitro

International Nuclear Information System (INIS)

Vega, Libia; Montes de Oca, Pavel; Saavedra, Rafael; Ostrosky-Wegman, Patricia

2004-01-01

Arsenic is known to produce inhibition as well as induction of proliferative responses in animal and human cells depending on the doses. Despite the amount of information on the immunotoxic effects of arsenic exposure in different animal models, little is known in humans. Arsenic susceptibility of lymphocyte subpopulations (T helper (Th), CD4+; T cytotoxic (Tc), CD8+) and whether arsenic effects are gender related are still to be determined. This work evaluated the in vitro toxicity of sodium arsenite on human T lymphocyte subpopulations from men and women. Peripheral blood mononuclear cells (PBMC) obtained from healthy young men and women were treated with sodium arsenite (0.01, 0.1, and 1 μM). We assessed cell viability, cell proliferation, and the proportion of Th and Tc cells after 48 or 72 h of arsenic exposure in resting and phytohemagglutinin M (PHA)-activated PBMC. We observed that sodium arsenite at 1 μM was more toxic for Th than for Tc cells in PBMC from women. Besides, T lymphocytes from women were more affected by the cell proliferation inhibition induced by arsenic, suggesting that women could be more susceptible to the toxic and immunotoxic effects caused by arsenic exposure

The extended family of CD1d-restricted T cells: sifting through a mixed bag of TCRs, antigens and functions

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Elodie eMacho-Fernandez

2015-07-01

Full Text Available Natural killer T (NKT cells comprise a family of specialized T cells that recognize lipid antigens presented by CD1d. Based on their T cell receptor (TCR usage and antigen-specificities, CD1d-restricted NKT cells have been divided into two main subsets: type I NKT cells that use a canonical invariant TCR α-chain and recognize α-galactosylceramide (α-GalCer, and type II NKT cells that use a more diverse αβ TCR repertoire and do not recognize α-GalCer. In addition, α-GalCer-reactive NKT cells that use non-canonical αβ TCRs and CD1d-restricted T cells that use γδ or δ/αβ TCRs have recently been identified, revealing further diversity among CD1d-restricted T cells. Importantly, in addition to their distinct antigen specificities, functional differences are beginning to emerge between the different members of the CD1d-restricted T cell family. In this review, while using type I NKT cells as comparison, we will focus on type II NKT cells and the other non-invariant CD1d-restricted T cell subsets, and discuss our current understanding of the antigens they recognize, the formation of stimulatory CD1d/antigen complexes, the modes of TCR-mediated antigen recognition, and the mechanisms and consequences of their activation that underlie their function in antimicrobial responses, antitumor immunity, and autoimmunity.

IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

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Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

2009-01-01

Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

Multispectroscopic methods reveal different modes of interaction of anti cancer drug mitoxantrone with Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT).

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Awasthi, Pamita; Dogra, Shilpa; Barthwal, Ritu

2013-10-05

The interaction of mitoxantrone with alternating Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT) duplex has been studied by absorption, fluorescence and Circular Dichroism (CD) spectroscopy at Drug to Phosphate base pair ratios D/P=20.0-0.04. Binding to GC polymer occurs in two distinct modes: partial stacking characterized by red shifts of 18-23nm at D/P=0.2-0.8 and external binding at D/P=1.0-20.0 whereas that to AT polymer occurs externally in the entire range of D/P. The binding constant and number of binding sites is 3.7×10(5)M(-1), 0.3 and 1.3× 10(4)M(-1), 1.5 in GC and AT polymers, respectively at low D/P ratios. CD binding isotherms show breakpoints at D/P=0.1, 0.5 and 0.25, 0.5 in GC and AT polymers, respectively. The intrinsic CD bands indicate that the distortions in GC polymer are significantly higher than that in AT polymer. Docking studies show partial insertion of mitoxantrone rings between to GC base pairs in alternating GC polymer. Side chains of mitoxantrone interact specifically with base pairs and DNA backbone. The studies are relevant to the understanding of suppression or inhibition of DNA cleavage on formation of ternary complex with topoisomerase-II enzyme and hence the anti cancer action. Copyright © 2013 Elsevier B.V. All rights reserved.

Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumours: clinical implications and prognostic significance.

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Blanca Pedregosa, A M; Sánchez-González, Á; Carrasco Valiente, J; Ruiz García, J M; Gómez Gómez, E; López Beltrán, A; Requena Tapia, M J

2017-04-01

To determine the differential protein expression of biomarkers FGFR3, PI3K (subunits PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 and cyclins D1 and D3 in T1 bladder cancer versus healthy tissue and to study their potential role as early recurrence markers. This is a prospective study that employed a total of 67 tissue samples (55 cases of T1 bladder tumours that underwent transurethral resection and 12 cases of adjacent healthy mucosa). The protein expression levels were assessed using Western blot, and the means and percentages were compared using Student's t-test and the chi-squared test. The survival analysis was conducted using the Kaplan-Meier method and the log-rank test. Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumour tissue than in the healthy mucosa. However, these differences were not significant for PI3Kp85 and AKT. We observed statistically significant correlations between early recurrence and PI3Kp110α, PI3KClassIII, PI3Kp85 and AKT (P=.003, P=.045, P=.050 and P=.028, respectively), between the tumour type (primary vs. recurrence) and cyclin D3 (P=.001), between the tumour size and FGFR3 (P=.035) and between multifocality and cyclin D1 (P=.039). The survival analysis selected FGFR3 (P=.024), PI3Kp110α (P=.014), PI3KClassIII (P=.042) and AKT (P=.008) as markers of early-recurrence-free survival. There is an increase in protein expression levels in bladder tumour tissue. The overexpression of FGFR3, PI3Kp110α, PI3KClassIII and AKT is associated with increased early-recurrence-free survival for patients with T1 bladder tumours. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Associations between interleukin-1 polymorphisms and susceptibility to vasculitis: a meta-analysis.

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Song, G G; Kim, J-H; Lee, Y H

2016-05-01

The objective of this study was to determine whether interleukin-1 (IL-1) polymorphisms are associated with susceptibility to vasculitis. A meta-analysis was conducted to investigate possible associations between IL-1A, IL-1B, and IL-1 receptor antagonist (IL1RN) polymorphisms and vasculitis. A total of 17 studies involving 1384 vasculitis cases [Behçet's disease (BD), IgA vasculitis, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), Kawasaki disease (KD), giant cell arteritis, and Takayasu's arteritis] and 2710 controls were included in the meta-analysis. This analysis showed an association between BD and the TT + TC genotypes of the IL-1A-889 C/T polymorphism in the entire study population [odds ratio (OR) = 0.623, 95 % CI = 0.395-0.981, p = 0.045), and a trend toward an association in a Turkish population (OR = 0.578, 95 % CI = 0.331-1.010, p = 0.054). A meta-analysis of the IL1RN polymorphism revealed no association with vasculitis in all study subjects (OR for IL1RN*2 = 0.904, 95 % CI = 0.626-1.304, p = 0.588). However, stratification by ethnicity revealed a significant association between the IL1RN*2 allele and vasculitis including AAV, BD, KD in Asians (OR = 2.393, 95 % CI = 1.429-4.006, p = 0.001), but not in Caucasian and Turkish populations (OR = 0.776, 95 % CI = 0.487-1.238, p = 0.288; OR = 0.914, 95 % CI = 0.667-1.252, p = 0.576, respectively). No association was found between vasculitis and the IL-1B-511 C/T polymorphism, or the IL-1B+3953 C/T polymorphism. This meta-analysis suggests that the IL-1A-889 C/T polymorphism is associated with susceptibility to BD, and that the IL1RN*2 allele is associated with susceptibility to vasculitis including AAV, BD, and KD in Asians.

Susceptibility weighted imaging (SWI) of the kidney at 3 T. Initial results

International Nuclear Information System (INIS)

Mie, Moritz B.; Zoellner, Frank G.; Heilmann, Melanie; Schad, Lothar R.; Nissen, Johanna C.; Schoenberg, Stefan O.; Michaely, Henrik J.

2010-01-01

Susceptibility weighted imaging provides diagnostic information in strokes, hemorrhages, and cerebral tumors and has proven to be a valuable tool in imaging venous vessels in the cerebrum. The SWI principle is based on the weighting of T 2 * weighted magnitude images with a phase mask, therewith improving image contrast of veins or neighbouring structures of different susceptibility, in general. T 2 * weighted MRI is already used for assessment of kidney function. In this paper, the feasibility of SWI on kidneys was investigated. Translation of SWI from the brain to the kidneys comes along with two main challenges: (i) organ motion due to breathing and (ii) a higher oxygenation level of renal veins compared to the brain. To handle these problems, the acquisition time has been cut down to allow for breath-hold examinations, and different post-processing methods including a new phase mask were investigated to visualize renal veins. Results showed that by a new post-processing strategy SWI contrast was enhanced on average by a factor of 1.33 compared to the standard phase mask. In summary, initial experiences of SWI on the kidneys demonstrated the feasibility. However, further technical developments have to be performed to make this technology applicable in clinical abdominal MRI. (orig.)

Association of Genetic Susceptibility Variants for Type 2 Diabetes with Breast Cancer Risk in Women of European Ancestry

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Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K.; Milne, Roger L.; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E.; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V.; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G.; Guénel, Pascal; Haiman, Christopher A.; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J.; Hopper, John L.; Jakubowska, Anna; Jasmine, Farzana; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A.; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E.; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J.; Schmutzler, Rita K.; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C.; Swerdlow, Anthony J; Toland, Amanda E.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B.; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S.; Winqvist, Robert; Zamora, M. Pilar; Zhao, Hui; Dunning, Alison M.; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F.; Zheng, Wei

2016-01-01

Purpose Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. Methods We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (OR) and 95% confidence intervals (CI) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. Results The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at P < 0.001), rs9939609 (FTO) (OR = 0.94, 95% CI = 0.92 – 0.95, P = 4.13E-13), rs7903146 (TCF7L2) (OR = 1.04, 95% CI = 1.02 – 1.06, P = 1.26E-05), and rs8042680 (PRC1) (OR = 0.97, 95% CI = 0.95 – 0.99, P = 8.05E-04). Conclusions We have shown that several genetic risk variants were associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk. PMID:27053251

Genetic polymorphism of glutathion S-transferase P1 (GSTP1 Ile105Val and susceptibility to atherogenesis in patients with type 2 diabetes mellitus

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Grubiša Ivana

2013-01-01

Full Text Available One of the characteristics of type 2 diabetes mellitus (T2DM is the state of persistent oxidative stress (OS that has been implicated in the pathogenesis of diseases such is atherosclerosis mainly through chronic hyperglycemia that stimulates production of reactive oxygen species (ROS and increases OS. Glutathione S-transferase P1 (GSTP1 is a member of the cytosolic GST superfamily. It plays an important role in neutralizing OS as an enzyme. Also, it participates in regulation of stress signaling and protects cells against apoptosis via its noncatalytic ligand-binding activity. GSTP1 Ile105Val functional polymorphism influences protein catalytic activity and stability and the aim of this study was to determine whether this gene variation influences susceptibility to atherogenesis in T2DM patients. A total of 240 individuals (140 patients with T2DM, accompanied with clinical manifestations of atherosclerosis, and 100 healthy controls were included in this study. Genomic DNA was isolated from peripheral blood cells and genotyping was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP analysis. We obtained no statistically significant differences in the distribution of alleles and genotypes between cases and controls (P>0.05 but association between Ile/Val (OR=0.6, 95%CI=0.35-1.05, P=0.08 and Val/Val (OR=0.45, 95%CI=0.18-1.11, P=0.08 genotypes and disease approached significance (P=0.08. Our results indicated that a larger study group is needed to establish the true relationship between potentialiy protective allele Val and the disease, and to determine the influence of other GSTP1 polymorphisms on atherogenesis in T2DM patients. [Projekat Ministarstva nauke Republike Srbije, br. 175075

Signal alteration of the cochlear perilymph on 3 different sequences after intratympanic Gd-DTPA administration at 3 tesla. Comparison of 3D-FLAIR, 3D-T1-weighted imaging, and 3D-CISS

International Nuclear Information System (INIS)

Yamazaki, Masahiro; Naganawa, Shinji; Kawai, Hisashi; Nihashi, Takashi; Nakashima, Tsutomu

2010-01-01

Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) imaging after intratympanic gadolinium injection is useful for pathophysiologic and morphologic analysis of the inner ear. However, statistical analysis of differences in inner ear signal intensity among 3D-FLAIR and other sequences has not been reported. We evaluated the signal intensity of cochlear fluid on each of 3D-FLAIR, 3D-T 1 -weighted imaging (T 1 WI), and 3D-constructive interference in the steady state (CISS) to clarify the differences in contrast effect among these 3 sequences using intratympanic gadolinium injection. Twenty-one patients underwent 3D-FLAIR, 3D-T 1 WI, and 3D-CISS imaging at 3 tesla 24 hours after intratympanic injection of gadolinium. We determined regions of interest of the cochleae (C) and medulla oblongata (M) on each image, evaluated the signal intensity ratio between C and M (CM ratio), and determined the ratio of cochlear signal intensity of the injected side to that of the non-injected side (contrast value). The CM ratio of the injected side (3.00±1.31, range, 0.53 to 4.88, on 3D-FLAIR; 0.83±0.30, range, 0.36 to 1.58 on 3D-T 1 WI) was significantly higher than that of the non-injected side (0.52±0.14, range, 0.30 to 0.76 on 3D-FLAIR; 0.49±0.11, range, 0.30 to 0.71 on 3D-T 1 WI) on 3D-FLAIR and 3D-T 1 WI (P 1 WI (1.73±0.60 range, 0.98 to 3.09) (P<0.001). The 3D-FLAIR sequence is the most sensitive for observing alteration in inner ear fluid signal after intratympanic gadolinium injection. Our results warrant use of 3D-FLAIR as a sensitive imaging technique to clarify the pathological and morphological mechanisms of disorders of the inner ear. (author)

Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.

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Brittany V Martin-Murphy

Full Text Available Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD. Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d(-/- mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD feeding. Compared with their WT counterparts, CD1d(-/- mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d(-/- mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health.

Avoidant coping moderates the relationship between paternal involvement in the child's type 1 diabetes (T1D) care and parenting stress.

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Teasdale, Ashley; Limbers, Christine

2018-01-01

Fathers may experience greater parenting stress and anxiety when they are more involved in their child's type 1 diabetes (T1D) care. The present study evaluated whether seeking social support and avoidant coping strategies moderate the relationship between paternal involvement in the child's T1D care and parenting stress in an international sample. Two hundred forty-nine fathers of young children with T1D completed the Parenting Stress Index (PSI), Pediatric Inventory for Parents (PIP), Dads' Active Disease Support scale (DADS), COPE Inventory, Self-Care Inventory (SCI-R), and a demographic questionnaire online. Pearson's product moment correlations were computed, and multiple linear regression analysis was conducted with three separate models in which the PSI Child Domain, PIP Frequency, and PIP Difficulty scores represented different parenting stress outcomes. The interaction between use of denial coping and DADS Involvement was significantly correlated with general parenting stress ( p diabetes treatment regimen ( p management.

3D High Resolution l1-SPIRiT Reconstruction on Gadgetron based Cloud

DEFF Research Database (Denmark)

Xue, Hui; Kelmann, Peter; Inati, Souheil

framework to support distributed computing in a cloud environment. This extension is named GT-Plus. A cloud version of 3D l1-SPIRiT was implemented on the GT-Plus framework. We demonstrate that a 3mins reconstruction could be achieved for 1mm3 isotropic resolution neuro scans with significantly improved......Applying non-linear reconstruction to high resolution 3D MRI is challenging because of the lengthy computing time needed for those iterative algorithms. To achieve practical processing duration to enable clinical usage of non-linear reconstruction, we have extended previously published Gadgetron...

IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis.

Science.gov (United States)

Engelbertsen, Daniel; Rattik, Sara; Wigren, Maria; Vallejo, Jenifer; Marinkovic, Goran; Schiopu, Alexandru; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

2018-01-01

The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. We transferred apoe-/-myd88+/+ or apoe-/-myd88-/- CD4+ T cells to T- and B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88+/+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-γ. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Simultaneous influence of hydrostatic pressure and temperature on diamagnetic susceptibility of impurity doped quantum dots under the aegis of noise

International Nuclear Information System (INIS)

Saha, Surajit; Ganguly, Jayanta; Bera, Aindrila; Ghosh, Manas

2016-01-01

Highlights: • Diamagnetic susceptibility (DMS) of doped quantum dot is studied. • Hydrostatic pressure (HP) and temperature (T) affect DMS. • The dot is subjected to Gaussian white noise. • DMS also depends on mode of application of noise. - Abstract: We explore the diamagnetic susceptibility (DMS) of impurity doped quantum dot (QD) in presence of Gaussian white noise and under the combined influence of hydrostatic pressure (HP) and temperature (T). Presence of noise and also its mode of application discernibly affect the DMS profile. Application of HP and T invites greater delicacies in the observed DMS profiles. However, whereas the interplay between T and noise comes out to be extremely sensitive in fabricating the DMS profile, the pressure-noise interplay appears to be not that much noticeable. Under all conditions of temperature and pressure, the presence of multiplicative noise diminishes the value of DMS in comparison with that in presence of its additive analogue. The present study renders a deep insight into the remarkable role played by the interplay between noise, hydrostatic pressure and temperature in controlling the effective confinement imposed on the system which bears unquestionable relevance.

Simultaneous influence of hydrostatic pressure and temperature on diamagnetic susceptibility of impurity doped quantum dots under the aegis of noise

Energy Technology Data Exchange (ETDEWEB)

Saha, Surajit [Department of Chemistry, Physical Chemistry Section, Visva Bharati University, Santiniketan, Birbhum 731 235, West Bengal (India); Ganguly, Jayanta [Department of Chemistry, Brahmankhanda Basapara High School, Basapara, Birbhum 731215, West Bengal (India); Bera, Aindrila [Department of Chemistry, Physical Chemistry Section, Visva Bharati University, Santiniketan, Birbhum 731 235, West Bengal (India); Ghosh, Manas, E-mail: pcmg77@rediffmail.com [Department of Chemistry, Physical Chemistry Section, Visva Bharati University, Santiniketan, Birbhum 731 235, West Bengal (India)

2016-11-30

Highlights: • Diamagnetic susceptibility (DMS) of doped quantum dot is studied. • Hydrostatic pressure (HP) and temperature (T) affect DMS. • The dot is subjected to Gaussian white noise. • DMS also depends on mode of application of noise. - Abstract: We explore the diamagnetic susceptibility (DMS) of impurity doped quantum dot (QD) in presence of Gaussian white noise and under the combined influence of hydrostatic pressure (HP) and temperature (T). Presence of noise and also its mode of application discernibly affect the DMS profile. Application of HP and T invites greater delicacies in the observed DMS profiles. However, whereas the interplay between T and noise comes out to be extremely sensitive in fabricating the DMS profile, the pressure-noise interplay appears to be not that much noticeable. Under all conditions of temperature and pressure, the presence of multiplicative noise diminishes the value of DMS in comparison with that in presence of its additive analogue. The present study renders a deep insight into the remarkable role played by the interplay between noise, hydrostatic pressure and temperature in controlling the effective confinement imposed on the system which bears unquestionable relevance.

Regulation of 1,25-dihydroxyvitamin D, receptors by [3H]-1,25-dihydroxyvitamin D3 in cultured cells (T-47D): evidence for receptor upregulation

International Nuclear Information System (INIS)

Reinhardt, T.A.; Horst, R.L.

1986-01-01

The authors examined the effect of 1,25-(OH) 2 D 3 on receptor concentration in cultured cells (T-47D). Two days prior to experiment, cells were fed with RPMI 1640 + 10% serum and 24-32 hours prior to experiment the media was replaced with RPMI 1640 + 25 mM Hepes + 1% serum. [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess cold hormone was used to treat the cells. Occupied receptors were measured in freshly prepared cytosols. Total receptors were measured following a 16-hour incubation of cytosols in the presence of 0.6 nM [ 3 H]-1,25-(OH) 2 D 3 +/- 100-fold molar excess of cold hormone at 4 0 C. Treatment of cell cultures for 16-18 hours with 0.5-1.0 nM [ 3 H]-1,25-(OH) 2 D 3 resulted in a 30-40% receptor occupancy by the hormone and a 2- to 3-fold increase in total cell receptor as compared to vehicle-treated controls. Time course studies showed a rapid increase in total receptors up to 16 hours post-treatment in the face of declining receptor occupancy. Actinomycin D blocked the [ 3 H]-1,25-(OH) 2 D 3 -dependent rise in cell receptor. The physiological significance of this receptor upregulation is not known nor is it known whether upregulation results from synthesis of new receptors and/or is the result of the activation of preformed receptors by a inducible activator protein

Estimating Fitness by Competition Assays between Drug Susceptible and Resistant Mycobacterium tuberculosis of Predominant Lineages in Mumbai, India

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Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges

2012-01-01

Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407

Combined MRI and MRS in prostate cancer: improvement of spectral quality by susceptibility matching.

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Scheidler, J; Vogel, M; Gross, P; Heuck, A

2009-06-01

Local magnetic field inhomogeneity caused by susceptibility artifacts due to air in the endorectal coil substantially degrades the quality of 3D MR spectroscopic imaging (3D-MRSI). Perflubron (PFB) has magnetic susceptibility similar to that of human tissue. We prospectively assessed the effect of susceptibility matching using PFB on in vivo prostate (1)H-3D-MRSI. Ninety-one consecutive patients referred for 3D-MRSI were examined using air and PFB as the filling agent for endorectal coils at 1.5T with an identically placed PRESS box and sat bands. Solely auto-shim without additional manual shimming was used. The full width at half maximum (FWHM) of the water peak was statistically compared with a paired t-test. The spectral quality was visually evaluated for the definition of metabolite peaks and for the citrate peak split (duplet). The MR image quality was rated on a five-point scale. FWHM was significantly less (p PFB (mean 9.0 +/- 3.3, range 3 - 20) than air (mean 14.9 +/- 4.2, range 6 - 26) in 85/91 patients (93%). The spectral quality markedly improved using PFB and frequently the duplet of the citrate peak was able to be identified. Image quality ratings were similar (mean rating PFB 4.2, air 4.3 points). Omitting manual shimming led to a time savings of 4 min. per study. 3D-MRSI using PFB for susceptibility matching benefits from significantly better local field homogeneity, thus providing improved spectra quality. Combined with a substantial time savings in data acquisition, this may increase the clinical utilization of 3D-MRSI in patients with prostate cancer.

Susceptibility and Influence in Social Media Word-of-Mouth

DEFF Research Database (Denmark)

Claussen, Jörg; Engelstätter, Benjamin; Ward, Michael R.

Peer influence through word-of-mouth (WOM) plays an important role in many information systems but identification of causal effects is challenging. We identify causal WOM effects in the empirical setting of game adoption in a social network for gamers by exploiting differences in individuals...... and receiver side. We find that users with the most influence on others tend to be better gamers, have larger social networks, but spend less time playing. Interestingly, these are also the users who are least susceptible to WOM effects....

The Efficiency of Delone Coverings of the Canonical Tilings MATH {cal T}(*(A_4)) -> T^*(A4) and MATH {cal T}(*(D_6)) -> T^*(D6)

Science.gov (United States)

Papadopolos, Zorka; Kasner, Gerald

This chapter is devoted to the coverings of the two quasiperiodic canonical tilings MATH {cal T}(*(A_4)) -> T^*(A4) and MATH {cal T}(*(D_6)) equiv {cal T}(*(2F)) -> T^*(D6) T^*(2F), obtained by projection from the root lattices A4 and D6, respectively. In the first major part of this chapter, in Sect. 5.2, we shall introduce a Delone covering MATH {cal C}(s_{{cal) T}(*(A_4)}) -> C^sT^*(A4) of the 2-dimensional decagonal tiling MATH {cal T}(*(A_4)) -> T^*(A4). In the second major part of this chapter, Sect. 5.3, we summarize the results related to the Delone covering of the icosahedral tiling MATH {cal T}(*(D_6)) -> T^*(D6), MATH {cal C}_{{cal T}(*(D_6)}) -> CT^*(D6) and determine the zero-, single-, and double- deckings and the resulting thickness of the covering. In the conclusions section, we give some suggestions as to how the definition of the Delone covering might be changed in order to reach some real (full) covering of the icosahedral tiling MATH {cal T}(*(D_6)) -> T^*(D6). In Section 5.2 the definition of the Delone covering is also changed in order to avoid an unnecessary large thickness of the covering.

Feasibility of using automated insufflated carbon dioxide (CO2) for luminal distension in 3.0 T MR colonography

International Nuclear Information System (INIS)

Zijta, F.M.; Nederveen, A.J.; Jensch, S.; Florie, J.; Bipat, S.; Paardt, M.P. van der; Montauban van Swijndregt, A.D.; Stoker, J.

2012-01-01

Purpose: Primary aim of our study was to prospectively evaluate the feasibility of automated carbon dioxide (CO 2 ) delivery as luminal distending agent in 3.0 T MR colonography. Materials and methods: Rectally insufflated CO 2 was evaluated in four groups with different bowel preparation (A–D). Bowel preparation regimes were: gadolinium-based tagging (A), bowel purgation (B), barium-based tagging (C) and iodine-based tagging (D). Supine (3D)T1w-FFE and (2D)T2w-SSFSE series were acquired. Each colon was divided into six segments (cecum S1–rectum S6). Two observers independently assessed the presence of artefacts, diagnostic confidence and segmental colonic distension. Also characteristics of the residual stool (presence, composition and signal-intensity) were assessed per segment. Discomfort was assessed with questionnaires. Results: Fourteen healthy subjects were included. Colonic distension by means of rectally insufflated CO 2 was not associated with susceptibility artefacts. Overall image quality was affected by the presence of bowel motion-related artefacts: none of the segments in 3DT1w-series and 10/84 (12%) colon segments in 2DT2w-series were rated artefact-free by both observers. Diagnostic confidence ratings were superior for the 2DT2w-SSFSE series. Overall bowel distension was rated adequate to optimal in 312/336 (93%) colon segments. Conclusion: MR colonography at 3.0 T using carbon dioxide (CO 2 ) for colonic distension is technically feasible. The presence of intraluminal CO 2 did not result in susceptibility artefacts, although overall image quality was influenced by artefacts.

Characterization of TRZ1, a yeast homolog of the human candidate prostate cancer susceptibility gene ELAC2 encoding tRNase Z

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Chen Yuan

2005-05-01

Full Text Available Abstract Background In humans, mutation of ELAC2 is associated with an increased risk of prostate cancer. ELAC2 has been shown to have tRNase Z activity and is associated with the γ-tubulin complex. Results In this work, we show that the yeast homolog of ELAC2, encoded by TRZ1 (tRNase Z 1, is involved genetically in RNA processing. The temperature sensitivity of a trz1 mutant can be rescued by multiple copies of REX2, which encodes a protein with RNA 3' processing activity, suggesting a role of Trz1p in RNA processing in vivo. Trz1p has two putative nucleotide triphosphate-binding motifs (P-loop and a conserved histidine motif. The histidine motif and the putative nucleotide binding motif at the C-domain are important for Trz1p function because mutant proteins bearing changes to the critical residues in these motifs are unable to rescue deletion of TRZ1. The growth defect exhibited by trz1 yeast is not complemented by the heterologous ELAC2, suggesting that Trz1p may have additional functions in yeast. Conclusion Our results provide genetic evidence that prostate cancer susceptibility gene ELAC2 may be involved in RNA processing, especially rRNA processing and mitochondrial function.

Incidence and prevalence of diabetic ketoacidosis (DKA) among adults with type 1 diabetes mellitus (T1D): a systematic literature review.

