State of the art on Timber Concrete Composite floor

Interest in timber-concrete composite (TCC) floors has increased over the last 20-30 years. Since the 1990âs, TCC solution is seen as a viable and effective alternative to conventional reinforced concrete and/or traditional timber floors in multistorey buildings. In TCC technology, a timber beam, either solid wood, glued laminated or laminated veneer lumber (LVL), is connected to a concrete slab using a connection system that resists shear forces and impedes slip between the members of the composite section. The strength, stiffness, location and number of connectors play a crucial role for the composite action and determine the structural and serviceability performance of the floor system. This paper discusses the state of the art of TCC structures. It presents a comprehensive review of the literature about the development and structural behaviour of TCC structures. The review addresses construction aspects and shear connection concepts. It evaluates experimental tests, finite element and numerical models. It discusses the influence of concrete elements. As recommendations, the best types of shear connection for cast in-situ and prefabricated TCC floors are put forward and assessed for criteria such as strength, stiffness, ductility and ease of manufacturing. Furthermore the most relevant numerical models are introduced. These models can be used to further the experimental results in parameters such as connections, configurations, geometrical and material properties

The predictive model for strength of inclined screws as shear connection in timber-concrete composite floor

Interest in timber-concrete composite (TCC) floors has increased over the last 30 years. TCC technology relies on timber and concrete members acting compositely together. Both timber and concrete exhibit a quite brittle behaviour in bending/tension and compression respectively whilst the shear connection is identified as the only contributor of ductile behaviour. Therefore, the strength, stiffness and arrangement of the shear connection play a crucial role in the structural design of TCC. There are only few investigations on analytical closed-form equation to predict the stiffness and strength of TCC joints as input values to design a partially composite floor. For example, Johansen's yield theory was adopted as European yield model in Eurocode 5. However, the equations are limited to vertically inserted dowels or screws and Eurocode 5 recommends that the strength and stiffness of unconventional joints should be determined by push-out tests. Previous investigations reported that the inclined shear connector significantly increase the initial stiffness and ultimate strength of the TCC joints and consequently composite floor. This paper presents a model for the strength ofTCC joint using crossed (±45°) proprietary screws (SFS Intec). The Johansen yield theory is extended to derive the strenght model of TCC joint with crossed (±45°) screws which are loaded in tension and compression. The model is an upper bound plastic collapse model that assumes the behaviour of timber and screw perfectly plastic with undamaged concrete. The failure modes considers of yield of screw, in tension or shear, and some combined modes assuming screw withdrawal, lateral crushing of the timber and the development of plastic hinges in the screw. The experimental aspect of the research consists of push-out tests and aims to verify the strength model of TCC joints with inclined screws. The failure modes are also investigated. The model seems to be reasonably accurate in predicting both the characteristic strength and failure mode. This research suggests the model to facilitate the design of inclined screw shear connections for TCC construction. © 2013 Taylor & Francis Group

NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration

<p>Abstract</p> <p>Background</p> <p>Activation of microglia causes the production of proinflammatory factors and upregulation of NADPH oxidase (NOX) that form reactive oxygen species (ROS) that lead to neurodegeneration. Previously, we reported that 10 daily doses of ethanol treatment induced innate immune genes in brain. In the present study, we investigate the effects of chronic ethanol on activation of NOX and release of ROS, and their contribution to ethanol neurotoxicity.</p> <p>Methods</p> <p>Male C57BL/6 and NF-κB enhanced GFP mice were treated intragastrically with water or ethanol (5 g/kg, i.g., 25% ethanol w/v) daily for 10 days. The effects of chronic ethanol on cell death markers (activated caspase-3 and Fluoro-Jade B), microglial morphology, NOX, ROS and NF-κB were examined using real-time PCR, immunohistochemistry and hydroethidine histochemistry. Also, Fluoro-Jade B staining and NOX gp91^phoximmunohistochemistry were performed in the orbitofrontal cortex (OFC) of human postmortem alcoholic brain and human moderate drinking control brain.</p> <p>Results</p> <p>Ethanol treatment of C57BL/6 mice showed increased markers of neuronal death: activated caspase-3 and Fluoro-Jade B positive staining with Neu-N (a neuronal marker) labeling in cortex and dentate gyrus. The OFC of human post-mortem alcoholic brain also showed significantly more Fluoro-Jade B positive cells colocalized with Neu-N, a neuronal marker, compared to the OFC of human moderate drinking control brain, suggesting increased neuronal death in the OFC of human alcoholic brain. Iba1 and GFAP immunohistochemistry showed activated morphology of microglia and astrocytes in ethanol-treated mouse brain. Ethanol treatment increased NF-κB transcription and increased NOX gp91^phoxat 24 hr after the last ethanol treatment that remained elevated at 1 week. The OFC of human postmortem alcoholic brain also had significant increases in the number of gp91^phox+ immunoreactive (IR) cells that are colocalized with neuronal, microglial and astrocyte markers. In mouse brain ethanol increased gp91^phoxexpression coincided with increased production of O₂^-and O₂^-- derived oxidants. Diphenyleneiodonium (DPI), a NOX inhibitor, reduced markers of neurodegeneration, ROS and microglial activation.</p> <p>Conclusions</p> <p>Ethanol activation of microglia and astrocytes, induction of NOX and production of ROS contribute to chronic ethanol-induced neurotoxicity. NOX-ROS and NF-κB signaling pathways play important roles in chronic ethanol-induced neuroinflammation and neurodegeneration.</p

Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood

Excessive alcohol consumption is prevalent among adolescents and may result in lasting neurobehavioral consequences. The use of animal models to study adolescent alcohol exposure has the advantage of allowing for the control necessary in order to evaluate the effects of ethanol on the brain and separate such effects from genetic background and other environmental insults. In the present study the effects of moderate ethanol vapor exposure, during adolescence, on measures of neurogenesis and behavioral measures were evaluated at two different times following ethanol withdrawal, in adulthood. The two groups of Wistar rats were both exposed to intermittent ethanol vapor (14 hrs on/10 hrs off/day) for 35–36 days from PD 23-PD 58 (average blood ethanol concentration (BEC): 163 mg%). In the first group, after rats were withdrawal from vapor they were subsequently assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test and then sacrificed at 72 days of age. The second group of rats were withdrawn from vapor and injected for 5 days with Bromo-deoxy-Uridine (BrdU). Over the next 8 weeks they were also assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test and then sacrificed at 113/114 days of age. All rats were perfused for histochemical analyses. Ethanol vapor exposed rats displayed hypoactivity in tests of locomotion and less anxiety-like and/or more “disinhibitory” behavior in the open field conflict. Quantitative analyses of immunoreactivity revealed a significant reduction in measures of neurogenesis, progenitor proliferation, as indexed by doublecortin (DCX), Ki67, and increased markers of cell death as indexed by cleaved caspase-3, and Fluoro-Jade at 72 days, and decreases in doublecortin (DCX), and increases in cleaved caspase-3 at 114 days in the ethanol vapor exposed rats. Progenitor survival, as assessed by BrdU+, was reduced in the vapor exposed animals that were sacrificed at 114 days. The reduction seen in DCX labeled in cell counts was significantly correlated with hypoactivity at 24 hours after withdrawal as well as less anxiety-like and/or more “disinhibitory” behavior in the open field conflict test at 2 and 8 weeks following termination of vapor exposure. These studies demonstrate that behavioral measures of disinhibitory behavior correlated with decreases in neurogenesis are all significantly and persistently impacted by periadolescent ethanol exposure and withdrawal in Wistar rats

Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort

Cocoa flavanols (CF) positively influence physiological processes in ways that suggest their consumption may improve aspects of cognitive function. This study investigated the acute cognitive and subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a three-day washout between drinks. Assessments included the state anxiety inventory and repeated 10-min cycles of a Cognitive Demand Battery comprising of two serial subtraction tasks (Serial Threes and Serial Sevens), a Rapid Visual Information Processing (RVIP) task and a mental fatigue scale, over the course of 1 h. Consumption of both 520 mg and 994 mg CF significantly improved Serial Threes performance. The 994 mg CF beverage significantly speeded RVIP responses but also resulted in more errors during Serial Sevens. Increases in self-reported mental fatigue were significantly attenuated by the consumption of the 520 mg CF beverage only. This is the first report of acute cognitive improvements following CF consumption in healthy adults. While the mechanisms underlying the effects are unknown they may be related to known effects of CF on endothelial function and blood flow

Periadolescent ethanol exposure reduces adult forebrain ChAT+IR neurons: correlation with behavioral pathology

