6 Field-Observed Cracking of Paired Lightweight and Normalweight Concrete Bridge Decks

Research has suggested that conventional lightweight concrete can offer durability advantages due to reduced cracking tendency. Although a number of publications exist providing the results of laboratory-based studies on the durability performance of lightweight concrete (with lightweight coarse aggregate) and internally cured concrete (using prewetted lightweight fine aggregate), far fewer field studies of durability performance of conventional lightweight concrete bridge decks in service have been performed. This study was commissioned to provide insight to a highway agency on whether enhanced durability performance, and therefore reduced maintenance and longer lifecycles, could be anticipated from existing lightweight concrete bridge decks that were not intentionally internally cured. To facilitate performance comparison, each lightweight bridge deck selected for inclusion in this study was paired with a companion normalweight bridge deck on a bridge of similar structural type, deck thickness, and geometric configuration, with similar age, traffic, and environmental exposure. The field-observed cracking of the decks was recorded and evaluated, and crack densities for transverse, longitudinal, and pattern cracking of the normalweight and lightweight deck in each pair were compared. Although some trends linking crack prevalence to geographic location, traffic, and age were observed, a distinct difference between the cracking present in the paired lightweight and normalweight bridge decks included in this study was not readily evident. Statistical analysis using analysis of covariance (ANCOVA) to adjust for age and traffic influence did not indicate that the type of concrete deck (lightweight or normalweight) is a statistically significant factor in the observed cracking. Therefore, for these service environments, lightweight decks did not consistently demonstrate reduced cracking

Employee performance, leadership style and emotional intelligence

Purpose: The purpose of this research is to explore the relationship between employee performance, leadership style and emotional intelligence in the context of a South African parastatal. Problem Investigated: There is a lack of literature and empirical research on the type of leadership required to achieve high levels of employee performance within South African parastatals. Methodology: The Multifactor Leadership Questionnaire (MLQ) was used to determine leadership style, while the Emotional Competency Profiler (ECP) was used to determine the emotional intelligence of the sample of leaders. Employee performance data was provided by the parastatal, based on their performance management system. Data was analysed using correlation analysis, multiple regression analysis, the standard regression ANOVA/F-test, t-tests and Cronbach alpha reliability coefficient. Findings: The findings of the research show that the ECP is a reliable measure of emotional intelligence and that while the MLQ is a reliable measure of transformational leadership, it is not a reliable measure of transactional leadership. The results of the correlation analysis show a positive significant relationship between emotional intelligence and transformational leadership and a negative significant relationship between employee performance and emotional intelligence. The results of regressing employee performance on emotional intelligence and transformational leadership show that emotional intelligence and transformational leadership have no significant effect on employee performance. The results of the regression models of the research could be biased by the lack of variance in employee performance data. Value of the Research: The value of the research lies in it confirming the MLQ as a reliable measure of transformational leadership and the ECP as a reliable measure of emotional intelligence. The finding of a positive significant relationship between emotional intelligence and transformational leadership is a valuable contribution to the literature. Conclusion: Although a positive significant relationship between emotional intelligence and transformational leadership was found, there is a need for further research to determine the type of leadership best suited to achieve high levels of employee performance within the parastatal

Natural history study of glycan accumulation in large animal models of GM2 gangliosidoses

beta-hexosaminidase is an enzyme responsible for the degradation of gangliosides, glycans, and other glycoconjugates containing beta-linked hexosamines that enter the lysosome. GM2 gangliosidoses, such as Tay-Sachs and Sandhoff, are lysosomal storage disorders characterized by beta-hexosaminidase deficiency and subsequent lysosomal accumulation of its substrate metabolites. These two diseases result in neurodegeneration and early mortality in children. A significant difference between these two disorders is the accumulation in Sandhoff disease of soluble oligosaccharide metabolites that derive from N- and O-linked glycans. In this paper we describe our results from a longitudinal biochemical study of a feline model of Sandhoff disease and an ovine model of Tay-Sachs disease to investigate the accumulation of GM2/GA2 gangliosides, a secondary biomarker for phospholipidosis, bis-(monoacylglycero)-phosphate, and soluble glycan metabolites in both tissue and fluid samples from both animal models. While both Sandhoff cats and Tay-Sachs sheep accumulated significant amounts of GM2 and GA2 gangliosides compared to age-matched unaffected controls, the Sandhoff cats having the more severe disease, accumulated larger amounts of gangliosides compared to Tay-Sachs sheep in their occipital lobes. For monitoring glycan metabolites, we developed a quantitative LC/MS assay for one of these free glycans in order to perform longitudinal analysis. The Sandhoff cats showed significant disease-related increases in this glycan in brain and in other matrices including urine which may provide a useful clinical tool for measuring disease severity and therapeutic efficacy. Finally, we observed age-dependent increasing accumulation for a number of analytes, especially in Sandhoff cats where glycosphingolipid, phospholipid, and glycan levels showed incremental increases at later time points without signs of peaking. This large animal natural history study for Sandhoff and Tay-Sachs is the first of its kind, providing insight into disease progression at the biochemical level. This report may help in the development and testing of new therapies to treat these disorders

Characterization of glycan substrates accumulating in GM1 Gangliosidosis

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies

A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex.

There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indicates that ERVs are the cause of reverse transcriptase activity in ALS, but it is currently unclear whether this is due to a specific ERV locus or a family of ERVs. We employed a combination of bioinformatic methods to identify whether specific ERVs or ERV families are associated with ALS. Using the largest post-mortem RNA-sequence datasets available we selectively identified ERVs that closely resembled full-length proviruses. In the discovery dataset there was one ERV locus (HML6_3p21.31c) that showed significant increased expression in post-mortem motor cortex tissue after multiple-testing correction. Using six replication post-mortem datasets we found HML6_3p21.31c was consistently upregulated in ALS in motor cortex and cerebellum tissue. In addition, HML6_3p21.31c showed significant co-expression with cytokine binding and genes involved in EBV, HTLV-1 and HIV type-1 infections. There were no significant differences in ERV family expression between ALS and controls. Our results support the hypothesis that specific ERV loci are involved in ALS pathology

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page