826 research outputs found
Benefits of current percolation in superconducting coated conductors
The critical currents of MOD/RABiTS and PLD/IBAD coated conductors have been
measured as a function of magnetic field orientation and compared to films
grown on single crystal substrates. By varying the orientation of magnetic
field applied in the plane of the film, we are able to determine the extent to
which current flow in each type of conductor is percolative. Standard
MOD/RABiTS conductors have also been compared to samples whose grain boundaries
have been doped by diffusing Ca from an overlayer. We find that undoped
MOD/RABiTS tapes have a less anisotropic in-plane field dependence than
PLD/IBAD tapes and that the uniformity of critical current as a function of
in-plane field angle is greater for MOD/RABiTS samples doped with Ca.EPSRC
US Department of Energ
Diesel Exhaust Particles Activate the Matrix-Metalloproteinase-1 Gene in Human Bronchial Epithelia in a β-ArrestinâDependent Manner via Activation of RAS
BACKGROUND: Diesel exhaust particles (DEPs) are globally relevant air pollutants that exert a detrimental human health impact. However, mechanisms of damage by DEP exposure to human respiratory health and human susceptibility factors are only partially known. Matrix metalloproteinase-1 (MMP-1) has been implied as an (etio)pathogenic factor in human lung and airway diseases such as emphysema, chronic obstructive pulmonary disease, chronic asthma, tuberculosis, and bronchial carcinoma and has been reported to be regulated by DEPs. OBJECTIVE: We elucidated the molecular mechanisms of DEPs' up-regulation of MMP-1. METHODS/RESULTS: Using permanent and primary human bronchial epithelial (HBE) cells at air-liquid interface, we show that DEPs activate the human MMP-1 gene via RAS and subsequent activation of RAF-MEK-ERK1/2 mitogen-activated protein kinase signaling, which can be scaffolded by beta-arrestins. Short interfering RNA mediated beta-arrestin1/2 knockout eliminated formation, subsequent nuclear trafficking of phosphorylated ERK1/2, and resulting MMP-1 transcriptional activation. Transcriptional regulation of the human MMP-1 promoter was strongly influenced by the presence of the -1607GG polymorphism, present in 60-80% of humans, which led to striking up-regulation of MMP-1 transcriptional activation. CONCLUSION: Our results confirm up-regulation of MMP-1 in response to DEPs in HBE and provide new mechanistic insight into how these epithelia, the first line of protection against environmental insults, up-regulate MMP-1 in response to DEP inhalation. These mechanisms include a role for the human -1607GG polymorphism as a susceptibility factor for an accentuated response, which critically depends on the ability of beta-arrestin1/2 to generate scaffolding and nuclear trafficking of phosphorylated ERK1/2
Substrate-induced band gap opening in epitaxial graphene
Graphene has shown great application potentials as the host material for next
generation electronic devices. However, despite its intriguing properties, one
of the biggest hurdles for graphene to be useful as an electronic material is
its lacking of an energy gap in the electronic spectra. This, for example,
prevents the use of graphene in making transistors. Although several proposals
have been made to open a gap in graphene's electronic spectra, they all require
complex engineering of the graphene layer. Here we show that when graphene is
epitaxially grown on the SiC substrate, a gap of ~ 0.26 is produced. This gap
decreases as the sample thickness increases and eventually approaches zero when
the number of layers exceeds four. We propose that the origin of this gap is
the breaking of sublattice symmetry owing to the graphene-substrate
interaction. We believe our results highlight a promising direction for band
gap engineering of graphene.Comment: 10 pages, 4 figures; updated reference
Autoreactive T cell profiles are altered following allogeneic islet transplantation with alemtuzumab induction and reâemerging phenotype is associated with graft function
Islet transplantation is an effective therapy for lifeâthreatening hypoglycemia, but graft function gradually declines over time in many recipients. We characterized isletâspecific T cells in recipients within an islet transplant program favoring alemtuzumab (ATZ) lymphodepleting induction and examined associations with graft function. Fiftyâeight recipients were studied: 23 pretransplant and 40 posttransplant (including 5 with pretransplant phenotyping). The proportion with isletâspecific T cell responses was not significantly different over time (preâTx: 59%; 1â6 m posttransplant: 38%; 7â12 m: 44%; 13â24 m: 47%; and >24 m: 45%). However, phenotype shifted significantly, with IFNâÎłâdominated response in the pretransplant group replaced by ILâ10âdominated response in the 1â6 m posttransplant group, reverting to predominantly IFNâÎłâoriented response in the >24 m group. Clustering analysis of posttransplant responses revealed two main agglomerations, characterized by IFNâÎł and ILâ10 phenotypes, respectively. ILâ10âoriented posttransplant response was associated with relatively low graft function. Recipients within the ILâ10+ cluster had a significant decline in Câpeptide levels in the period preceding the ILâ10 response, but stable graft function following the response. In contrast, an IFNâÎł response was associated with subsequently decreased Câpeptide. Islet transplantation favoring ATZ induction is associated with an initial altered isletâspecific T cell phenotype but reversion toward pretransplant profiles over time. Posttransplant autoreactive T cell phenotype may be a predictor of subsequent graft function
Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study
Childhood loneliness is characterised by childrenâs perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed
Prevalence of major depression in preschool children
The prevalence of preschool major depressive disorder (MDD) was studied in the community. The whole population of children between 3 and 6 years attending preschool nurseries in three areas (one urban, one rural and one suburban) in Spain (n = 1,427) were contacted. Selection was by a two-stage procedure. At stage I, the ESDM 3-6, a screening measure for preschool depression, was used to identify a sample for more intensive interviewing. Sensitivity and specificity of the cut-off point of the ESDM 3â6 had been previously tested in a pilot study (n = 229). During the first stage, 222 preschool children (15.6%) were found to be probable depressives, because they scored 27 or more, the cut-off used. At stage II, the children were interviewed and diagnosed by the consensus of two clinicians, blind to the ESDM 3-6 results. DSM-IV diagnostic criteria were used to define caseness. A total of 16 children (1.12%) met the MDD criteria. The prevalence by areas was urban 0.87%, rural 0.88%, suburban 1.43%. Sex distribution prevalence was 1:1. This study is a contribution to the scarce epidemiology of preschool depression in the community
Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes
BACKGROUND: Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFĂ1, IGFBP3) were evaluated. METHODS: Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. RESULTS: Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3â3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1â3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6â29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFĂ1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. CONCLUSION: Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of breast cancer and BRCA2 N372H and functional observations for APEX D148E ran counter to our findings of decreased risks. Due to the many comparisons, cautious interpretation and replication of these relationships are warranted
European Association for the Study of Obesity Position Statement on the Global COVID-19 Pandemic
open18openFrßhbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie JFrßhbeck, Gema; Baker, Jennifer Lyn; Busetto, Luca; Dicker, Dror; Goossens, Gijs H; Halford, Jason C G; Handjieva-Darlenska, Teodora; Hassapidou, Maria; Holm, Jens-Christian; Lehtinen-Jacks, Susanna; Mullerova, Dana; O'Malley, Grace; Sagen, Jørn V; Rutter, Harry; Salas, Ximena Ramos; Woodward, Euan; Yumuk, Volkan; Farpour-Lambert, Nathalie
'Everyday memory' impairments in autism spectrum disorders
âEveryday memoryâ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Childrenâs Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed
Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts
BACKGROUND: An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population
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