Substance abuse typically begins in adolescence; therefore, the impact of alcohol during this critical time in brain development is of particular importance. Epidemiological data indicate that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences. Loss of cholinergic input to the forebrain has been demonstrated following fetal alcohol exposure and in adults with Wernicke-Korsakoff syndrome. In the present study, immunohistochemistry for choline acetyltransferase (ChAT) was determined to assess forebrain cholinergic neurons (Ch1–4), and behavioral changes following periadolescent alcohol exposure. Wistar rats were exposed to intermittent ethanol vapor (14 hrs on/10 hrs off/day) for 35 days from PD 22-PD 57 (average blood alcohol concentration (BAC): 163 mg%). Rats were withdrawn from vapor and assessed for locomotor activity, startle response, conflict behavior in the open field, and immobility in the forced swim test, as adults. Rats were then sacrificed at day 71/72 and perfused for histochemical analyses. Ethanol vapor exposed rats displayed: increased locomotor activity 8 hrs after the termination of vapor delivery for that 24 hr period at day 10 and day 20 of alcohol vapor exposure, significant reductions in the amplitude of their responses to prepulse stimuli during the startle paradigm at 24 hrs withdrawal, and at two weeks following withdrawal, less anxiety-like and/or more “disinhibitory” behavior in the open field conflict, and more immobility in the forced swim test. Quantitative analyses of ChAT immunoreactivity revealed a significant reduction in cell counts in the Ch1–2 and Ch3–4 regions of the basal forebrain in ethanol vapor exposed rats. This reduction in cell counts was significantly correlated with less anxiety-like and/or more “disinhibitory” behavior in the open field conflict test. These studies demonstrate that behavioral measures of arousal, affective state, disinhibitory behavior and ChAT+IR, are all significantly impacted by periadolescent ethanol exposure and withdrawal in Wistar rats

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10–7 and 1.16 x 10–6], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors

Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS/ELSD libraries.

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E\u27 (13) and F\u27 (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship (SAR) studies. The activity patterns observed for bengamide A (6), B (7), E (8), F (9), LAF 389 (12) and 13-14 gave rise to the following observations and conclusions. Compounds 6 and 7 display potent inhibition of NF-κB (at 80 and 90 nM, respectively) without cytotoxicity to RAW264.7 macrophage immune cells. Western blot and qPCR analysis indicated that 6 and 7 reduce the phosphorylation of IκBα and the LPS-induced expression of the pro-inflammatory cytokines/chemokines TNFα, IL-6 and MCP-1 but do not effect NO production or the expression of iNOS. These results suggest that the bengamides may serve as therapeutic leads for the treatment of diseases involving inflammation, that their anti-tumor activity can in part be attributed to their ability to serve as immune modulating agents, and that their therapeutic potential against cancer merits further consideration

A Chemical and Genetic Approach to the Mode of Action of Fumagillin

SummaryPrevious mode of action studies identified methionine aminopeptidase 2 (MetAP-2) as the target of the antiangiogenic natural product fumagillin and its drug candidate analog, TNP-470. We report here that TNP-470-mediated MetAP-2 inhibition blocks noncanonical Wnt signaling, which plays a critical role in development, cell differentiation, and tumorigenesis. Consistent with this finding, antisense MetAP-2 morpholino oligonucleotide injection in zebrafish embryos phenocopies gastrulation defects seen in noncanonical Wnt5 loss-of-function zebrafish mutants. MetAP-2 inhibition or depletion blocks signaling downstream of the Wnt receptor Frizzled, but upstream of Calmodulin-dependent Kinase II, RhoA, and c-Jun N-terminal Kinase. Moreover, we demonstrate that TNP-470 does not block the canonical Wnt/β-catenin pathway. Thus, TNP-470 selectively regulates noncanonical over canonical Wnt signaling and provides a unique means to explore and dissect the biological systems mediated by these pathways

Power Versus Affiliation in Political Ideology

Posited motivational differences between liberals and conservatives have historically been controversial. This motivational interface has recently been bridged, but the vast majority of studies have used self-reports of values or motivation. Instead, the present four studies investigated whether two classic social motive themes—power and affiliation—vary by political ideology in objective linguistic analysis terms. Study 1 found that posts to liberal chat rooms scored higher in standardized affiliation than power, whereas the reverse was true of posts to conservative chat rooms. Study 2 replicated this pattern in the context of materials posted to liberal versus conservative political news websites. Studies 3 and 4, finally, replicated a similar interactive (ideology by motive type) pattern in State of the State and State of the Union addresses. Differences in political ideology, these results suggest, are marked by, and likely reflective of, mind-sets favoring affiliation (liberal) or power (conservative). </jats:p