Diagnosis / Intervention criteria in damaged slabs by severe corrosion of prestressed joists

This research defines diagnosis criteria in R/C one-way slabs with severe corrosion at the lower prestressed reinforcement of the joists and proposes specific actuation criteria and constructive recommendations to increase the safety. The corrosion of this reinforcement is the most common damage in building structures, and the use of aluminous cement in the precast joists can aggravate the corrosion. The usual cases of entire residential buildings with different degrees of damage and with a few or all joists affected in a slab have been simulated. ACI-318 is used as an acceptance criterion for existing structures in the simulations, and a ratio between the ultimate load and the service load is defined as valuation coefficient. By this way, the residual safety for a damaged structure is known. Results are in accordance with the extensive experience in real intervention cases, which often still have high safety reserves.Vercher Sanchis, JM.; Gil Benso, E.; Mas Tomas, MDLA.; Lerma Elvira, C. (2013). Diagnosis / Intervention criteria in damaged slabs by severe corrosion of prestressed joists. Journal of Performance of Constructed Facilities. (04014040). doi:10.1061/(ASCE)CF.1943-5509.0000515S0401404

Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability

Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis

Arabidopsis glutathione reductase 2 is indispensable in plastids, while mitochondrial glutathione is safeguarded by additional reduction and transport systems

A highly negative glutathione redox potential (EGSH ) is maintained in the cytosol, plastids and mitochondria of plant cells to support fundamental processes, including antioxidant defence, redox regulation and iron-sulfur cluster biogenesis. Out of two glutathione reductase (GR) proteins in Arabidopsis, GR2 is predicted to be dual-targeted to plastids and mitochondria, but its differential roles in these organelles remain unclear. We dissected the role of GR2 in organelle glutathione redox homeostasis and plant development using a combination of genetic complementation and stacked mutants, biochemical activity studies, immunogold labelling and in vivo biosensing. Our data demonstrate that GR2 is dual-targeted to plastids and mitochondria, but embryo lethality of gr2 null mutants is caused specifically in plastids. Whereas lack of mitochondrial GR2 leads to a partially oxidised glutathione pool in the matrix, the ATP-binding cassette (ABC) transporter ATM3 and the mitochondrial thioredoxin system provide functional backup and maintain plant viability. We identify GR2 as essential in the plastid stroma, where it counters GSSG accumulation and developmental arrest. By contrast a functional triad of GR2, ATM3 and the thioredoxin system in the mitochondria provides resilience to excessive glutathione oxidation

