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Abstract Recent disasters have shown that the failure of columns or shear walls exposed to fire is the main cause of building collapse. The cross-sectional thermal gradient (TG) of these structures justifies the degree of their heating and also justifies their mechanical damage, but the influence of the number of heated surfaces on their TG is not well known in the literature. A numerical FE analysis was proposed for RC columns and shear walls, assuming five fire cases in terms of the number of heated sides: only the (i) smallest and (ii) largest side, (iii) two, (iv) three and (v) four sides subjected to fire for 120 min. In order to validate the FE models, full-scale specimens were tested experimentally. Based on the number of sides hated, these structures can have an FRR of more than 120 min in relation to the values proposed by the standards.

En este artículo exploramos las circunstancias que rodearon el fallido estreno de la obra de teatro Camila O’Gorman de Heraclio Fajardo en 1856 en Buenos Aires y en 1857 en Montevideo. En el contexto político en el que Buenos Aires buscaba diferenciarse tanto de la tiranía de Juan Manuel de Rosas como del gobierno de la Confederación Argentina, su autor acusó a los herederos del rosismo como responsables de operar a favor de la censura. Sin embargo, un conjunto de intereses menos evidentes surge de un corpus que recoge las voces de una diversidad de actores involucrados en el debate sobre la obra, que deriva en el de las normas e instituciones que debían regular la actividad teatral: autoridades eclesiásticas y municipales, familiares, escritores y prensa. A través del análisis del acontecimiento, pretendemos reconstruir los contextos pertinentes e interactuantes de una particular trama compuesta de tensiones preexistentes: entre clericalismo y anticlericalismo, libertad y orden, gobierno e Iglesia, presente y pasado reciente, lo público y lo privado.

Fused filament fabrication (FFF) has seen an upsurge in its utilization towards development of tailored made materials of polymer base. The advancement and diversity in fabricating the polymer composite parts by using FFF has seen the embracement of this technology in wider aspects, ranging from automotive, aerospace, construction and has marched towards day to day requirements. This research article focuses on development of polymer composite; by using flyash (FA), an industrial waste produced during coal combustion, as reinforcement in Acrylonitrile butadiene styrene (ABS) matrix, to study the physical and mechanical properties. FA, which is primarily made up of metal oxides, plays an imperative role as reinforcement. Easily and abundantly available, FA is being used in several applications to reduce the landfills utilization and also helps the environment. In this study FA was added as reinforcement in 5 and 10 wt. % respectively to ABS matrix and was developed into filament of 1.75 mm diameter. The developed ABS + FA polymer composite using FFF, were analyzed for physical and mechanical properties as per American Society for Testing and Materials (ASTM) standards. Microstructure studies were carried out for the developed composite to understand their behavior in enhancing the dimensional accuracy and tensile strength with incremental addition of FA up to 10 wt%. Tensile strength was enhanced by 28.19% and 36.13% for ABS + 5wt. % FA and ABS + 10wt. % FA respectively. Dimensional stability was also enhanced. Similarly, surface roughness analysis was carried out and it was observed to reduce with addition of FA. The surface roughness measurements provided suitable results of decrement by 9.64% and 14.6% for ABS + 5wt. % FA and ABS + 10wt. % FA respectively. Overall, the usage of FA along with FFF, has paved a path in sustainable and green technology in manufacturing.

This study presents the simulation of retrofitting measures in a residential apartment located in Sydney based on energy consumption, building characteristics, and climatic conditions through energy audits. From the results, an upgrade to a casement aluminum framed double glazing window with a thermal conductance (U-Value) of 2.3 W/m2/oC, having an initial cost of $6,570, will save 41.2 % and 21 % of the energy used for heating and cooling equipment with a simple payback of 6.3 years and fuel cost savings of $1,046. In addition, 787kWh of electricity saved from white goods by investing $1,050 has a payback of 2.2 years and fuel cost savings of $472. Finally, the building will save 2.7 tons of GHG emissions, equivalent to three people reducing energy use by 20 % in Australia. The research is vital because retrofitting multi-residential buildings in Australia has not been fully explored, leaving 7.8 million existing buildings that are not energy efficient.