Science.gov (United States)

Fazeli Farsani, Soulmaz; Brodovicz, Kimberly; Soleymanlou, Nima; Marquard, Jan; Wissinger, Erika; Maiese, Brett A

2017-08-01

To summarise incidence and prevalence of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D) for the overall patient population and different subgroups (age, sex, geographical region, ethnicity and type of insulin administration). Systematic literature review (SLR). Medline (via PubMed) and Embase (1 January 2000 to 23 June 2016). Peer-reviewed observational studies with reported data on the incidence or prevalence of DKA in T1D adults were included. A single reviewer completed the study screening and selection process and a second reviewer performed an additional screening of approximately 20% of the publications; two reviewers independently conducted the quality assessment; the results were narratively synthesised. Out of 1082 articles, 19 met the inclusion and exclusion criteria, with two additional studies identified that did not specify the patient age range and are therefore not included in the SLR. Overall, eight studies reported incidence with a range of 0-56 per 1000 person-years (PYs), with one outlying study reporting an incidence of 263 per 1000 PYs. Eleven studies reported prevalence with a range of 0-128 per 1000 people. Prevalence of DKA decreased with increasing age. Subgroup analyses were performed using data from no more than two studies per subgroup. There was a higher prevalence of DKA reported in women, non-whites and patients treated with insulin injections compared with men, whites and patients using continuous subcutaneous insulin infusion pumps, respectively. To our knowledge, this is the first SLR on the epidemiology of DKA in T1D adults. Despite an increasing prevalence of T1D in recent years, DKA in adults has been poorly characterised. In an era when the benefit-risk profiles of new antidiabetic therapies are being evaluated, including the potential risk of DKA, there is a clear need to better elucidate the expected rate of DKA among T1D adults. © Article author(s) (or their employer(s) unless otherwise stated in the text

Inherited susceptibility to cancer and other factors influencing occurrence of cancer

International Nuclear Information System (INIS)

Pawlak, A.L.

1994-01-01

The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs

Effects of GWAS-associated genetic variants on lncRNAs within IBD and T1D candidate loci

DEFF Research Database (Denmark)

Mirza, Aashiq H; Kaur, Simranjeet; Brorsson, Caroline A

2014-01-01

-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here......, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs...... within and in close proximity (+/-5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable...

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis

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M. Costagli

2016-01-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1 in patients with upper motor neuron (UMN impairment is pronouncedly hypointense in Magnetic Resonance (MR T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM. Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

A TagSNP in SIRT1 gene confers susceptibility to myocardial infarction in a Chinese Han population.

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Jie Cheng

Full Text Available SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720 in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR of 1.57 [95% confidence interval (CI = 1.15-2.16, Bonferroni corrected P (Pc = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14-2.35, Pc = 0.021 compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old. Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09-1.84, Pc = 0.040. However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.

Time-resolved 3D pulmonary perfusion MRI: comparison of different k-space acquisition strategies at 1.5 and 3 T.

Science.gov (United States)

Attenberger, Ulrike I; Ingrisch, Michael; Dietrich, Olaf; Herrmann, Karin; Nikolaou, Konstantin; Reiser, Maximilian F; Schönberg, Stefan O; Fink, Christian

2009-09-01

Time-resolved pulmonary perfusion MRI requires both high temporal and spatial resolution, which can be achieved by using several nonconventional k-space acquisition techniques. The aim of this study is to compare the image quality of time-resolved 3D pulmonary perfusion MRI with different k-space acquisition techniques in healthy volunteers at 1.5 and 3 T. Ten healthy volunteers underwent contrast-enhanced time-resolved 3D pulmonary MRI on 1.5 and 3 T using the following k-space acquisition techniques: (a) generalized autocalibrating partial parallel acquisition (GRAPPA) with an internal acquisition of reference lines (IRS), (b) GRAPPA with a single "external" acquisition of reference lines (ERS) before the measurement, and (c) a combination of GRAPPA with an internal acquisition of reference lines and view sharing (VS). The spatial resolution was kept constant at both field strengths to exclusively evaluate the influences of the temporal resolution achieved with the different k-space sampling techniques on image quality. The temporal resolutions were 2.11 seconds IRS, 1.31 seconds ERS, and 1.07 VS at 1.5 T and 2.04 seconds IRS, 1.30 seconds ERS, and 1.19 seconds VS at 3 T.Image quality was rated by 2 independent radiologists with regard to signal intensity, perfusion homogeneity, artifacts (eg, wrap around, noise), and visualization of pulmonary vessels using a 3 point scale (1 = nondiagnostic, 2 = moderate, 3 = good). Furthermore, the signal-to-noise ratio in the lungs was assessed. At 1.5 T the lowest image quality (sum score: 154) was observed for the ERS technique and the highest quality for the VS technique (sum score: 201). In contrast, at 3 T images acquired with VS were hampered by strong artifacts and image quality was rated significantly inferior (sum score: 137) compared with IRS (sum score: 180) and ERS (sum score: 174). Comparing 1.5 and 3 T, in particular the overall rating of the IRS technique (sum score: 180) was very similar at both field

First Comprehensive In Silico Analysis of the Functional and Structural Consequences of SNPs in Human GalNAc-T1 Gene

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Hussein Sheikh Ali Mohamoud

2014-01-01

Full Text Available GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568 were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.

Padé approximations for the magnetic susceptibilities of Heisenberg antiferromagnetic spin chains for various spin values

International Nuclear Information System (INIS)

Law, J M; Benner, H; Kremer, R K

2013-01-01

The temperature dependence of the spin susceptibilities of S = 1, 3/2 , 2, 5/2 and 7/2 Heisenberg antiferromagnetic 1D spins chains with nearest-neighbor coupling was simulated via quantum Monte Carlo calculations, within the reduced temperature range of 0.005 ≤ T* ≤ 100, and fitted to a Padé approximation with deviations between the simulated and fitted data of the same order of magnitude as or smaller than the quantum Monte Carlo simulation error. To demonstrate the practicality of our theoretical findings, we compare these results with the susceptibility of the well known 1D chain compound TMMC ([(CH 3 ) 4 N[MnCl 3

Genes affecting β-cell function in type 1 diabetes

DEFF Research Database (Denmark)

Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

2015-01-01

Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

Tokamak Fusion Test Reactor D-T results

International Nuclear Information System (INIS)

Meade, D.M.

1995-01-01

Temperatures, densities and confinement of deuterium plasmas confined in tokamaks have been achieved within the last decade that are approaching those required for a D-T reactor. As a result, the unique phenomena present in a D-T reactor plasma (D-T plasma confinement, α confinement, α heating and possible α-driven instabilities) can now be studied in the laboratory. Recent experiments on the Tokamak Fusion Test Reactor (TFTR) have been the first magnetic fusion experiments to study plasmas with reactor fuel concentrations of tritium. The injection of about 20MW of tritium and 14MW of deuterium neutral beams into the TFTR produced a plasma with a T-to-D density ratio of about 1 and yielding a maximum fusion power of about 9.2MW. The fusion power density in the core of the plasma was about 1.8MWm -3 , approximating that expected in a D-T fusion reactor. A TFTR plasma with a T-to-D density ratio of about 1 was found to have about 20% higher energy confinement time than a comparable D plasma, indicating a confinement scaling with average ion mass A of τ E ∝A 0.6 . The core ion temperature increased from 30 to 37keV owing to a 35% improvement of ion thermal conductivity. Using the electron thermal conductivity from a comparable deuterium plasma, about 50% of the electron temperature increase from 9 to 10.6keV can be attributed to electron heating by the α particles. The approximately 5% loss of α particles, as observed on detectors near the bottom edge of the plasma, was consistent with classical first orbit loss without anomalous effects. Initial measurements have been made of the confined high energy α particles and the resultant α ash density. At fusion power levels of 7.5MW, fluctuations at the toroidal Alfven eigen-mode frequency were observed by the fluctuation diagnostics. However, no additional α loss due to the fluctuations was observed. (orig.)

The scientific case for a JET D-T experiment

International Nuclear Information System (INIS)

Weisen, H.; Sips, A. C. C.; Horton, L. D.; Challis, C. D.; Sharapov, S. E.; Zastrow, K.-D.; Eriksson, L.-G.; Batistoni, P.

2014-01-01

After the first high power D-T experiment in JET in 1997 (DTE1), when JET was equipped with Carbon PFC's, a proposed second high power (up to ∼40MW) D-T campaign (DTE2) in the current Be/W vessel will address essential operational, technical, diagnostics and scientific issues in support of ITER. These experiments are proposed to minimize the risks to ITER by testing strategies for the management of the in-vessel tritium content, by providing the basis for transferring operational scenarios from non-active operation to D-T mixtures and by addressing the issue of the neutron measurement accuracy. Dedicated campaigns with operation in Deuterium, Hydrogen and Tritium before the D-T campaign proper will allow the investigation of isotope scaling of the H-mode transition, pedestal physics, heat, particle, momentum and impurity transport in much greater detail than was possible in DTE1. The D-T campaign proper will include validations of the baseline ELMy H-Mode scenario, of the hybrid H-mode and advanced tokamak scenarios, as well as the investigation of alpha particle physics and the qualification of ICRH scenarios suitable for D-T operation. This paper reviews the scientific goals of DTE2 together with a summary of the results of DTE1

The diabetes type 1 locus Idd6 modulates activity of CD4+CD25+ regulatory T-cells.

Science.gov (United States)

Rogner, Ute Christine; Lepault, Françoise; Gagnerault, Marie-Claude; Vallois, David; Morin, Joëlle; Avner, Philip; Boitard, Christian

2006-01-01

The genetic locus Idd6 confers susceptibility to the spontaneous development of type 1 diabetes in the NOD mouse. Our studies on disease resistance of the congenic mouse strain NOD.C3H 6.VIII showed that Idd6 influences T-cell activities in the peripheral immune system and suggest that a major mechanism by which the Idd6 locus modifies diabetes development is via modulation of regulatory T-cell activities. Our transfer experiments using total splenocytes and purified T-cells demonstrated that the locus specifically controls the efficiency of disease protection mediated by the regulatory CD4(+)CD25(+) T-cell subset. Our data also implicate the Idd6 locus in controlling the balance between infiltrating lymphocytes and antigen-presenting cells within the pancreatic islet.

Correlates of susceptibility to smoking among Mexican origin youth residing in Houston, Texas: A cross-sectional analysis

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Prokhorov Alexander V

2008-09-01

Full Text Available Abstract Background Survey data suggest that in Texas Latino youth exhibit higher rates of susceptibility to smoking than youth from other ethnic groups. In this analysis we examined the relationship between susceptibility to smoking and well-known risk factors associated with smoking initiation among a cohort of 11 to 13 year old Mexican origin youth residing in Houston, Texas. Methods We analyzed cross-sectional survey data from 1,187 participants who reported they had never smoked, even a puff of a cigarette. The survey assessed peer and family social influence, school and neighborhood characteristics, level of family acculturation and socioeconomic status, and attitudes toward smoking. Bivariate associations, Student's t-tests, and logistic regression analysis were used to examine predictors of susceptibility. Results Overall, 22.1% of the never-smokers were susceptible to smoking. Boys were more likely to be susceptible than girls (25.6% vs. 18.9%, and susceptible children were slightly older than non-susceptible children (12.1 vs. 11.8 years. In addition, multivariate analyses revealed that positive expectations about smoking exerted the strongest influence on susceptibility status (odds ratio = 4.85. Multivariate analyses further revealed that compared to non-susceptible participants, susceptibles were more likely to report peer influences supportive of smoking, lower subjective social status and more detentions at school, more temptations to try smoking and to have a mother and a brother who smokes. Conclusion Our findings suggest that interventions that target positive expectations about smoking may be useful in this population. Furthermore, because youth encounter smoking-initiation risk factors in different social environments, our results underscore the continued need for both family- and school-based primary prevention programs to adequately combat their influence. The results also can be used to inform the development of culturally

Neural responses to exclusion predict susceptibility to social influence.

Science.gov (United States)

Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

2014-05-01

Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

Birth Order and Susceptibility to Peer Modeling Influences in Young Boys

Science.gov (United States)

Finley, Gordon E.; Cheyne, James A.

1976-01-01

Susceptibility to peer modeling influences as a function of birth order was studied by examining the data of 390 boys from kindergarten through third grade who previously had participated in moral transgression experiments. (MS)

Comparison of contrast-enhanced T1-weighted and 3D constructive interference in steady state images for predicting outcome after hearing-preservation surgery for vestibular schwannoma

Energy Technology Data Exchange (ETDEWEB)

Kocaoglu, M.; Bulakbasi, N.; Ucoz, T.; Ustunsoz, B.; Tayfun, C.; Somuncu, I. [GATA Department of Radiology, 06018, Etlik, Ankara (Turkey); Pabuscu, Y. [Department of Radiology, Celal Bayar University, Manisa (Turkey)

2003-07-01

We compared contrast-enhanced T1-weighted and 3D constructive interference in steady state (CISS) sequences for demonstrating possible prognostic factors in hearing-preservation surgery for vestibular schwannoma. We studied 22 patients with vestibular schwannomas having hearing-preservation surgery. Postoperatively six (27%) had a facial palsy and eight (36%) had hearing loss. There was a significant correlation between the size of the tumour and facial palsy (r=-0.72). Both techniques adequately demonstrated all tumours. Involvement of the fundus of the internal auditory canal (IAC) and a small distance between the lateral border of the tumour and the fundus were correlated significantly with hearing loss (r=-0.81 and -0.75, respectively). The 3D-CISS sequence, by virtue of its high contrast resolution was superior to T1-weighted images (P<0.05) for detection of the fundal involvement. The direction of displacement of the facial nerve did not correlate with facial palsy or hearing loss. We think that 3D-CISS images better show the features influencing surgical outcome, but that contrast-enhanced T1-weighted images are required for diagnosis. (orig.)

Comparison of contrast-enhanced T1-weighted and 3D constructive interference in steady state images for predicting outcome after hearing-preservation surgery for vestibular schwannoma

International Nuclear Information System (INIS)

Kocaoglu, M.; Bulakbasi, N.; Ucoz, T.; Ustunsoz, B.; Tayfun, C.; Somuncu, I.; Pabuscu, Y.

2003-01-01

We compared contrast-enhanced T1-weighted and 3D constructive interference in steady state (CISS) sequences for demonstrating possible prognostic factors in hearing-preservation surgery for vestibular schwannoma. We studied 22 patients with vestibular schwannomas having hearing-preservation surgery. Postoperatively six (27%) had a facial palsy and eight (36%) had hearing loss. There was a significant correlation between the size of the tumour and facial palsy (r=-0.72). Both techniques adequately demonstrated all tumours. Involvement of the fundus of the internal auditory canal (IAC) and a small distance between the lateral border of the tumour and the fundus were correlated significantly with hearing loss (r=-0.81 and -0.75, respectively). The 3D-CISS sequence, by virtue of its high contrast resolution was superior to T1-weighted images (P<0.05) for detection of the fundal involvement. The direction of displacement of the facial nerve did not correlate with facial palsy or hearing loss. We think that 3D-CISS images better show the features influencing surgical outcome, but that contrast-enhanced T1-weighted images are required for diagnosis. (orig.)

Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis

DEFF Research Database (Denmark)

Størling, Joachim; Pociot, Flemming

2017-01-01

(GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D...... susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes...

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

Science.gov (United States)

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

MR Imaging of the Internal Auditory Canal and Inner Ear at 3T: Comparison between 3D Driven Equilibrium and 3D Balanced Fast Field Echo Sequences

Energy Technology Data Exchange (ETDEWEB)

Byun, Jun Soo; Kim, Hyung Jin; Yim, Yoo Jeong; Kim, Sung Tae; Jeon, Pyoung; Kim, Keon Ha [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sam Soo; Jeon, Yong Hwan; Lee, Ji Won [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of)

2008-06-15

To compare the use of 3D driven equilibrium (DRIVE) imaging with 3D balanced fast field echo (bFFE) imaging in the assessment of the anatomic structures of the internal auditory canal (IAC) and inner ear at 3 Tesla (T). Thirty ears of 15 subjects (7 men and 8 women; age range, 22 71 years; average age, 50 years) without evidence of ear problems were examined on a whole-body 3T MR scanner with both 3D DRIVE and 3D bFFE sequences by using an 8-channel sensitivity encoding (SENSE) head coil. Two neuroradiologists reviewed both MR images with particular attention to the visibility of the anatomic structures, including four branches of the cranial nerves within the IAC, anatomic structures of the cochlea, vestibule, and three semicircular canals. Although both techniques provided images of relatively good quality, the 3D DRIVE sequence was somewhat superior to the 3D bFFE sequence. The discrepancies were more prominent for the basal turn of the cochlea, vestibule, and all semicircular canals, and were thought to be attributed to the presence of greater magnetic susceptibility artifacts inherent to gradient-echo techniques such as bFFE. Because of higher image quality and less susceptibility artifacts, we highly recommend the employment of 3D DRIVE imaging as the MR imaging choice for the IAC and inner ear

Temperament Alters Susceptibility to Negative Peer Influence in Early Adolescence

Science.gov (United States)

Mrug, Sylvie; Madan, Anjana; Windle, Michael

2012-01-01

The role of deviant peers in adolescent antisocial behavior has been well documented, but less is known about individual differences in susceptibility to negative peer influence. This study examined whether specific temperament dimensions moderate the prospective relationship between peer deviance and delinquent behavior in early adolescence.…

Reactive Oxygen Species and Their Implications on CD4+ T Cells in Type 1 Diabetes.

Science.gov (United States)

Previte, Dana M; Piganelli, Jon D

2017-11-28

Previous work has indicated that type 1 diabetes (T1D) pathology is highly driven by reactive oxygen species (ROS). One way in which ROS shape the autoimmune response demonstrated in T1D is by promoting CD4 + T cell activation and differentiation. As CD4 + T cells are a significant contributor to pancreatic β cell destruction in T1D, understanding how ROS impact their development, activation, and differentiation is critical. Recent Advances: CD4 + T cells themselves generate ROS via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and electron transport chain activity. Moreover, T cells can also be exposed to exogenous ROS generated by other immune cells (e.g., macrophages and dendritic cells) and β cells. Genetically modified animals and ROS inhibitors have demonstrated that ROS blockade during activation results in CD4 + T cell hyporesponsiveness and reduced diabetes incidence. Critical Issues and Future Directions: Although the majority of studies with regard to T1D and CD4 + T cells have been done to examine the influence of redox on CD4 + T cell activation, this is not the only circumstance in which a T cell can be impacted by redox. ROS and redox have also been shown to play roles in CD4 + T cell-related tolerogenic mechanisms, including thymic selection and regulatory T cell-mediated suppression. However, the effect of these mechanisms with respect to T1D pathogenesis remains elusive. Therefore, pursuing these avenues may provide valuable insight into the global role of ROS and redox in autoreactive CD4 + T cell formation and function. Antioxid. Redox Signal. 00, 000-000.

T-CELL RESPONSES TO SYNTHETIC PEPTIDES OF HERPES-SIMPLEX VIRUS TYPE-1 GLYCOPROTEIN-D IN NATURALLY INFECTED INDIVIDUALS

NARCIS (Netherlands)

DAMHOF, RA; DRIJFHOUT, JW; SCHEFFER, AJ; WILTERDINK, JB; WELLING, GW; WELLINGWESTER, S

1993-01-01

To locate T cell determinants of glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1), proliferation assays of lymphocytes obtained from 10 healthy HSV-seropositive individuals were performed using 34 overlapping gD peptides as antigens. Despite large differences between individual responses

Requirements for charged-particle reaction cross sections in the d-d, d-t, t-t, and d-3He fuel cycles

International Nuclear Information System (INIS)

Jarmie, N.

1986-12-01

This paper reviews the status of experimental data and data evaluations for charged-particle reactions of interest in fusion-reactor design. In particular, the 2 H(t,α)n, 2 H(d,p) 3 H, 2 H(d, 3 He)n, 3 H(t,α)nn and 3 He(d,p) 4 He reactions at low energies are studied. Other secondary reactions are considered. The conclusion is that such cross sections are well known for the near and medium term, and that no crucial experimental lack exists. There is a serious lack of standard evaluations of these reactions, which should be in an internationally acceptable format and easily accessible. Support for generating such evaluations should be given serious consideration

Iron and Non-Iron-Related Characteristics of Multiple Sclerosis and Neuromyelitis Optica Lesions at 7T MRI.

Science.gov (United States)

Chawla, S; Kister, I; Wuerfel, J; Brisset, J-C; Liu, S; Sinnecker, T; Dusek, P; Haacke, E M; Paul, F; Ge, Y

2016-07-01

Characterization of iron deposition associated with demyelinating lesions of multiple sclerosis and neuromyelitis optica has not been well studied. Our aim was to investigate the potential of ultra-high-field MR imaging to distinguish MS from neuromyelitis optica and to characterize tissue injury associated with iron pathology within lesions. Twenty-one patients with MS and 21 patients with neuromyelitis optica underwent 7T high-resolution 2D-gradient-echo-T2* and 3D-susceptibility-weighted imaging. An in-house-developed algorithm was used to reconstruct quantitative susceptibility mapping from SWI. Lesions were classified as "iron-laden" if they demonstrated hypointensity on gradient-echo-T2*-weighted images and/or SWI and hyperintensity on quantitative susceptibility mapping. Lesions were considered "non-iron-laden" if they were hyperintense on gradient-echo-T2* and isointense or hyperintense on quantitative susceptibility mapping. Of 21 patients with MS, 19 (90.5%) demonstrated at least 1 quantitative susceptibility mapping-hyperintense lesion, and 11/21 (52.4%) had iron-laden lesions. No quantitative susceptibility mapping-hyperintense or iron-laden lesions were observed in any patients with neuromyelitis optica. Iron-laden and non-iron-laden lesions could each be further characterized into 2 distinct patterns based on lesion signal and morphology on gradient-echo-T2*/SWI and quantitative susceptibility mapping. In MS, most lesions (n = 262, 75.9% of all lesions) were hyperintense on gradient-echo T2* and isointense on quantitative susceptibility mapping (pattern A), while a small minority (n = 26, 7.5% of all lesions) were hyperintense on both gradient-echo-T2* and quantitative susceptibility mapping (pattern B). Iron-laden lesions (n = 57, 16.5% of all lesions) were further classified as nodular (n = 22, 6.4%, pattern C) or ringlike (n = 35, 10.1%, pattern D). Ultra-high-field MR imaging may be useful in distinguishing MS from neuromyelitis optica. Different

Islet-specific T cell clones transfer diabetes to nonobese diabetic (NOD) F1 mice.

Science.gov (United States)

Peterson, J D; Pike, B; McDuffie, M; Haskins, K

1994-09-15

To investigate diabetes resistance to T cell-mediated disease transfer, we administered islet-specific T cell clones to the F1 progeny of nonobese diabetic (NOD) mice that were crossed with various nondiabetes-prone inbred mouse strains. We investigated four diabetogenic CD4+ T cell clones and all induced insulitis and full development of diabetes in (SWR x NOD)F1, (SJL x NOD)F1, and (C57BL/6 x NOD)F1 mice. In contrast, (BALB/c x NOD)F1 and (CBA x NOD)F1 mice were susceptible to disease transfer by some T cell clones but not others, and (C57/L x NOD)F1 mice seemed to be resistant to both insulitis and disease transfer by all of the clones tested. Disease induced by the T cell clones in susceptible F1 strains was age dependent and could only be observed in recipients younger than 13 days old. Full or partial disease resistance did not correlate with the presence or absence of I-E, different levels of Ag expression in islet cells, or differences in APC function. The results from this study suggest that there may be multiple factors contributing to susceptibility of F1 mice to T cell clone-mediated induction of diabetes, including non-MHC-related genetic background, the immunologic maturity of the recipient, and individual characteristics of the T cell clones.

pH of Drinking Water Influences the Composition of Gut Microbiome and Type 1 Diabetes Incidence

Science.gov (United States)

Sofi, M. Hanief; Gudi, Radhika; Karumuthil-Melethil, Subha; Perez, Nicolas; Johnson, Benjamin M.; Vasu, Chenthamarakshan

2014-01-01

Nonobese diabetic (NOD) mice spontaneously develop type 1 diabetes (T1D), progression of which is similar to that in humans, and therefore are widely used as a model for understanding the immunological basis of this disease. The incidence of T1D in NOD mice is influenced by the degree of cleanliness of the mouse colony and the gut microflora. In this report, we show that the T1D incidence and rate of disease progression are profoundly influenced by the pH of drinking water, which also affects the composition and diversity of commensal bacteria in the gut. Female NOD mice that were maintained on acidic pH water (AW) developed insulitis and hyperglycemia rapidly compared with those on neutral pH water (NW). Interestingly, forced dysbiosis by segmented filamentous bacteria (SFB)-positive fecal transfer significantly suppressed the insulitis and T1D incidence in mice that were on AW but not in those on NW. The 16S rDNA–targeted pyrosequencing revealed a significant change in the composition and diversity of gut flora when the pH of drinking water was altered. Importantly, autoantigen-specific T-cell frequencies in the periphery and proinflammatory cytokine response in the intestinal mucosa are significantly higher in AW-recipient mice compared with their NW counterparts. These observations suggest that pH of drinking water affects the composition of gut microflora, leading to an altered autoimmune response and T1D incidence in NOD mice. PMID:24194504

Fine tuning a well-oiled machine: Influence of NK1.1 and NKG2D on NKT cell development and function.

Science.gov (United States)

Joshi, Sunil K; Lang, Mark L

2013-10-01

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but nonetheless expressed by NKT cells. These include several activating and inhibitory receptors that may fine-tune NKT development and survival, as well as activation via antigen receptors. Herein, we review the possible roles of the NK1.1 and NKG2D receptors in regulating development and function of NKT cells in health and disease. We suggest that pharmacological alteration of NKT activity should consider the potential complexities commensurate with NK1.1 and NKG2D expression. Published by Elsevier B.V.

CYP1A1, CYP3A5 and CYP3A7 polymorphisms and testicular cancer susceptibility.

Science.gov (United States)

Kristiansen, W; Haugen, T B; Witczak, O; Andersen, J M; Fosså, S D; Aschim, E L

2011-02-01

Testicular cancer (TC) incidence is increasing worldwide, but the aetiology remains largely unknown. An unbalanced level of oestrogens and androgens in utero is hypothesized to influence TC risk. Polymorphisms in genes encoding cytochrome P450 (CYP) enzymes involved in metabolism of reproductive hormones, such as CYP1A1, CYP3A5 and CYP3A7, may contribute to variability of an individual's susceptibility to TC. The aim of this case-control study was to investigate possible associations between different CYP genotypes and TC, as well as histological type of TC. The study comprised 652 TC cases and 199 controls of Norwegian Caucasian origin. Genotyping of the CYP1A1*2A (MspI), CYP1A1*2C (I462V), CYP1A1*4 (T461N), CYP3A5*3C (A6986G) and CYP3A7*2 (T409R) polymorphisms was performed using TaqMan allelic discrimination or sequencing. The CYP1A1*2A allele was associated with 44% reduced risk of TC with each polymorphic allele [odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.40-0.78, p(trend) = 0.001], whereas the CYP1A1*2C allele was associated with 56% reduced risk of TC with each polymorphic allele (OR = 0.44, 95% CI = 0.25-0.75, p(trend) = 0.003). The decreased risk per allele was significant for seminomas (OR = 0.46, 95% CI, 0.31-0.70, p(trend) < 0.001 and OR = 0.31, 95% CI = 0.14-0.66, p(trend) = 0.002, respectively), but only borderline significant for non-seminomas (OR = 0.65, 95% CI = 0.45-0.95, p(trend) = 0.027 and OR = 0.55, 95% CI = 0.30-1.01, p(trend) = 0.052, respectively). There were no statistically significant differences in the distribution of the CYP3A5*3C and CYP3A7*2 polymorphic alleles between TC cases and controls. This study suggests that polymorphisms in the CYP1A1 gene may contribute to variability of individual susceptibility to TC. © 2010 The Authors. International Journal of Andrology © 2010 European Academy of Andrology.

Friends' drinking norms and male adolescents' alcohol consumption: The moderating role of performance-based peer influence susceptibility.

Science.gov (United States)

Teunissen, Hanneke A; Kuntsche, Emmanuel; Scholte, Ron H J; Spijkerman, Renske; Prinstein, Mitchell J; Engels, Rutger C M E

2016-12-01

This study examined whether the relationship between friends' drinking norms and male adolescents' alcohol use is moderated by performance-based peer influence susceptibility. Seventy-three male adolescents (M = 17 years) from three schools in the Netherlands were exposed to the drinking norms of "peers" (electronic confederates) in a chat room experiment. These peers were either popular or unpopular, and conveyed pro- or anti-alcohol norms. Peer influence susceptibility was defined as the change in adolescents' answers before and after exposure to the peer norms. Multilevel regression analyses indicated that the relationship between friends' drinking norms and adolescents' alcohol use (assessed during eight weekends) was moderated by susceptibility to the pro-alcohol norms of popular peers. This relationship was stronger for adolescents who were highly susceptible. These findings suggest that a behavioral measure of peer influence susceptibility could be useful in alcohol prevention programs to select adolescents at risk for negative peer socialization. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. All rights reserved.

Fast CSF MRI for brain segmentation; Cross-validation by comparison with 3D T1-based brain segmentation methods.

Science.gov (United States)

van der Kleij, Lisa A; de Bresser, Jeroen; Hendrikse, Jeroen; Siero, Jeroen C W; Petersen, Esben T; De Vis, Jill B

2018-01-01

In previous work we have developed a fast sequence that focusses on cerebrospinal fluid (CSF) based on the long T2 of CSF. By processing the data obtained with this CSF MRI sequence, brain parenchymal volume (BPV) and intracranial volume (ICV) can be automatically obtained. The aim of this study was to assess the precision of the BPV and ICV measurements of the CSF MRI sequence and to validate the CSF MRI sequence by comparison with 3D T1-based brain segmentation methods. Ten healthy volunteers (2 females; median age 28 years) were scanned (3T MRI) twice with repositioning in between. The scan protocol consisted of a low resolution (LR) CSF sequence (0:57min), a high resolution (HR) CSF sequence (3:21min) and a 3D T1-weighted sequence (6:47min). Data of the HR 3D-T1-weighted images were downsampled to obtain LR T1-weighted images (reconstructed imaging time: 1:59 min). Data of the CSF MRI sequences was automatically segmented using in-house software. The 3D T1-weighted images were segmented using FSL (5.0), SPM12 and FreeSurfer (5.3.0). The mean absolute differences for BPV and ICV between the first and second scan for CSF LR (BPV/ICV: 12±9/7±4cc) and CSF HR (5±5/4±2cc) were comparable to FSL HR (9±11/19±23cc), FSL LR (7±4, 6±5cc), FreeSurfer HR (5±3/14±8cc), FreeSurfer LR (9±8, 12±10cc), and SPM HR (5±3/4±7cc), and SPM LR (5±4, 5±3cc). The correlation between the measured volumes of the CSF sequences and that measured by FSL, FreeSurfer and SPM HR and LR was very good (all Pearson's correlation coefficients >0.83, R2 .67-.97). The results from the downsampled data and the high-resolution data were similar. Both CSF MRI sequences have a precision comparable to, and a very good correlation with established 3D T1-based automated segmentations methods for the segmentation of BPV and ICV. However, the short imaging time of the fast CSF MRI sequence is superior to the 3D T1 sequence on which segmentation with established methods is performed.

Ion cyclotron heating of JET D-D and D-T optimised shear plasmas

International Nuclear Information System (INIS)

Cottrell, G.; Baranov, Y.; Bartlett, D.

1998-12-01

This paper discusses the unique roles played by Ion Cyclotron Resonance Heating (ICRH) in the preparation, formation and sustainment of internal transport barriers (ITBs) in high fusion performance JET optimised shear experiments using the Mk. H poloidal divertor. Together with Lower Hybrid Current Drive (LHCD), low power ICRH is applied during the early ramp-up phase of the plasma current, 'freezing in' a hollow or flat current density profile with q(0)>1. In combination with up to ∼ 20 MW of Neutral Beam Injection (NBI), the ICRH power is stepped up to ∼ 6 MW during the main low confinement (L-mode) heating phase. An ITB forms promptly after the power step, revealed by a region of reduced central energy transport and peaked profiles, with the ion thermal diffusivity falling to values close to the standard neo-classical level near the centre of both D-D and D-T plasmas. At the critical time of ITB formation, the plasma contains an energetic ICRF hydrogen minority ion population, contributing ∼ 50% to the total plasma pressure and heating mainly electrons. As both the NBI population and the thermal ion pressure develop, a substantial part of the ICRF power is damped resonantly on core ions (ω = 2 ω cD = 3 ω cT ) contributing to the ion heating. In NBI step-down experiments, high performance has been sustained by maintaining central ICRH heating; analysis shows the efficiency of central ICRH ion heating to be comparable with that of NBI. The highest D-D fusion neutron rates (R NT = 5.6 x 10 16 s -1 ) yet achieved in JET plasmas have been produced by combining a low magnetic shear core with a high confinement (H-mode) edge. In D-T, a fusion triple product n i T i τ E = (1.2 ± 0.2) x 10 21 m -3 keVs was achieved with 7.2 MW of fusion power obtained in the L-mode and up to 8.2 MW of fusion power in the H-mode phase. (author)

High performance with modified shear in JET D-D and D-T plasmas

International Nuclear Information System (INIS)

2001-01-01

The observation of Internal Transport Barriers (ITBs) in which ion thermal diffusivity is reduced to a neo- classical level and the electron thermal diffusivity is substantially reduced has been made in JET with the optimised shear scenario with the MkII divertor both in D-D and in D-T. Central ion temperatures of 40keV and plasma pressure gradient of 10 6 Pa/m were observed in D-T leading to a fusion triple product n i T i τ E =1x10 21 m -3 keVs and 8.2MW of fusion power. ITBs have also been produced in the new Gas Box divertor configuration with a similar behaviour. With the new divertor an L-mode edge has only been produced using edge radiation cooling. For the first time, ITBs have been triggered by radiating about 40% of the power with a krypton puff. A tentative scaling of the power needed to trigger an ITB with magnetic field is indicated. (author)

Effect of electronic coupling of Watson-Crick hopping in DNA poly(dA)-poly(dT)

Science.gov (United States)

Risqi, A. M.; Yudiarsah, E.

2017-07-01

Charge transport properties of poly(dA)-poly(dT) DNA has been studied by using thigh binding Hamiltonian approach. Molecule DNA that we use consist of 32 base pair of adenine (A) and thymine (T) and backbone is consist of phosphate and sugar. The molecule DNA is contacted electrode at both ends. Charge transport in molecule DNA depend on the environment, we studied the effect of electronic coupling of Watson-Crick hopping in poly(dA)-poly(dT) DNA to transmission probability and characteristic I-V. The electronic coupling constant influence charge transport between adenine-thymine base pairs at the same site. Transmission probability is studied by using transfer matrix and scattering matrix method, and the result of transmission probability is used to calculate the characteristic I-V by using formula Landauer Buttiker. The result shows that when the electronic coupling increase then transmission probability and characteristic I-V increase slightly.

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

Comparative study of genetic influence on the susceptibility of exotic ...

African Journals Online (AJOL)

This study investigated comparatively the genetic influence on the susceptibility of exotic cockerels, pullets and broilers to natural infection with infectious bursal disease (IBD) virus in a flock of 150 seven-week-old exotic breed of chickens comprising of 50 Black Harco cockerels, 50 Black Harco pullets and 50 White ...

The influence of early exposure to vitamin D for development of diseases later in life

DEFF Research Database (Denmark)

Jacobsen, Ramune; Abrahamsen, Bo; Bauerek, Marta Jadwiga

2013-01-01

Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied....... The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood....

3D T2-weighted imaging to shorten multiparametric prostate MRI protocols.

Science.gov (United States)

Polanec, Stephan H; Lazar, Mathias; Wengert, Georg J; Bickel, Hubert; Spick, Claudio; Susani, Martin; Shariat, Shahrokh; Clauser, Paola; Baltzer, Pascal A T

2018-04-01

To determine whether 3D acquisitions provide equivalent image quality, lesion delineation quality and PI-RADS v2 performance compared to 2D acquisitions in T2-weighted imaging of the prostate at 3 T. This IRB-approved, prospective study included 150 consecutive patients (mean age 63.7 years, 35-84 years; mean PSA 7.2 ng/ml, 0.4-31.1 ng/ml). Two uroradiologists (R1, R2) independently rated image quality and lesion delineation quality using a five-point ordinal scale and assigned a PI-RADS score for 2D and 3D T2-weighted image data sets. Data were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/area under the curve (AUC) analysis. Image quality was similarly good to excellent for 2D T2w (mean score R1, 4.3 ± 0.81; R2, 4.7 ± 0.83) and 3D T2w (mean score R1, 4.3 ± 0.82; R2, 4.7 ± 0.69), p = 0.269. Lesion delineation was rated good to excellent for 2D (mean score R1, 4.16 ± 0.81; R2, 4.19 ± 0.92) and 3D T2w (R1, 4.19 ± 0.94; R2, 4.27 ± 0.94) without significant differences (p = 0.785). ROC analysis showed an equivalent performance for 2D (AUC 0.580-0.623) and 3D (AUC 0.576-0.629) T2w (p > 0.05, respectively). Three-dimensional acquisitions demonstrated equivalent image and lesion delineation quality, and PI-RADS v2 performance, compared to 2D in T2-weighted imaging of the prostate. Three-dimensional T2-weighted imaging could be used to considerably shorten prostate MRI protocols in clinical practice. • 3D shows equivalent image quality and lesion delineation compared to 2D T2w. • 3D T2w and 2D T2w image acquisition demonstrated comparable diagnostic performance. • Using a single 3D T2w acquisition may shorten the protocol by 40%. • Combined with short DCE, multiparametric protocols of 10 min are feasible.

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

Science.gov (United States)

Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

2014-01-09

Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

Science.gov (United States)

Gross, Noah B; Duncker, Patrick C; Marshall, John F

2011-11-01

Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

Vitamin D controls T cell antigen receptor signaling and activation of human T cells

DEFF Research Database (Denmark)

von Essen, Marina Rode; Kongsbak-Wismann, Martin; Schjerling, Peter

2010-01-01

Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Here we show that naive human T cells had very low expression of PLC-gamma1 and that this correlated with low T cell antigen receptor (TCR) responsiveness in naive T cells. However, TCR triggering...... led to an upregulation of approximately 75-fold in PLC-gamma1 expression, which correlated with greater TCR responsiveness. Induction of PLC-gamma1 was dependent on vitamin D and expression of the vitamin D receptor (VDR). Naive T cells did not express VDR, but VDR expression was induced by TCR...... signaling via the alternative mitogen-activated protein kinase p38 pathway. Thus, initial TCR signaling via p38 leads to successive induction of VDR and PLC-gamma1, which are required for subsequent classical TCR signaling and T cell activation....

Magnetic ordering of quasi-1 D S=1/2 Heisenberg antiferromagnet Cu benzoate at sub-mK temperatures

International Nuclear Information System (INIS)

Karaki, Y.; Masutomi, R.; Kubota, M.; Ishimoto, H.; Asano, T.; Ajiro, Y.

2003-01-01

We have measured the AC susceptibility of quasi-1D S=1/2 Heisenberg antiferromagnet Cu benzoate at temperatures down to 0.2 mK. A sharp susceptibility peak is observed at 0.8 mK under an earth field. This fact indicates a 3D ordering of linear chains coupled by a weak magnetic interaction between chains

Insecticide susceptibility status of human biting mosquitoes in ...

African Journals Online (AJOL)

Matowo Pc

91.5% (n=483) and An. funestus group was 8.5% (n=45). ..... Chitnis, N., Churcher, T., Donnelly, M.J., Ghani, A.C., Godfray, H.C.J., Gould, F., Hastings, ... Efficacy, persistence and vector susceptibility to pirimiphos-methyl (Actellic® 300CS) insecticide ... Macoris, M.L., Andrighetti, M.T.M., Wanderley, D.M.V. & Ribolla, P.E.M. ...

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

Directory of Open Access Journals (Sweden)

Alexander Zhyvoloup

2017-07-01

Full Text Available HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.

Science.gov (United States)

Zhyvoloup, Alexander; Melamed, Anat; Anderson, Ian; Planas, Delphine; Lee, Chen-Hsuin; Kriston-Vizi, Janos; Ketteler, Robin; Merritt, Andy; Routy, Jean-Pierre; Ancuta, Petronela; Bangham, Charles R M; Fassati, Ariberto

2017-07-01

HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two main gene networks down-regulated by the drug were CD40L and CD38. Blocking CD40L by neutralizing antibodies selectively inhibited WT virus infection, phenocopying digoxin. Thus the selectivity of digoxin depends on a combination of integration targeting and repression of specific gene networks. The drug unmasked a functional connection between HIV-1 integration and T-cell activation. Our results suggest that HIV-1 evolved integration site selection to couple its early gene expression with the status of target CD4+ T-cells, which may affect latency and viral reactivation.

Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation, and Increases HIV-1 Integration in CD4+ T Cells.

Science.gov (United States)

Bolduc, Jean-François; Hany, Laurent; Barat, Corinne; Ouellet, Michel; Tremblay, Michel J

2017-08-15

In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4 + T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4 + T cells upon acetate treatment. This enhancing effect correlates with increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration into the genome of CD4 + T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence that acetate can also increase the susceptibility of primary human CD4 + T cells to productive HIV-1 infection. IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damage involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids, bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by epigenetic regulatory mechanisms, such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4 + T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression. Copyright © 2017 American Society for Microbiology.

Levels of 25(OHD3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM Receiving Vitamin D3 Supplementation

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Tjahyo Suryanto

2018-01-01

Full Text Available Type 1 Diabetes Mellitus (T1DM has become a health problem in many countries. T1DM is the consequence of autoimmune destruction process of β cells. There was relationship between vitamin D deficiency with T1DM. The destruction process was caused by an imbalance of pro-inflammatory and anti-inflammatory cytokines. One of the pro-inflammatory cytokines is IL-2. C-peptide examination to see the function of beta cells due to destruction of pancreatic beta cell. Administration of vitamin D3 supplementation still cause controversy and give varying results. This randomized clinical trial was conducted to determine the levels of 25(OHD3, IL-2, and C-peptide in people with T1DM who received vitamin D3 supplementation. The subjects were 26 children with T1DM, divided into K1 group (received vitamin D3 supplementation and K2 group (received placebo. The results showed higher levels of 25(OHD3 in the K1 group and statistically found a significant difference (p = 0.00. Higher levels of IL-2 and lower C-peptide were obtained in the K1 group and no statistically significant differences were found (p = 0.76 and p= 0.26. The insignificant relationship and the negative correlation were found between 25(OHD3 and IL-2 (p = 0.71; r = - 0.12, 25(OHD3 and C-peptide (p = 0.59; r = -0.16, also levels of IL-2 and C-peptide (p = 0.13; r = -0.44 in children with type 1 diabetes who received vitamin D3 supplementation. From this study can be concluded that administration vitamin D3 supplementation in patients with T1DM can increase levels 25(OHD3 significantly. This increase has not significantly lowered levels of IL-2 and increased levels of C-peptide. However, there was an absolute decrease in the rate of slower C-peptide in the supplemented group than in the placebo group.

High Performance Programming Using Explicit Shared Memory Model on Cray T3D1

Science.gov (United States)

Simon, Horst D.; Saini, Subhash; Grassi, Charles

1994-01-01

The Cray T3D system is the first-phase system in Cray Research, Inc.'s (CRI) three-phase massively parallel processing (MPP) program. This system features a heterogeneous architecture that closely couples DEC's Alpha microprocessors and CRI's parallel-vector technology, i.e., the Cray Y-MP and Cray C90. An overview of the Cray T3D hardware and available programming models is presented. Under Cray Research adaptive Fortran (CRAFT) model four programming methods (data parallel, work sharing, message-passing using PVM, and explicit shared memory model) are available to the users. However, at this time data parallel and work sharing programming models are not available to the user community. The differences between standard PVM and CRI's PVM are highlighted with performance measurements such as latencies and communication bandwidths. We have found that the performance of neither standard PVM nor CRI s PVM exploits the hardware capabilities of the T3D. The reasons for the bad performance of PVM as a native message-passing library are presented. This is illustrated by the performance of NAS Parallel Benchmarks (NPB) programmed in explicit shared memory model on Cray T3D. In general, the performance of standard PVM is about 4 to 5 times less than obtained by using explicit shared memory model. This degradation in performance is also seen on CM-5 where the performance of applications using native message-passing library CMMD on CM-5 is also about 4 to 5 times less than using data parallel methods. The issues involved (such as barriers, synchronization, invalidating data cache, aligning data cache etc.) while programming in explicit shared memory model are discussed. Comparative performance of NPB using explicit shared memory programming model on the Cray T3D and other highly parallel systems such as the TMC CM-5, Intel Paragon, Cray C90, IBM-SP1, etc. is presented.

Intrinsic functional brain mapping in reconstructed 4D magnetic susceptibility (χ) data space.

Science.gov (United States)

Chen, Zikuan; Calhoun, Vince

2015-02-15

By solving an inverse problem of T2*-weighted magnetic resonance imaging for a dynamic fMRI study, we reconstruct a 4D magnetic susceptibility source (χ) data space for intrinsic functional mapping. A 4D phase dataset is calculated from a 4D complex fMRI dataset. The background field and phase wrapping effect are removed by a Laplacian technique. A 3D χ source map is reconstructed from a 3D phase image by a computed inverse MRI (CIMRI) scheme. A 4D χ data space is reconstructed by repeating the 3D χ source reconstruction for each time point. A functional map is calculated by a temporal correlation between voxel signals in the 4D χ space and the timecourse of the task paradigm. With a finger-tapping experiment, we obtain two 3D functional mappings in the 4D magnitude data space and in the reconstructed 4D χ data space. We find that the χ-based functional mapping reveals co-occurrence of bidirectional responses in a 3D activation map that is different from the conventional magnitude-based mapping. The χ-based functional mapping can also be achieved by a 3D deconvolution of a phase activation map. Based on a subject experimental comparison, we show that the 4D χ tomography method could produce a similar χ activation map as obtained by the 3D deconvolution method. By removing the dipole effect and other fMRI technological contaminations, 4D χ tomography provides a 4D χ data space that allows a more direct and truthful functional mapping of a brain activity. Published by Elsevier B.V.

A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility

Directory of Open Access Journals (Sweden)

Xiuju Chen

2016-01-01

Full Text Available Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE and China National Knowledge Infrastructure (CNKI. All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg’s funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05. People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.

Comparison of multiple quantitative MRI parameters for characterization of the goat cartilage in an ongoing osteoarthritis: dGEMRIC, T1ρ and sodium

International Nuclear Information System (INIS)

Schrauth, Joachim H.X.; Lykowsky, Gunthard; Hemberger, Kathrin; Kreutner, Jakob; Jakob, Peter M.; Weber, Daniel; Haddad, Daniel; Rackwitz, Lars; Noeth, Ulrich

2016-01-01

Osteoarthritis (OA) is a degenerative joint disease leading to cartilage deterioration by loss of matrix, fibrillation, formation of fissures, and ultimately complete loss of the cartilage surface. Here, three magnetic resonance imaging (MRI) techniques, dGEMRIC (delayed Gadolinium enhanced MRI of cartilage; dG 1 = T 1,post ; dG 2 = 1/T 1,post -1/T 1,pre ), T 1ρ , and sodium MRI, are compared in a preclinical in vivo study to evaluate the differences in their potential for cartilage characterization and to establish an examination protocol for a following clinical study. OA was induced in 12 caprine knees (6 control, 6 therapy). Adipose derived stem cells were injected afterwards as a treatment. The animals were examined healthy, 3 and 16 weeks postoperatively with all three MRI methods. Using statistical analysis, the OA development and the degree of correlation between the different MRI methods were determined. A strong correlation was observed between the dGEMRIC indices dG 1 and dG 2 (r=-0.87) which differ only in considering or not considering the T 1 baseline. Moderate correlations were found between T 1ρ and dG 1 (r=0.55), T 1ρ and dG 2 (r=0.47) and at last, sodium and dG 1 (r=0.45). The correlations found in this study match to the biomarkers which the methods are sensitive to. Even though the goat cartilage is significantly thinner than the human cartilage and even more in a degenerated cartilage, all three methods were able to characterize the cartilage over the whole period of time during an ongoing OA.Due to measurement and post processing optimizations, as well as the correlations detected in this work, the overall measurement time in future goat studies can be minimized. Moreover, an examination protocol for characterizing the cartilage in a clinical study was established.

Detecting ICRS grade 1 cartilage lesions in anterior cruciate ligament injury using T1ρ and T2 mapping

Energy Technology Data Exchange (ETDEWEB)

Nishioka, Hiroaki, E-mail: kinuhnishiok@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Hirose, Jun, E-mail: hirojun-mk@umin.ac.jp [Department of Orthopaedic Surgery, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Nakamura, Eiichi, E-mail: h@kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Okamoto, Nobukazu, E-mail: nobuoka9999@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Karasugi, Tatsuki, E-mail: tatsukik@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Taniwaki, Takuya, E-mail: takuyataniwaki@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Okada, Tatsuya, E-mail: tatsuya-okada@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Yamashita, Yasuyuki, E-mail: yama@kumamoto-u.ac.jp [Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Mizuta, Hiroshi, E-mail: mizuta@kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan)

2013-09-15

Objective: The purpose of this study was to clarify the detectability of the International Cartilage Repair Society (ICRS) grade 1 cartilage lesions in anterior cruciate ligament (ACL)–injured knees using T1ρ and T2 mapping. Materials and Methods: We performed preoperative T1ρ and T2 mapping and 3D gradient–echo with water–selective excitation (WATS) sequences on 37 subjects with ACL injuries. We determined the detectability on 3D WATS based on arthroscopic findings. The T1ρ and T2 values (ms) were measured in the regions of interest that were placed on the weight–bearing cartilage of the femoral condyle. The receiver operating characteristic (ROC) curve based on these values was constructed using the arthroscopic findings as a reference standard. The evaluation of cartilage was carried out only in the weight–bearing cartilage. The cut–off values for determining the presence of a cartilage injury were determined using each ROC curve, and the detectability was calculated for the T1ρ and T2 mapping. Results: The cut–off values for the T1ρ and T2 were 41.6 and 41.2, respectively. The sensitivity and specificity of T1ρ were 91.2% and 89.5%, respectively, while those of T2 were 76.5% and 81.6%, respectively. For the 3D WATS images, the same values were 58.8% and 78.9%, respectively. Conclusions: Our study demonstrated that the T1ρ and T2 values were significantly higher for ICRS grade 1 cartilage lesions than for normal cartilage and that the two mappings were able to non–invasively detect ICRS grade 1 cartilage lesions in the ACL–injured knee with a higher detectability than were 3D WATS images.

Combined MRI and MRS in prostate cancer. Improvement of spectral quality by susceptibility matching

Energy Technology Data Exchange (ETDEWEB)

Scheidler, J.; Heuck, A. [Radiologisches Zentrum Muenchen-Pasing (Germany). Radiologie; Vogel, M.; Gross, P. [GE Global Research (Germany)

2009-06-15

Purpose: local magnetic field inhomogeneity caused by susceptibility artifacts due to air in the endorectal coil substantially degrades the quality of 3D MR spectroscopic imaging (3D-MRSI). Perflubron (PFB) has magnetic susceptibility similar to that of human tissue. We prospectively assessed the effect of susceptibility matching using PFB on in vivo prostate {sup 1}H-3D-MRSI. Materials and methods: ninety-one consecutive patients referred for 3D-MRSI were examined using air and PFB as the filling agent for endorectal coils at 1.5T with an identically placed PRESS box and sat bands. Solely auto-shim without additional manual shimming was used. The full width at half maximum (FWHM) of the water peak was statistically compared with a paired t-test. The spectral quality was visually evaluated for the definition of metabolite peaks and for the citrate peak split (duplet). The MR image quality was rated on a five-point scale. Results: FWHM was significantly less (p < 0.001) using PFB (mean 9.0 {+-} 3.3, range 3 - 20) than air (mean 14.9 {+-} 4.2, range 6 - 26) in 85/91 patients (93%). The spectral quality markedly improved using PFB and frequently the duplet of the citrate peak was able to be identified. Image quality ratings were similar (mean rating PFB 4.2, air 4.3 points). Omitting manual shimming led to a time savings of 4 min. per study. (orig.)

Combined MRI and MRS in prostate cancer. Improvement of spectral quality by susceptibility matching

International Nuclear Information System (INIS)

Scheidler, J.; Heuck, A.

2009-01-01

Purpose: local magnetic field inhomogeneity caused by susceptibility artifacts due to air in the endorectal coil substantially degrades the quality of 3D MR spectroscopic imaging (3D-MRSI). Perflubron (PFB) has magnetic susceptibility similar to that of human tissue. We prospectively assessed the effect of susceptibility matching using PFB on in vivo prostate 1 H-3D-MRSI. Materials and methods: ninety-one consecutive patients referred for 3D-MRSI were examined using air and PFB as the filling agent for endorectal coils at 1.5T with an identically placed PRESS box and sat bands. Solely auto-shim without additional manual shimming was used. The full width at half maximum (FWHM) of the water peak was statistically compared with a paired t-test. The spectral quality was visually evaluated for the definition of metabolite peaks and for the citrate peak split (duplet). The MR image quality was rated on a five-point scale. Results: FWHM was significantly less (p < 0.001) using PFB (mean 9.0 ± 3.3, range 3 - 20) than air (mean 14.9 ± 4.2, range 6 - 26) in 85/91 patients (93%). The spectral quality markedly improved using PFB and frequently the duplet of the citrate peak was able to be identified. Image quality ratings were similar (mean rating PFB 4.2, air 4.3 points). Omitting manual shimming led to a time savings of 4 min. per study. (orig.)

The influence of a single nucleotide polymorphism within CNDP1 on susceptibility to diabetic nephropathy in Japanese women with type 2 diabetes.

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Mahiro Kurashige

Full Text Available BACKGROUND: Several linkage analyses have mapped a susceptibility locus for diabetic nephropathy to chromosome 18q22-23, and polymorphisms within the carnosine dipeptidase 1 gene (CNDP1, located on 18q22.3, have been shown to be associated with diabetic nephropathy in European subjects with type 2 diabetes. However, the association of this locus with diabetic nephropathy has not been evaluated in the Japanese population. In this study, we examined the association of polymorphisms within the CNDP1/CNDP 2 locus with diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped a leucine repeat polymorphism (D18S880 that is within CNDP1 along with 29 single nucleotide polymorphisms (SNPs in the CNDP1/CNDP2 locus for 2,740 Japanese subjects with type 2 diabetes (1,205 nephropathy cases with overt nephropathy or with end-stage renal disease [ESRD], and 1,535 controls with normoalbuminuria. The association of each polymorphism with diabetic nephropathy was analysed by performing logistic regression analysis. We did not observe any association between D18S880 and diabetic nephropathy in Japanese subjects with type 2 diabetes. None of the 29 SNPs within the CNDP1/CNDP2 locus were associated with diabetic nephropathy, but a subsequent sex-stratified analysis revealed that 1 SNP in CNDP1 was nominally associated with diabetic nephropathy in women (rs12604675-A; p = 0.005, odds ratio [OR] = 1.76, 95% confidence interval [CI], 1.19-2.61. Rs12604675 was associated with overt proteinuria (p = 0.002, OR = 2.18, 95% CI, 1.32-3.60, but not with ESRD in Japanese women with type 2 diabetes. CONCLUSIONS/SIGNIFICANCE: Rs12604675-A in CNDP1 may confer susceptibility to overt proteinuria in Japanese women with type 2 diabetes.

Weak cooperativity in selected iron(II) 1D coordination polymers

International Nuclear Information System (INIS)

Dîrtu, Marinela M.; Gillard, Damien; Naik, Anil D.; Rotaru, Aurelian; Garcia, Yann

2012-01-01

The spin crossover behaviour of a new class of Fe II coordination polymers [Fe(phtptrz) 3 ]I 2 (1), [Fe(phtptrz) 3 ](ReO 4 ) 2 •CH 3 OH (2) and [Fe(phtptrz) 3 ]TaF 7 •6H 2 O (3) based on a novel ligand 4-(3 ′ -N-phtalimido-propyl)-1,2,4-triazole (phtptrz), were investigated by temperature dependent 57 Fe Mössbauer spectroscopy and magnetic susceptibility measurements. The adverse effect of bulky substituent on 1,2,4-triazole, favorable supramolecular interactions and influence of increasing anion size on spin crossover profile is discussed. 1 and 2 show thermally induced spin conversions of gradual and incomplete nature with associated thermochromism, and transition temperatures T 1/2 ∼ 163 K and 137 K, respectively. A spin state crossover is also identified for 3.