Residual safety for flexural bending of slabs with corrosion in the joists

[EN] A large number of slabs with severe corrosion problems at the precast joists have appeared in Spain, often increased by the use of aluminous cement. The purpose of this paper is to evaluate the residual safety for the bending mechanisms in the most common cases of damaged slabs, to decide the magnitude of the needed intervention. The damaged slabs have been evaluated as a part of an entire building, since the boundary conditions are essential for obtaining actual behavior, taking into account the different phases of the construction process and deterioration over time. A major cracking in the constructive elements are not frequently observed in inspections, and it is found that there is a sufficient residual safety to undertake the rehabilitation works without exceptional measures.[ES] A nivel nacional han aparecido un gran número de forjados de viguetas prefabricadas con graves problemas de corrosión, potenciada en muchas ocasiones por el empleo del cemento aluminoso. El propósito de este trabajo es evaluar la seguridad residual de los mecanismos de flexión en los casos más habituales de forjados dañados, para decidir la magnitud de la intervención necesaria. Los forjados dañados se han evaluado formando parte de un edificio completo, ya que las condiciones de contorno son fundamentales para la obtención del Comportamiento real, teniendo en cuenta las distintas fases del proceso constructivo y de deterioro en el tiempo. En bastantes ocasiones en la inspección no se observa una fisuración importante en los elementos constructivos, como solados o tabiquería, y hemos comprobado que existe una seguridad residual suficiente para acometer las obras de rehabilitación sin necesidad de adoptar medidas excepcionales.Gil Benso, E.; Vercher Sanchis, JM.; Mas Tomas, MDLA.; Fenollosa Forner, EJ. (2015). Seguridad remanente a flexión en forjados con corrosión en las viguetas. Informes de la Construcción. 67(537):1-10. doi:10.3989/ic.13.084S11067537Morán Cabré, F. (1994). Estimación de la seguridad residual en estructuras de hormigón con problemas patológicos. Informes de la Construcción, 46(434), 39-51. doi:10.3989/ic.1994.v46.i434.1107(2) Giménez, E. (2007). Estudio experimental y numérico de soportes de hormigón armado reforzados con perfiles metálicos sometidos a esfuerzos de compresión simple (Tesis Doctoral). Valencia: Universidad Politécnica de Valencia.(3) Vieitez, J.A., Ramírez, J.L. (1984). Patología de la Construcción en Espa-a: Aproximación Estadística. Resumen de Tesis Doctoral. Informes de la Construcción, 36(364): 5-15.(4) Instituto Valenciano de la Edificación (IVE). (2008). Guía para la Inspección y Evaluación Preliminar de estructuras de hormigón en edificios existentes. Serie guías de la calidad. Valencia: Generalitat Valenciana - Conselleria de Medi Ambient, Aigua, Urbanisme i Habitatge.(5) Instituto Valenciano de la Edificación (IVE). (2008). Experiencia en Inspección de estructuras en edificios. Comunidad Valenciana 1991-2008. Serie guías de la calidad. Valencia: Generalitat Valenciana - Conselleria de Medi Ambient, Aigua, Urbanisme i Habitatge.(6) Grupo Espa-ol del Hormigón (GEHO). (1994). Reparación y refuerzo de estructuras hormigón. Guía FIP de buena práctica. Boletín GEHO, 14. Madrid.Evangelista, A. D., Leonardis, A. D., Valente, C., & Zuccarino, L. (2011). Design and testing of corrosion damaged prestressed concrete joists: the Pescara Benchmark. Journal of Physics: Conference Series, 305, 012081. doi:10.1088/1742-6596/305/1/012081Coronelli, D., & Gambarova, P. (2004). Structural Assessment of Corroded Reinforced Concrete Beams: Modeling Guidelines. Journal of Structural Engineering, 130(8), 1214-1224. doi:10.1061/(asce)0733-9445(2004)130:8(1214)Foster, S. ., Bailey, C. ., Burgess, I. ., & Plank, R. . (2004). Experimental behaviour of concrete floor slabs at large displacements. Engineering Structures, 26(9), 1231-1247. doi:10.1016/j.engstruct.2004.04.002(11) Ministerio de Vivienda. (2006, 28 de marzo). Código Técnico de la Edificación (CTE). Boletín Oficial del Estado, nº 74: 11816-11831. Madrid, Espa-a.(12) Bangash, M.Y.H. (1989). Concrete and concrete structures: Numerical modeling and applications. London - New York: Elsevier Applied Science.(13) Willam, K.J., Warnke, E.D. (1975). Constitutive model for the triaxial behavior of concrete. En Proceedings of the International Association for Bridge and Structural Engineering, ISMES, 19: 1-30. Bergamo, Italy.(14) Vercher, J. (2013). Seguridad residual en los forjados con corrosión severa (Tesis Doctoral). Valencia: Universidat Politècnica de València.Cubel, F., Mas, A., Vercher, J., & Gil, E. (2012). Design and construction recommendations for brick enclosures with continuous air chamber. Construction and Building Materials, 36, 151-164. doi:10.1016/j.conbuildmat.2012.04.128Brencich, A., & Felice, G. de. (2009). Brickwork under eccentric compression: Experimental results and macroscopic models. Construction and Building Materials, 23(5), 1935-1946. doi:10.1016/j.conbuildmat.2008.09.004Dilrukshi, K. G. S., Dias, W. P. S., & Rajapakse, R. K. N. D. (2010). Numerical modelling of cracks in masonry walls due to thermal movements in an overlying slab. Engineering Structures, 32(5), 1411-1422. doi:10.1016/j.engstruct.2010.01.019(18) Fanning, P. (2001). Nonlinear models of reinforced and post-tensioned concrete beams. Electronic Journal of Structural Engineering, 2: 111-119.(19) Tavio, T., Tata, A. (2009). Predicting nonlinear behavior and stress-strain relationship of rectangular confined reinforced concrete columns with Ansys. Civil Engineering Dimension, 11(1): 23-31.Rodriguez, J., Ortega, L., & Casal, J. (1997). Load carrying capacity of concrete structures with corroded reinforcement. Construction and Building Materials, 11(4), 239-248. doi:10.1016/s0950-0618(97)00043-

