The presence of Alkali-Silica Reaction in concrete structures and damaged caused under this reaction

The concrete structures during the life exploitations are under the severe conditions. Inthis way the different behavior of structures will be basic on the conditions. In this paper wewill present one of the important parameter, Alkali-Silica Reaction, and the damage under thisparameter in concrete components and in concrete structures. In most concrete, aggregates aremore or less chemically inert. However, some aggregates react with the alkali hydroxides inconcrete, causing expansion and cracking over a period of many years. This alkali-aggregatereaction has two forms: alkali-silica reaction (ASR) and alkali-carbonate reaction (ACR). Thefailure to fallow precautions may result in progressive degradation, demanding expensiverepair and improvement of concrete construction to preserve the prescribed function.In this state-of-the-art report we will present the concept of ASR, factors involved inASR and the means that are available to control it. Although there is extensive knowledgeabout the mechanisms of the reaction, the components of the aggregate that can reactharmfully and precautions to be taken to avoid resulting distress, gaps still exist in commonknowledge for ASR. This is partly true with respect to the applicability of test methods toidentify the potential for reactivity, methods to repair affected concrete and, means to controlthe consequences of the reactions in existing structures

Recycling aggregate from concrete, properties and possibility for using in ready Mix Concrete

Many requests for different types of concrete, in general are depends of the aggregates. One of the aim of this paper is to analyses the possibilities of using the recycling aggregate, from part of existing concrete such a raw materials and during the technological process for production of aggregate. Recycling of concrete is a relatively simple process. It involves breaking, removing, and crushing existing concrete into a material with a specified size and quality. In this paper the main target is to compare the properties of fresh concrete and the hardening concrete for the mix design with crashed aggregate and recycling aggregate from parts of concrete after the demolition process.Nowadays large amount of demolished concrete are available on construction sites which are now posing a serious problem for transport in urban areas. Day by day this amount is larger and the reasons are that:- Many old buildings, concrete sidewalks, bridges and other structures have exceeded their age limit use due to structural deterioration.- Other possible structures for use are in ruin, because they are not serving the needs of today's society.- Structures have become waste resulting from natural disasters like cyclones, earthquakes,floods etc.As a result of greater demand for concrete, taking into account the fact that aggregate isthe component with the largest participation in concrete. Decreasing the source of natural aggregate we should explore the use of recycled aggregate. Recycled aggregate has goodquality especially in resistance to pressure when the content of brick is not more than 0.5%, it presents the potential for use in a wide range of applications, for the case when it meets the test and performance requirements. However the quality of the concrete which is made with recycled aggregate is lower compared to concrete which is made with natural aggregate.Nowadays, the application of recycled aggregate in construction areas is extensive. It's application is different from country to country, in the sense that each state sets the criteriafor use depending on it's quality.Based on the experience of use, recycled aggregate can be used for: production of concrete, in concrete roads, for production of concrete domes, as padding of the embankment,for construction of pipes, production of concrete blocks etc. Almost in all cases where natural aggregate is used.Based on laboratory analysis Recycled aggregate compared with natural aggregate: absorbsmore water, it has less density in many cases, it has lower specific weight, lower resistance to abrasion, it's more easily to destroy it, it contains more dust particles etc. Due to these results to gain the desired work ability of concrete obtained from the recycled aggregate is necessaryto add a certain amount of water to saturate recycled aggregate before or during mixing with other ingredients of concrete, if not previously used any additional reducing the rate of water absorption. On the other hand it is very important to use the concrete with recycling aggregate for the concrete which offer very good properties in thermo insulation, such a very important request in efficiency of energy

Repair the old concrete parts of the Hydro Plant "LUMBARDHI" in Decan-Kosova

Request for reactivate the Hydro Plant is directly depend of the state of the accumulatewater basin. The present state of the part of concrete was critical and impossible forusing the water accumulations.The concrete parts are damage during the long period of attack from different factors.Removing and replacement of the parts of old concrete is directly in connections with the examinationsof concrete and after the proposal the new materials and methodology for repairing.In this study work we used the nondestructive and destructive methods for analyses the existingconcrete state for proposal the new materials, especially in the surface treatments

Traffic noise in urban and regional roads and impact on the administrative facility P+30 in Prishtina

Many current problems are related to noise, which in many cases may be undesirable factorfor the daily activities and work conditions. This is especially evident in urban areas, where isa rapid growth of traffic including the number of vehicles, especially in peak time.Orientations and knowledge bases for the noise will take an important place in this paper,with the right understanding of this phenomenon.Till now in our country that is not taken into account in road and urban analyses. In this paperwe will orient the potential impact of noise in the administrative building in Pristina with P+30 floors, which is very close to the roundabout as a major source of noise. Such an outputdata, based on present measurements of the number of vehicles, made in a different specifiedperiod of time according to standards, and those elements will be interlinked with othergeometric and material parameters. All the analyses will show a result of the intensity of thenoise in dB. To analyze these parameters, intensity of the noise will be taken as the workloadof analyzed building. Also the result of unwanted intensity will be the factor for the designeddimensions and the calculation of the sound barriers in the roundabout, taking into accountthe incorporation in the environment and the urban planning of that part.The result will be presented as a 3D animation for this urban part and the impact of noise asan important factor, since we are dealing with a large concentration of administration in thisbuilding

FUS and TARDBP but Not SOD1 Interact in Genetic Models of Amyotrophic Lateral Sclerosis

Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALS–related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS–related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. Conclusions These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background: Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. // Methods: The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). // Results: SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. // Conclusions: These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings

Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.

Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS