Experimental study of the material and bond properties of frost-damaged concrete

In an extensive experimental investigation, several types of tests were conducted on a reference specimen and frost-damaged concrete. Two levels of internal frost damage were quantified by the relative dynamic modulus of elasticity and compressive strength. Test results showed a significant influence of freeze-thaw cycles on the compressive strength and even more influence on the modulus of elasticity and the compressive strain at peak stress. Reduced tensile strength and increased fracture energy were measured. From inverse analysis of wedge splitting test results, a significant effect of frost on the shape of the tensile stress-crack opening relationship was observed: tensile strength was reduced, while the post-peak behaviour was more ductile for the frost-damaged concrete. Pull-out tests showed the influence of freeze-thaw cycles on bond strength and slip. The pull-out test results are compared with similar tests available in the literature and the effect of frost on bond behaviour is discussed

QuickSNP: an automated web server for selection of tagSNPs

Although large-scale genetic association studies involving hundreds to thousands of SNPs have become feasible, the associated cost is substantial. Even with the increased efficiency introduced by the use of tagSNPs, researchers are often seeking ways to maximize resource utilization given a set of SNP-based gene-mapping goals. We have developed a web server named QuickSNP in order to provide cost-effective selection of SNPs, and to fill in some of the gaps in existing SNP selection tools. One useful feature of QuickSNP is the option to select only gene-centric SNPs from a chromosomal region in an automated fashion. Other useful features include automated selection of coding non-synonymous SNPs, SNP filtering based on inter-SNP distances and information regarding the availability of genotyping assays for SNPs and whether they are present on whole genome chips. The program produces user-friendly summary tables and results, and a link to a UCSC Genome Browser track illustrating the position of the selected tagSNPs in relation to genes and other genomic features. We hope the unique combination of features of this server will be useful for researchers aiming to select markers for their genotyping studies. The server is freely available and can be accessed at the URL http://bioinformoodics.jhmi.edu/quickSNP.pl

APOε2 and Education in Cognitively Normal Older Subjects with High Levels of AD Pathology at Autopsy: Findings from the Nun Study

Asymptomatic Alzheimer\u27s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p \u3c 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p \u3c 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology

Influence of frost on the bond between steel and concrete

One of the severe types of deterioration in concrete structures is associated with the volume expansion of concrete caused by freezing and thawing of concrete. Frost damage in concrete is caused by the volume expansion of freezing water in the concrete pore system. Thereby, tensile stresses are initiated and micro and macro-cracks are introduced into the concrete body, which leads to a type of severe damage known as internal frost damage. This mechanism not only affects the material properties of concrete such as tensile and compressive strength and elastic modulus of concrete, but also, influences the bond strength between the reinforcement and surrounding concrete in damaged regions

Influence of frost on the bond between steel and concrete

One of the severe types of deterioration in concrete structures is associated with the volume expansion of concrete caused by freezing and thawing of concrete. Frost damage in concrete is caused by the volume expansion of freezing water in the concrete pore system. Thereby, tensile stresses are initiated and micro and macro-cracks are introduced into the concrete body, which leads to a type of severe damage known as internal frost damage. This mechanism not only affects the material properties of concrete such as tensile and compressive strength and elastic modulus of concrete, but also, influences the bond strength between the reinforcement and surrounding concrete in damaged regions

Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

OBJECTIVE: Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder. METHODS: We analyzed 644 bipolar families ascertained by the National Institute of Mental Health Human Genetics Initiative for bipolar disorder. The families have been genotyped with microsatellite loci spaced every approximately 10 cM or less across the genome. Earlier analyses of these pedigrees have been limited to nonparametric (model-free) methods and thus, information from unaffected subjects with genotypes was not considered. In this study, we used parametric analyses assuming dominant and recessive transmission and specifying a maximum penetrance of 70%, so that information from unaffecteds could be weighed in the linkage analyses. As in previous linkage analyses of these pedigrees, we analyzed three diagnostic categories: model 1 included only bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately 4% were schizoaffective, bipolar); model 2 included all individuals in model 1 plus bipolar II patients (1764 total individuals); and model 3 included all individuals in model 2 with the addition of patients with recurrent major depressive disorder (2046 total persons). RESULTS: Assuming dominant inheritance the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with D16S749 using model 2 patients. Multipoint analyses of this region yielded a maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20 markers were positive and multipoint analyses of the area gave a maximum LOD of 3.0 with model 2 cases. CONCLUSION: The chromosome 16p and 20 regions have been implicated by some studies and the data reported herein provide additional suggestive evidence of bipolar susceptibility genes in these regions

Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder

Bipolar disorder is an often-severe mental health condition characterized by alternation between extreme mood states of mania and depression. Despite strong heritability and the recent identification of 64 common variant risk loci of small effect, pathophysiological mechanisms remain unknown. Here, we analyzed genome sequences from 41 multiply-affected pedigrees and identified variants in 741 genes with nominally significant linkage or association with bipolar disorder. These 741 genes overlapped known risk genes for neurodevelopmental disorders and clustered within gene networks enriched for synaptic and nuclear functions. The top variant in this analysis - prioritized by statistical association, predicted deleteriousness, and network centrality - was a missense variant in the gene encoding D-amino acid oxidase (DAOG131V). Heterologous expression of DAOG131V in human cells resulted in decreased DAO protein abundance and enzymatic activity. In a knock-in mouse model of DAOG131, DaoG130V/+, we similarly found decreased DAO protein abundance in hindbrain regions, as well as enhanced stress susceptibility and blunted behavioral responses to pharmacological inhibition of N-methyl-D-aspartate receptors (NMDARs). RNA sequencing of cerebellar tissue revealed that DaoG130V resulted in decreased expression of two gene networks that are enriched for synaptic functions and for genes expressed, respectively, in Purkinje neurons or granule neurons. These gene networks were also down-regulated in the cerebellum of patients with bipolar disorder compared to healthy controls and were enriched for additional rare variants associated with bipolar disorder risk. These findings implicate dysregulation of NMDAR signaling and of gene expression in cerebellar neurons in bipolar disorder pathophysiology and provide insight into its genetic architecture