Overlapping variants in the blood, tissues and cell lines for patients with intracranial meningiomas are predominant in stem cell-related genes

Objective: Bulk tissue genomic analysis of meningiomas identified common somatic mutations, however, it often excluded blood-related variants. In contrast, genomic characterisation of primary cell lines that can provide critical information regarding growth and proliferation, have been rare. In our work, we identified the variants that are present in the blood, tissues and corresponding cell lines that are likely to be predictive, tumorigenic and progressive. Method: Whole-exome sequencing was used to identify variants and distinguish related pathways that exist in 42 blood, tissues and corresponding cell lines (BTCs) samples for patients with intracranial meningiomas. Conventional sequencing was used for the confirmation of variants. Integrative analysis of the gene expression for the corresponding samples was utilised for further interpretations. Results: In total, 926 BTC variants were detected, implicating 845 genes. A pathway analysis of all BTC genes with damaging variants indicated the 'cell morphogenesis involved in differentiation' stem cell-related pathway to be the most frequently affected pathway. Concordantly, five stem cell-related genes, GPRIN2, ALDH3B2, ASPN, THSD7A and SIGLEC6, showed BTC variants in at least five of the patients. Variants that were heterozygous in the blood and homozygous in the tissues or the corresponding cell lines were rare (average: 1.3 +/- 0.3%), and included variants in the RUNX2 and CCDC114 genes. An analysis comparing the variants detected only in tumours with aggressive features indicated a total of 240 BTC genes, implicating the 'homophilic cell adhesion via plasma membrane adhesion molecules' pathway, and identifying the stem cell-related transcription coactivator NCOA3/AIB1/SRC3 as the most frequent BTC gene. Further analysis of the possible impact of the poly-Q mutation present in the NCOA3 gene indicated associated deregulation of 15 genes, including the up-regulation of the stem cell related SEMA3D gene and the angiogenesis related VEGFA gene. Conclusion: Stem cell-related pathways and genes showed high prevalence in the BTC variants, and novel variants in stem cell-related genes were identified for meningioma. These variants can potentially be used as predictive, tumorigenic and progressive biomarkers for meningioma

Analysis of the residual safety level in R/C slabs with severe joist corrosion

An analysis until the failure on a series of one-way slabs with severe corrosion at the lower reinforcement of the R/C joists is presented. Different positions in the slab and number of damaged joists have been studied, obtaining the residual safety assessment in cases of slabs damaged by flexural failure mechanisms. Since the boundary conditions have proved decisive for obtaining the behavior, the damaged slab has been evaluated as part of the entire building, as precisely as possible, taking into account the different phases of the construction process and deterioration in time, and the complex behavior of concrete, steel and masonry. The results of the proposed methodology are consistent with the pathology of the observed cases. As a result of this study the authors propose practical recommendations to help in making decisions about the magnitude of the intervention, always necessary in this type of pathology.Vercher Sanchis, JM.; Gil Benso, E.; Mas Tomas, MDLA.; Cubel Arjona, FJ. (2014). Analysis of the residual safety level in R/C slabs with severe joist corrosion. Journal of Performance of Constructed Facilities. 1-14. doi:10.1061/(ASCE)CF.1943-5509.0000608S11

Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability

Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial

BACKGROUND: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. METHODS: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. FINDINGS: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. INTERPRETATION: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. FUNDING: Medical Research Council