Influence of delta ferrite on corrosion susceptibility of AISI 304 austenitic stainless steel

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Lawrence O. Osoba

2016-12-01

Full Text Available In the current study, the influence of delta (δ ferrite on the corrosion susceptibility of AISI 304 austenitic stainless steel was evaluated in 1Molar concentration of sulphuric acid (H2SO4 and 1Molar concentration of sodium chloride (NaCl. The study was performed at ambient temperature using electrochemical technique—Tafel plots to evaluate the corrosive tendencies of the austenitic stainless steel sample. The as-received (stainless steel specimen and 60% cold-worked (stainless steel specimens were isothermally annealed at 1,100°C for 2 h and 1 h, respectively, and quenched in water. The results obtained show that the heat-treated specimen and the 60% cold-worked plus heat-treated specimen exhibited higher corrosion susceptibility than the as-received specimen, which invariably contained the highest fraction of δ ferrite particles. The finding shows that the presence of δ ferrite, in which chromium (Cr, the main corrosion inhibitor segregates, does not degrade and or reduces the resistance to aqueous corrosion of the austenitic stainless steel material.

P3-1: Ophthalmologic Factors Influencing Asthenopia with Watching 3D Displays

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Sungwook Wee

2012-10-01

Full Text Available Purpose: To identify ophthalmologic factors influencing asthenopia while watching 3D displays. Methods: 30 adult subjects without ophthalmologic abnormality watched the same 3D displays for 30 minutes. Each subject's far and near visual acuity, near points of accommodation and convergence, amplitude of fusional convergence and divergence, stereopsis, angle of phoric deviation, tear break-up time, and temperature of ocular surface before and after watching 3D displays were measured. And surveys for subjective symptoms right after watching 3D displays were conducted. The above-mentioned experiments were performed equally with 2D displays for detection of innate influence of 3D displays. Results: The near points of accommodation and convergence were significantly changed after watching 3D displays (p < .05 compared to 2D displays. And all 10 subjective symptoms were significantly increased after watching 3D displays (p < .05. Conclusion: The accommodation and binocular vergence are predominant ophthalmologic factors that might influence asthenopia significantly while watching 3D displays. Subjective visual discomfort significantly increases with watching 3D displays, and more specific evaluation should be added for detecting the practically related factors with asthenopia.

Identification and in vitro analysis of the GatD/MurT enzyme-complex catalyzing lipid II amidation in Staphylococcus aureus.

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Daniela Münch

2012-01-01

Full Text Available The peptidoglycan of Staphylococcus aureus is characterized by a high degree of crosslinking and almost completely lacks free carboxyl groups, due to amidation of the D-glutamic acid in the stem peptide. Amidation of peptidoglycan has been proposed to play a decisive role in polymerization of cell wall building blocks, correlating with the crosslinking of neighboring peptidoglycan stem peptides. Mutants with a reduced degree of amidation are less viable and show increased susceptibility to methicillin. We identified the enzymes catalyzing the formation of D-glutamine in position 2 of the stem peptide. We provide biochemical evidence that the reaction is catalyzed by a glutamine amidotransferase-like protein and a Mur ligase homologue, encoded by SA1707 and SA1708, respectively. Both proteins, for which we propose the designation GatD and MurT, are required for amidation and appear to form a physically stable bi-enzyme complex. To investigate the reaction in vitro we purified recombinant GatD and MurT His-tag fusion proteins and their potential substrates, i.e. UDP-MurNAc-pentapeptide, as well as the membrane-bound cell wall precursors lipid I, lipid II and lipid II-Gly₅. In vitro amidation occurred with all bactoprenol-bound intermediates, suggesting that in vivo lipid II and/or lipid II-Gly₅ may be substrates for GatD/MurT. Inactivation of the GatD active site abolished lipid II amidation. Both, murT and gatD are organized in an operon and are essential genes of S. aureus. BLAST analysis revealed the presence of homologous transcriptional units in a number of gram-positive pathogens, e.g. Mycobacterium tuberculosis, Streptococcus pneumonia and Clostridium perfringens, all known to have a D-iso-glutamine containing PG. A less negatively charged PG reduces susceptibility towards defensins and may play a general role in innate immune signaling.

E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient.

Science.gov (United States)

L'Huillier, Arnaud G; Abed, Yacine; Petty, Tom J; Cordey, Samuel; Thomas, Yves; Bouhy, Xavier; Schibler, Manuel; Simon, Audrey; Chalandon, Yves; van Delden, Christian; Zdobnov, Evgeny; Boquete-Suter, Patricia; Boivin, Guy; Kaiser, Laurent

2015-12-01

An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategies. © The Author 2015. 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.

Harmonic and static susceptibilities of YBa2Cu3O7

International Nuclear Information System (INIS)

Ishida, T.; Goldfarb, R.B.; Okayasu, S.; Kazumata, Y.; Franz, J.; Arndt, T.; Schauer, W.

1993-01-01

Intergranular properties of the sintered superconductor YBa 2 Cu 3 O 7 have been studied in terms of complex harmonic magnetic susceptibility χ n χ n ' - iχ n '' (n integer) as well as DC susceptibility χ dc . As functions of temperature T, χ 1 ' and χ 1 '' depend on both the AC magnetic-field amplitude H ac and the magnitude of a superimposed DC field H dc . Only odd-harmonic susceptibilities are observed below the critical temperature, T c , for zero H dc while both odd and even harmonics are observed for nonzero H dc . With T constant, odd-harmonic susceptibilities are even functions of H dc , whereas even-harmonic susceptibilities are odd functions of H dc . Experimental intergranular characteristics of χ n ' and χ n '' are in good agreement with theoretical predictions from a simplified Kim model of magnetization. In contrast, even-harmonic susceptibilities measured for a GdBa 2 Cu 3 O 7 thin film and an YBa 2 Cu 3 O 7 single crystal are not prominent due to missing weak links, whereas odd-harmonic susceptibilities are remarkable. A survey of several models for the harmonic response of superconductors is presented. The DC susceptibility curve for the zero-field-cooled YBa 2 Cu 3 O 7 sample, χ ZFC (T), has a two-step structure arising from intra- and inter-granular components, similar to χ 1 '. DC susceptibility measured upon warming, χ FCW (T), shows a negative peak near T c for the sample cooled rapidly in small DC fields. DC susceptibility measured upon cooling, χ FCC (T), does not show a peak. A negative peak is not seen in measurements on a powdered sample. The negative peak can be explained by intergranular flux depinning upon warming. (orig.)

Susceptibility of Diaphorina citri (Hemiptera: Liviidae) and Its Parasitoid Tamarixia radiata (Hymenoptera: Eulophidae) to Entomopathogenic Fungi under Laboratory Conditions.

Science.gov (United States)

Ibarra-Cortés, K H; Guzmán-Franco, A W; González-Hernández, H; Ortega-Arenas, L D; Villanueva-Jiménez, J A; Robles-Bermúdez, A

2018-02-01

Diaphorina citri (Kuwayama) is a global pest of citrus that transmits the bacteria associated with the disease, Huanglongbing. Entomopathogenic fungi and the parasitoid Tamarixia radiata (Waterston) are important biological control agents of this pest and likely to interact in D. citri populations. As a basis for interaction studies, we determined the susceptibility of nymphs and adults of D. citri and adults of the parasitoid T. radiata to six fungal isolates from the species Beauveria bassiana s.l. (Bals.-Criv.) Vuill. (isolates B1 and B3), Metarhizium anisopliae s.s. (Metsch.) (Ma129 and Ma65) and Isaria fumosorosea Wize (I2 and Pae). We conducted experiments evaluating infection levels in all three insect groups following inoculation with a series of conidial concentrations (1 × 10 4 -1 × 10 8 conidia mL -1 ). Results showed that D. citri nymphs and T. radiata were more susceptible to fungal isolates than D. citri adults. Overall, B. bassiana and M. anisopliae isolates caused the greatest infection compared with I. fumosorosea isolates in all three groups of insects. Isolates B1 (B. bassiana) and Ma129 (M. anisopliae) infected a greater proportion of adults and nymphs of D. citri, respectively. Both isolates of B. bassiana caused greater infection in T. radiata compared with isolates of the other fungal species. We propose that isolates B1 and Ma129 are the strongest candidates for control of D. citri. Our results represent the first report of entomopathogenic fungi infecting T. radiata, and the basis for future studies to design a biological control programme that uses both agents more efficiently against D. citri populations.

Role of the d -d interaction in the antiferromagnetic phase of λ -(BEDT-STF ) 2FeCl4

Science.gov (United States)

Minamidate, Takaaki; Shindo, Hironori; Ihara, Yoshihiko; Kawamoto, Atsushi; Matsunaga, Noriaki; Nomura, Kazushige

2018-03-01

Magnetic susceptibility and proton nuclear magnetic resonance (1H-NMR ) measurements were performed for the quasi-two-dimensional π -d interacting system λ -(BEDT-STF ) 2FeCl4 at ambient pressure. Magnetic susceptibility arising from the 3 d spins of the FeCl4 anion show an anisotropy at low temperature and its temperature dependence for the external field parallel to the c axis is described as a broad peak structure at 8 K. A sharp peak in the temperature dependence of T1-1 associated with the antiferromagnetic (AF) transition is observed at TAF=16 K, together with the drastic splitting of the NMR spectrum below TAF. The relation between the static susceptibility and the splitting of the NMR shift suggests the existence of the relatively strong d -d AF interaction. These results can be explained by the model considering the AF-coupled d -spin system in the AF long-range-ordered π -spin system. We find that the AF phases in λ -type salts can be universally explained by this model.

Abrupt symmetry decrease in the ThT2Al20 alloys (T = 3d transition metal)

International Nuclear Information System (INIS)

Uziel, A.; Bram, A.I.; Venkert, A.; Kiv, A.E.; Fuks, D.; Meshi, L.

2015-01-01

Th-T-Al system, where T-3d transition metals, was studied at ThT 2 Al 20 stoichiometry to establish the influence of T on the structural stability of ternary aluminide formed. Different alloys were prepared, varying T in the row from Ti to Fe. Using electron microscopy and X-ray diffraction methods it was found that ThT 2 Al 20 phase adopts CeCr 2 Al 20 structure type when T = Ti, V, and Cr. Starting from Mn, the symmetry of the stable Al-rich phase, which forms in the alloys with the same composition, decreases from cubic to orthorhombic. The results of Density Functional Theory (DFT) calculations coincide with experiments. Concepts of the Theory of Coordination Compounds and Jahn–Teller effect were used to explain the observed abrupt change of the symmetry. These considerations were supported by DFT calculations. - Highlights: • Type of transition metal influences symmetry change in the ThT 2 Al 20 alloys. • It was found that cubic ThT 2 Al 20 phase is stable for T = Ti, V and Cr. • When T = Mn, Fe–Al + orthorhombic ThT 2 Al 10 are formed, lowering the symmetry. • Experimental results and DFT calculations were in full agreement. • TCC and of Jahn–Teller effect were used for explanation of the results

D-T axicell magnet system for MFTF-α+T

International Nuclear Information System (INIS)

Srivastava, V.C.

1983-01-01

The configuration and design of the deuterium-tritium (D-T) axicell superconducting magnets for the Mirror Fusion Test Facility (MFTF-α+T) are described. The MFTF-α+T is an upgrade of the MFTF-B, with new end-plug magnets and a neutron-producing central D-T axicell section. The 4-m long axicell - its length defined by the 12-T peaks in the mirror field - is beam fueled and heated by two beam lines, each with four neutral beam injection ports. Two large superconducting coils (means diameter approx. 3.8 m) located at Z = +-2.40 m, in conjunction with a small copper coil located outside the test volume region, produce the 4.5-T mirror midplane field. This background field is augmented by two copper coils to create the 12-T peak mirror fields at Z = +-2 m. The central region of the axicell accommodates a 1-m-long, replaceable blanket test module. The length (4 m) of the axicell was chosen to provide relatively uniform neutron wall loading over the test module. In many respects, this axicell is less than full scale, but it could be viewed as a short section of a reactor, complete with the support systems and technologies associated with a mirror reactor. The peak field at the superconducting coils is 10.8 T. The coils employ hybrid superconducting winding - Nb 3 Sn conductor in the 8- to 12-T region and NbTi in the 0- to 8-T region. The winding is cryostable and is cooled by a 4.2 K liquid helium bath. The conductor design, the winding design, and the performance analyses for these superconducting coils are described

Facteurs associés au diagnostic tardif d'un trouble de l'humeur et/ou d'anxiété

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Ricky Cheung

2017-01-01

Full Text Available Introduction : Cette étude examine les relations entre le délai écoulé avant l'établissement d'un diagnostic et les caractéristiques sociodémographiques et cliniques, ainsi que les relations entre ce délai de diagnostic et l'état de santé physique et mental des adultes canadiens ayant déclaré avoir reçu un diagnostic de trouble de l'humeur et/ou d'anxiété. Méthodologie : L'Enquête sur les personnes ayant une maladie chronique au Canada - Composante sur les troubles de l'humeur et d'anxiété de 2014 a été utilisée pour cette étude. L'échantillon de l'étude (n = 3 212 a été divisé en trois sous-groupes en fonction du délai de diagnostic : long (plus de 5 ans, modéré (1 à 5 ans et court (moins d'un an. Nous avons réalisé des analyses de régression logistique multivariées descriptives et multinomiales. Nous avons pondéré toutes les estimations afin que les données soient représentatives de la population canadienne adulte vivant en logement privé dans l'une des 10 provinces et ayant déclaré avoir reçu un diagnostic de troubles de l'humeur et/ou d'anxiété. Résultats : La plupart (61,6 % des adultes canadiens ayant déclaré avoir reçu un diagnostic de trouble de l'humeur et/ou d'anxiété ont dit avoir reçu leur diagnostic plus d'un an après l'apparition des symptômes (délai modéré : 30,0 %; délai long : 31,6 %. Après ajustement des caractéristiques individuelles, nous avons constaté qu'un délai modéré était significativement associé à la présence d'un faible nombre de comorbidités physiques ou d'aucune, qu'un délai long était significativement associé à un âge plus avancé, et qu'un délai long ou modéré étaient significativement associés à l'apparition de symptômes à un jeune âge. Finalement, un délai long était significativement associé à une santé mentale perçue comme « mauvaise » ou « passable » et à un nombre plus élevé de limitations d

Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

NARCIS (Netherlands)

Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

2012-01-01

OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

Differential Susceptibility: The Genetic Moderation of Peer Pressure on Alcohol Use

OpenAIRE

Griffin, Amanda M.; Cleveland, H. Harrington; Schlomer, Gabriel L.; Vandenbergh, David J.; Feinberg, Mark E.

