Sistema de control de proyectos de edificaciones multifamiliares para reducir riesgos en la fase de cierre.

El enfoque de esta investigación es cualitativo porque no fue necesaria la intervención de datos numéricos para lograr el objetivo. Actualmente, la gestión de proyectos tradicionales que se aplican en las partidas de estructuras presentan deficiencias en los procesos de diseño y ejecución que afectan al proyecto en su fase de cierre. El objetivo general de esta investigación fue proponer un sistema de control en la partida de estructuras de una edificación multifamiliar para reducir los riesgos en la fase de cierre utilizando metodologías de trabajo colaborativas, evitando así pérdidas de tiempo que afecten el cronograma de obra que a su vez puede retrasar el cierre del proyecto y generar una insatisfacción del cliente, además de los sobrecostos provocados por la pérdida de recursos. El nivel de desarrollo de esta investigación es exploratorio, además, se utilizó un diseño no experimental y una orientación aplicada con un método analítico – deductivo. La técnica que se utilizó para la variable “Sistema de control” es la entrevista y el instrumento que se utilizó para la variable “Riesgos en la fase de cierre” es el cuestionario. Seguidamente de la ejecución de la entrevista, se identificaron los riesgos que estuvieron presentes en el proyecto. Luego se analizaron y finalmente se propuso una solución aplicando el sistema de control en cada uno de estos casos con el propósito de disminuir su desarrollo en las sub-partidas dentro la fase de diseño y ejecución para que se cumpla la fase de cierr

Upregulation of 8-Lipoxygenase in the Dermatitis of IκB-α-Deficient Mice

Neonatal mice deficient in IκB-α, an inhibitor of the ubiquitous transcription factor NF-κB, develop severe and widespread dermatitis shortly after birth. In humans, inflammatory skin disorders such as psoriasis are associated with accumulation in the skin of the unusual arachidonic acid metabolite 12R-hydroxyeicosatetraenoic acid (12R-HETE), a product of the enzyme 12R-lipoxygenase. To examine the etiology of the murine IκB-α-deficient skin phenotype, we investigated the expression of lipoxygenases and the metabolism of exogenous arachidonic acid in the skin. In the IκB-α-deficient animals, the major lipoxygenase metabolite was 8S-HETE, formed together with a minor amount of 12S-HETE; 12R-HETE synthesis was undetectable. Skin from the wild-type littermates formed 12S-HETE as the almost exclusive lipoxygenase metabolite. Upregulation of 8S-lipoxygenase (8-LOX) in IκB-α-deficient mice was confirmed at the transcriptional and translational level using ribonuclease protection assay and western analysis. In immunohistochemical studies, increased expression of 8-LOX was detected in the stratum granulosum of the epidermis. In the stratum granulosum, 8-LOX may be involved in the terminal differentiation of keratinocytes. Although mouse 8S-lipoxygenase and human 12R-lipoxygenase are not ortholog genes, we speculate that in mouse and humans the two different enzymes may fulfill equivalent functions in the progression of inflammatory dermatoses

Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.National Institutes of Health (U.S.) (grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (FA9950-04-1-0079

Variably protease-sensitive prionopathy, a unique prion variant with inefficient transmission properties

Variably protease-sensitive prionopathy (VPSPr) can occur in persons of all codon 129 genotypes in the human prion protein gene (PRNP) and is characterized by a unique biochemical profile when compared with other human prion diseases. We investigated transmission properties of VPSPr by inoculating transgenic mice expressing human PRNP with brain tissue from 2 persons with the valine-homozygous (VV) and 1 with the heterozygous methionine/valine codon 129 genotype. No clinical signs or vacuolar pathology were observed in any inoculated mice. Small deposits of prion protein accumulated in the brains of inoculated mice after challenge with brain material from VV VPSPr patients. Some of these deposits resembled microplaques that occur in the brains of VPSPr patients. Comparison of these transmission properties with those of sporadic Creutzfeldt-Jakob disease in the same lines of mice indicated that VPSPr has distinct biological properties. Moreover, we established that VPSPr has limited potential for human-to-human transmission

Heterogeneous Surface Expression of EspA Translocon Filaments by Escherichia coli O157:H7 Is Controlled at the Posttranscriptional Level

Type III secretion systems of enteric bacteria enable translocation of effector proteins into host cells. Secreted proteins of verotoxigenic Escherichia coli O157 strains include components of a translocation apparatus, EspA, -B, and -D, as well as “effectors” such as the translocated intimin receptor (Tir) and the mitochondrion-associated protein (Map). This research has investigated the regulation of LEE4 translocon proteins, in particular EspA. EspA filaments could not be detected on the bacterial cell surface when E. coli O157:H7 was cultured in M9 minimal medium but were expressed from only a proportion of the bacterial population when cultured in minimal essential medium modified with 25 mM HEPES. The highest proportions of EspA-filamented bacteria were detected in late exponential phase, after which filaments were lost rapidly from the bacterial cell surface. Our previous research had shown that human and bovine E. coli O157:H7 strains exhibit marked differences in EspD secretion levels. Here it is demonstrated that the proportion of the bacterial population expressing EspA filaments was associated with the level of EspD secretion. The ability of individual bacteria to express EspA filaments was not controlled at the level of LEE1-4 operon transcription, as demonstrated by using both β-galactosidase and green fluorescent protein (GFP) promoter fusions. All bacteria, whether expressing EspA filaments or not, showed equivalent levels of GFP expression when LEE1-4 translational fusions were used. Despite this, the LEE4-espADB mRNA was more abundant from populations with a high proportion of nonsecreting bacteria (low secretors) than from populations with a high proportion of secreting and therefore filamented bacteria (high secretors). This research demonstrates that while specific environmental conditions are required to induce LEE1-4 expression, a further checkpoint exists before EspA filaments are produced on the bacterial surface and secretion of effector proteins occurs. This checkpoint in E. coli O157:H7 translocon expression is controlled by a posttranscriptional mechanism acting on LEE4-espADB mRNA. The heterogeneity in EspA filamentation could arise from phase-variable expression of regulators that control this posttranscriptional mechanism

Laser increases ATP synthesis in MEF.

<p>(A) ATP increase measured at 5 min post LLLT with wide range laser fluences and effect of mitochondrial inhibitors (sodium azide/deoxyglucose). (B) Time course of ATP increase after 0.3 J/cm2 810 nm laser. * p<0.05; ** p<0.01 compared to baseline.</p

Mitochondrial inhibitors increase ROS and NF-kB activation in MEF but reduce ATP.

<p>(A) NF-kB activation measured at 6 hours after 2 hour incubation with 100 µM inhibitors, (B) ATP levels measured after 2 hours incubation with 100- µM inhibitor. * p<0.05; ** p<0.01 compared to control. Inhibitors (100 µM) were added for 2 hours and CM-H₂DCFDA was used to measure ROS generation at 30 min (C) control, (D) antimycin A, (E) rotenone, (F) paraquat.</p