Cross-laminated timber has been used in buildings since the 1990s. In the last years, there has been a growing interest in the use of this technology, especially with the adoption of the product in increasingly taller buildings. Considering that the product is manufactured from a combustible material, wood, authorities that regulate the fire safety in buildings and the scientific community have carried out numerous research and fire tests, aiming to elaborate codes which contemplate the use of cross-laminated timber in tall buildings. This paper discusses the main results obtained from the fire resistance test of a cross-laminated timber slab carried out in the horizontal gas furnace (3.0 m × 4.0 m x 1.5 m) from the University of Sao Paulo. A vertical load of 3 kN/m2 was applied over the slab and the specimens were exposed to the standard fire curve for 30 min. In addition to the 30-min test, the research also evaluated the thermal behavior of the samples during the 24 h after the burners were turned off. Throughout the test, the slab maintained the integrity and the thermal insulation, and no falling-off of the charred layer was observed. However, the 24-h test indicated that it is mandatory to consider the loss of stiffness and strength of timber caused by the thermal wave observed during the decay phase.

Abstract Glioblastoma (GBM) is the most lethal brain tumor in adults. Radiation, together with temozolomide is the standard treatment, but nevertheless, relapse occurs in nearly all cases. Understanding the mechanisms underlying radiation resistance may help to find more effective therapies. After radiation treatment, ATP is released into the tumor microenvironment where it binds and activates purinergic P2 receptors, mainly of the P2X7 subtype. Two main P2X7 splice variants, P2X7A and P2X7B, are expressed in most cell types, where they associate with distinct biochemical and functional responses. GBM cells widely differ for the level of P2X7 isoform expression and accordingly for sensitivity to stimulation with extracellular ATP (eATP). Irradiation causes a dramatic shift in P2X7 isoform expression, with the P2X7A isoform being down- and the P2X7B isoform up-modulated, as well as extensive cell death and overexpression of stemness and senescence markers. Treatment with P2X7 blockers during the post-irradiation recovery potentiated irradiation-dependent cytotoxicity, suggesting that P2X7B activation by eATP generated a trophic/growth-promoting stimulus. Altogether, these data show that P2X7A and B receptor isoform levels are inversely modulated during the post-irradiation recovery phase in GBM cells.

Comet assay provides an easy solution to estimate DNA damage in single cells through microscopy assessment. It is widely used in the analysis of genotoxic damages induced by radiotherapy or chemotherapeutic agents. DNA damage is quantified at the single-cell level by computing the displacement between the genetic material within the nucleus, typically called “comet head”, and the genetic material in the surrounding part of the cell, considered as the “comet tail”. Today, the number of works based on Comet Assay analyses is really impressive. In this work, besides revising the solutions available to obtain reproducible and reliable quantitative data, we developed an easy-to-use tool named CometAnalyser. It is designed for the analysis of both fluorescent and silver-stained wide-field microscopy images and allows to automatically segment and classify the comets, besides extracting Tail Moment and several other intensity/morphological features for performing statistical analysis. CometAnalyser is an open-source deep-learning tool. It works with Windows, Macintosh, and UNIX-based systems. Source code, standalone versions, user manual, sample images, video tutorial and further documentation are freely available at: https://sourceforge.net/p/cometanalyser.

Abstract Openings in reinforced concrete (RC) beams may be required due to building installations (electrical, water, etc.). They weaken its cross-sectional area and, in case of fire, can increase the thermal field of the structure. NBR 15200 does not consider this. The paper evaluated the influence of rectangular openings on the Fire Resistance Rating (FRR) of RC beams by the Simplified Method of NBR 15200. This method combines a non-linear thermal analysis (isotherms) with the evaluation of the flexural strength of the beams using a manual design calculation method. The thermal field were obtained by a thermal model solved by finite element analysis (FEA) with Abaqus software. Thermal parameters of NBR 15200 were used. This FRR was compared with equivalent beams without openings solved by the Tabular Method of NBR 15200. Twelve 60 cm high beams with different widths and dimensions of openings were studied. Beams with openings had a FRR up to 60 min lower than the equivalent beam without openings. The larger the size of the rectangular opening, the greater the mechanical degradation of the beam in fire. NBR 15200 Tabular Method proved to be unsafe in this case. Prescriptions for beams with openings must be shown in NBR 15200.

Abstract Background Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay. Results We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors.

Cancer immunotherapy embraces many current, promising therapeutic approaches to eradicate tumors by activating host antitumor activity [...]