2015-01-01

Although peer pressure can influence adolescents’ alcohol use, individual susceptibility to these pressures varies across individuals. The dopamine receptor D4 gene (DRD4) is a potential candidate gene that may influence adolescents’ susceptibility to their peer environment due to the role dopamine plays in reward sensation during social interaction. We hypothesized that DRD4 genotype status would moderate the impact of 7th-grade antisocial peer pressure on 12th-grade lifetime alcohol use (n ...

Titration of poly(dA-dT) . poly(dA-dT) in solution at variable NaCl concentration.

Science.gov (United States)

Airoldi, Marta; Boicelli, C Andrea; Cadoni, Fabio; Gennaro, Giuseppe; Giomini, Marcello; Giuliani, Anna M; Giustini, Mauro

2004-10-05

CD and uv absorption data showed that high molecular weight poly(dA-dT) . poly(dA-dT), at 298 K, undergoes an acid-induced transition from B-double helix to random coil in NaCl solutions of different concentrations, ranging from 0.005 to 0.600M. Similarly, titration of the polynucleotide with a strong base causes duplex-to-single strands transition. The base- and acid-induced transitions were both reversible by back-titration (with an acid or, respectively, with a base): the apparent pKa were the same in both directions. However, the number of protons per titratable site (adenine N1) required to reach half-denaturation was in great excess over the stoichiometric value; to a much larger extent, the same effect was observed also for the deprotonation of the N3H sites of thymine. Moreover, in the basic denaturation experiments, at low salt concentrations ([NaCl]acid than calculated was needed to back-titrate the base excess to half-denaturation. Both effects could be qualitatively justified on the basis of the counterion condensation theory of polyelectrolytes and considering the energy barrier created by the negatively charged phosphodiester groups to the penetration of the OH- ions inside the double helix and the screening effect of the Na+ ions on such charges, in the deprotonation experiments.

Fission multipliers for D-D/D-T neutron generators

International Nuclear Information System (INIS)

Lou, T.P.; Vujic, J.L.; Koivunoro, H.; Reijonen, J.; Leung, K.-N.

2003-01-01

A compact D-D/D-T fusion based neutron generator is being designed at the Lawrence Berkeley National Laboratory to have a potential yield of 10 12 D-D n/s and 10 14 D-T n/s. Because of its high neutron yield and compact size (∼20 cm in diameter by 4 cm long), this neutron generator design will be suitable for many applications. However, some applications required higher flux available from nuclear reactors and spallation neutron sources operated with GeV proton beams. In this study, a subcritical fission multiplier with k eff of 0.98 is coupled with the compact neutron generators in order to increase the neutron flux output. We have chosen two applications to show the gain in flux due to the use of fission multipliers--in-core irradiation and out-of-core irradiation. For the in-core irradiation, we have shown that a gain of ∼25 can be achieved in a positron production system using D-T generator. For the out-of-core irradiation, a gain of ∼17 times is obtained in Boron Neutron Capture Therapy (BNCT) using a D-D neutron generator. The total number of fission neutrons generated by a source neutron in a fission multiplier with k eff is ∼50. For the out-of-core irradiation, the theoretical maximum net multiplication is ∼30 due to the absorption of neutrons in the fuel. A discussion of the achievable multiplication and the theoretical multiplication will be presented in this paper

7 Tesla quantitative hip MRI: T1, T2 and T2* mapping of hip cartilage in healthy volunteers

Energy Technology Data Exchange (ETDEWEB)

Lazik, Andrea; Theysohn, Jens M.; Geis, Christina [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Johst, Soeren; Kraff, Oliver [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Ladd, Mark E. [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Medical Physics in Radiology, Heidelberg (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany)

2016-05-15

To evaluate the technical feasibility and applicability of quantitative MR techniques (delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 mapping, T2* mapping) at 7 T MRI for assessing hip cartilage. Hips of 11 healthy volunteers were examined at 7 T MRI with an 8-channel radiofrequency transmit/receive body coil using multi-echo sequences for T2 and T2* mapping and a dual flip angle gradient-echo sequence before (T1{sub 0}) and after intravenous contrast agent administration (T1{sub Gd}; 0.2 mmol/kg Gd-DTPA{sup 2-} followed by 0.5 h of walking and 0.5 h of rest) for dGEMRIC. Relaxation times of cartilage were measured manually in 10 regions of interest. Pearson's correlations between R1{sub delta} = 1/T1{sub Gd} - 1/T1{sub 0} and T1{sub Gd} and between T2 and T2* were calculated. Image quality and the delineation of acetabular and femoral cartilage in the relaxation time maps were evaluated using discrete rating scales. High correlations were found between R1{sub delta} and T1{sub Gd} and between T2 and T2* relaxation times (all p < 0.01). All techniques delivered diagnostic image quality, with best delineation of femoral and acetabular cartilage in the T2* maps (mean 3.2 out of a maximum of 4 points). T1, T2 and T2* mapping of hip cartilage with diagnostic image quality is feasible at 7 T. To perform dGEMRIC at 7 T, pre-contrast T1 mapping can be omitted. (orig.)

CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.

Science.gov (United States)

Lin, Zhijie; Wang, Changrong; Xia, Haizui; Liu, Weiguang; Xiao, Weiming; Qian, Li; Jia, Xiaoqin; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

2014-03-01

The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4(+) NKG2D(+) T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset. © 2013 John Wiley & Sons Ltd.

Comparison of preliminary D-T and ''catalyzed'' D-D system studies

International Nuclear Information System (INIS)

Usher, J.L.; Powell, J.R.; Fillo, J.A.; Lazareth, O.W.

1976-01-01

The purpose of the research currently underway is to provide technological and eventual economic comparison of a reference D-T reactor to a ''catalyzed'' D-D reactor. Two separate reactor designs are delineated and examined for this purpose. These systems include plasma parameters, blanket and shield configurations, magnetic coil configurations, and power conversion systems, including a divertor-direct convertor system for the D-D design. The initial conclusions reached are as follows: (a) no extraordinary requirements in the D-D reactor in the areas of blanket or magnet technology, (b) advantageous use of minimum activity blankets and shields, (c) increased overall efficiency via introduction of divertor-direct convertor subsystem in D-D design and (d) 65 percent increase in the toroidal radius of the D-D design compared to the D-T reference value

Differential susceptibility of RAE-1 isoforms to mouse cytomegalovirus.

Science.gov (United States)

Arapovic, Jurica; Lenac, Tihana; Antulov, Ronald; Polic, Bojan; Ruzsics, Zsolt; Carayannopoulos, Leonidas N; Koszinowski, Ulrich H; Krmpotic, Astrid; Jonjic, Stipan

2009-08-01

The NKG2D receptor is one of the most potent activating natural killer cell receptors involved in antiviral responses. The mouse NKG2D ligands MULT-1, RAE-1, and H60 are regulated by murine cytomegalovirus (MCMV) proteins m145, m152, and m155, respectively. In addition, the m138 protein interferes with the expression of both MULT-1 and H60. We show here that one of five RAE-1 isoforms, RAE-1delta, is resistant to downregulation by MCMV and that this escape has functional importance in vivo. Although m152 retained newly synthesized RAE-1delta and RAE-1gamma in the endoplasmic reticulum, no viral regulator was able to affect the mature RAE-1delta form which remains expressed on the surfaces of infected cells. This differential susceptibility to downregulation by MCMV is not a consequence of faster maturation of RAE-1delta compared to RAE-1gamma but rather an intrinsic property of the mature surface-resident protein. This difference can be attributed to the absence of a PLWY motif from RAE-1delta. Altogether, these findings provide evidence for a novel mechanism of host escape from viral immunoevasion of NKG2D-dependent control.

Inherited MST1 deficiency underlies susceptibility to EV-HPV infections.

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Amandine Crequer

Full Text Available Epidermodysplasia verruciformis (EV is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs in otherwise healthy individuals. Autosomal recessive (AR EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals.

Initial experience with 3T 3D-TOF MRA in the diagnosis of intracranial aneurysms

International Nuclear Information System (INIS)

Senba, Yoshiki; Takahashi, Shizue; Matsubara, Ichiro; Sadamoto, Kazuhiko; Miki, Hitoshi; Mochizuki, Teruhito

2006-01-01

We assessed the value of 3T 3D-time of flight (TOF) MR angiography (MRA) in the diagnosis of intracranial aneurysms compared with 1.5T 3D-TOF MRA. Twenty-one patients with 22 aneurysms underwent MRA at 1.5T and 3T. Images were interpreted by two radiologists. Each of nine aneurysms that had been considered ''definite'' at 1.5T 3D-TOF MRA were considered ''definite'' at 3T 3D-TOF MRA. Seven aneurysms that had been considered ''suspicious'' at 1.5T MRA were considered ''definite'' at 3T. And four aneurysms that had been considered ''suspicious'' at 1.5T were considered ''negative'' at 3T. We concluded that 3T 3D-TOF MRA is superior to 1.5T 3D-TOF MRA in the diagnosis of intracranial aneurysms. (author)

A novel solar multifunctional PV/T/D system for green building roofs

International Nuclear Information System (INIS)

Feng, Chaoqing; Zheng, Hongfei; Wang, Rui; Yu, Xu; Su, Yuehong

2015-01-01

Highlights: • A novel transparent roof combines the solar PV/T/D system with green building design. • Novel photovoltaic-thermal roofing design can achieve excellent light control at noon. • The roof has no obvious influence on indoor light intensity in morning and afternoon. • Higher efficiency of solar energy utilization could be achieved with new roofing. - Abstract: A novel transparent roof which is made of solid CPC (Compound Parabolic Concentrator) PV/T/D (Photovoltaic/Thermal/Day lighting) system is presented. It combines the solar PV/T/D system with green building design. The PV/T/D system can achieve excellent light control at noon and adjust the thermal environment in the building, such that high efficiency utilization of solar energy could be achieved in modern architecture. This kind of roof can increase the visual comfort for building occupants; it can also avoid the building interior from overheating and dazzling at noon which is caused by direct sunlight through transparent roof. Optical simulation software is used to track the light path in different incidence angles. CFD (Computational Fluid Dynamics) simulation and steady state experiment have been taken to investigate the thermal characteristic of PV/T/D device. Finally, the PV/T/D experimental system was built; and the PV efficiency, light transmittance and air heating power of the system are tested under real sky conditions

Differential susceptibility to parenting and quality child care.

Science.gov (United States)

Pluess, Michael; Belsky, Jay

2010-03-01

Research on differential susceptibility to rearing suggests that infants with difficult temperaments are disproportionately affected by parenting and child care quality, but a major U.S. child care study raises questions as to whether quality of care influences social adjustment. One thousand three hundred sixty-four American children from reasonably diverse backgrounds were followed from 1 month to 11 years with repeated observational assessments of parenting and child care quality, as well as teacher report and standardized assessments of children's cognitive-academic and social functioning, to determine whether those with histories of difficult temperament proved more susceptible to early rearing effects at ages 10 and 11. Evidence for such differential susceptibility emerges in the case of both parenting and child care quality and with respect to both cognitive-academic and social functioning. Differential susceptibility to parenting and child care quality extends to late middle childhood. J. Belsky, D. L. Vandell, et al.'s (2007) failure to consider such temperament-moderated rearing effects in their evaluation of long-term child care effects misestimates effects of child care quality on social adjustment.

Weak cooperativity in selected iron(II) 1D coordination polymers

Energy Technology Data Exchange (ETDEWEB)

Dirtu, Marinela M.; Gillard, Damien; Naik, Anil D. [Universite Catholique de Louvain, Institute of Condensed Matter and Nanosciences, MOST - Inorganic Chemistry (Belgium); Rotaru, Aurelian [' Stefan cel Mare' University, Department of Electrical Engineering and Computer Science (Romania); Garcia, Yann, E-mail: ann.garcia@uclouvain.be [Universite Catholique de Louvain, Institute of Condensed Matter and Nanosciences, MOST - Inorganic Chemistry (Belgium)

2012-03-15

The spin crossover behaviour of a new class of Fe{sup II} coordination polymers [Fe(phtptrz){sub 3}]I{sub 2} (1), [Fe(phtptrz){sub 3}](ReO{sub 4}){sub 2} Bullet CH{sub 3}OH (2) and [Fe(phtptrz){sub 3}]TaF{sub 7} Bullet 6H{sub 2}O (3) based on a novel ligand 4-(3{sup Prime} -N-phtalimido-propyl)-1,2,4-triazole (phtptrz), were investigated by temperature dependent {sup 57}Fe Moessbauer spectroscopy and magnetic susceptibility measurements. The adverse effect of bulky substituent on 1,2,4-triazole, favorable supramolecular interactions and influence of increasing anion size on spin crossover profile is discussed. 1 and 2 show thermally induced spin conversions of gradual and incomplete nature with associated thermochromism, and transition temperatures T{sub 1/2} {approx} 163 K and 137 K, respectively. A spin state crossover is also identified for 3.

Artifacts in MRI of the temporomandibular joint caused by dental alloys: a phantom study at 1.5 T

International Nuclear Information System (INIS)

Fellner, C.; Erlangen-Nuernberg Univ., Erlangen; Behr, M.; Fellner, F.; Held, P.; Handel, G.; Feuerbach, S.

1997-01-01

Purpose: The influence of dental alloys on MRI of the temporomandibular joint was studied using a phantom model for this joint. Methods: At 1,5 T, 15 dental alloys and 14 of their most important components were investigated acquiring sagittal (FOV: 150 mm) and transverse (FOV: 250 mm) T 1 -weighted SE additionally. The artifacts were assessed qualitatively as well as quantitatively, and the samples were subdivided into four artifact categories. Results: Ag, Cu, Ga, In, Ti, Sn, Zn, amalgan, the precious alloys, the Au-Pd and Ag-Pd alloys showed no artifacts (category I). Minimal artifacts below 10 mm on transverse images (category II) were found for Cr, Pd, Pt and for the Ni-Cr alloy. Mn and the remaining non-precious alloys induced artifacts up to 30 mm (category III). Significant artifacts - more than 30 mm - (category IV) were to be more susceptible for artifacts than T 1 -weighted SE and FLASH techniques. Conclusions: In contrast to dental alloys for fixed prosthodontics, Ni-Cr- or 18/8 wires used for orthodontic bands can influence not only the image quality, but also the diagnostic reliability of MRI of the temporomandibular joint. (orig.) [de