Rapid urbanization significantly affects the near-surface temperature for major cities worldwide. A greater understanding of spatial-temporal changes of the near-surface temperature has given better insights into global issues such as climate change, thermal discomfort, and energy consumption. This remote sensing-based study aims to investigate the spatial-temporal variations of land surface temperature before and after the lockdown, implemented in response to the spread of COVID-19, for three major Indian cities located in different climate zones viz., i) New Delhi (inland), ii) Hyderabad (inland), and iii) Mumbai (coastal). The land surface temperature variation is assessed for 2015-2020 on different land cover types, i.e., buildings, barren land, roads, vegetation, and water. Landsat 8 OLI/TIRS images are employed to classify land use/cover types using Normalized Difference Vegetation Index, Normalized Difference Built-up Index, and Land Surface Temperature maps. Results show that for New Delhi, Hyderabad, and Mumbai, the mean land surface temperature decreases by 5°C, 1.9°C, and 0.26°C, respectively, in April 2020 (after lockdown) in comparison with April 2019. Results for Mumbai do not vary significantly compared to the other two cities. Overall, the performed analysis presents evidence of the impact produced by the COVID-19 lockdown on the surface urban heat island for different land use/cover types.

Abstract Background Acromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution. Methods This is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0. Results Median age of patients at diagnosis of acromegaly was 49.5 years (range 12–69). The median delay in diagnosis of acromegaly was 3 years (range 0.5–23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18–69). At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5–7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb. Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months. When comparing RFU between acromegalics and controls no statistically significant differences were found. Conclusions Patients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

Abstract Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.

The ecologically diverse genus Coniochaeta (Coniochaetaceae, Ascomycota) contains numerous endophytic strains that occur in healthy leaves and lichen thalli in temperate and boreal North America. These endophytes frequently represent undescribed species. Here we examine two endophytic isolates of Coniochaeta from healthy photosynthetic tissue of Platycladus orientalis (Cupressaceae), a conifer cultivated for horticultural use in Arizona, USA. On the basis of morphology, in vitro assays, phylogenetic analyses of two loci, and analyses of whole genome data, we designate these endophytes as a novel species, Coniochaeta endophytica sp. nov. Strains of C. endophytica are closely related to an isolate from a native lichen in North Carolina, which we also characterize here. We compare C. endophytica with two known species that appear to be close relatives: C. prunicola, associated with wood necrosis in stonefruit trees in South Africa, and C. cephalothecoides, isolated from soil in Asia. The new species is distinct in phylogenetic, in vitro, and whole-genome analyses from C. prunicola, and differs slightly in conidiophore morphology from that species. Although available sequence data for C. cephalothecoides are of uncertain relation to the type specimen for that species, our results support the distinctiveness of C. endophytica on the basis of morphology, perithecial formation, and phylogenetic analyses. We discuss the challenge of identifying new species in the context of fungal ecology surveys, such as those for endophytes, which often rely only on a single locus and can misidentify taxa based on their closest matches in public databases or simple comparisons of barcode sequences alone.

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics.

ABSTRACT Tumor‐induced osteomalacia (TIO) is a chronic condition associated with muscle weakness and long‐term disability. We conducted a cross‐sectional study of patients diagnosed with TIO who had been referred to our institution between May 2018 and December 2019. Our aim was to assess health‐related quality of life (HRQoL), fatigue, pain, and muscle mass and strength in these patients. Detailed information was obtained regarding general characteristics, initial symptoms and biochemical parameters measured at diagnosis and on the first visit to our institution. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐Fatigue) scale, pain using the Brief Pain Inventory–Short Form (BPI‐sf) scale and HRQoL by the 36‐item Short Form survey (SF‐36) questionnaire. Eight patients were included in the study: three without tumor localization, four with nonremission after surgery, and one with clinical recurrence 2 years after surgery. Fatigue experienced by patients with TIO was significantly higher compared to the general population (p ˂ .0001). The physical summary measure of the SF‐36 showed significantly lower values than those of the Argentinean population with chronic conditions (mean 20.4 versus 45.9, p

The concept of zero energy has emerged as the flagship for the achievement of energy conservation and CO2 emissions reduction in the built environment. The implementation of the concept beyond single buildings offers the potential of expanding the scale of zero energy performance while overcoming the limitations of single buildings related to building use, size, on-site renewable energy availability and cost. Literature to date has discussed the zero energy concept at neighborhood scale mostly by looking at theoretical and simulated cases, including both existing and new developments. All types of energy use can be considered for achieving a zero energy balance at neighborhood scale or only the building related component. Often research focuses on Renewable Energy sizing and management for achieving the balance. The present paper analyses the real data obtained from the first year of monitoring of a pilot Zero Energy Neighborhood. A comprehensive monitoring schema, with a Web-GIS monitoring platform at its core, has been developed for the measurement and verification campaign. Performance analysis has shown that the pilot neighborhood has achieved the targets set for the net regulated consumption, renewable energy production, and cost. When considering the total consumption and PV production of the neighborhood, the first five months of monitoring starting from the beginning of summer, it has achieved a positive balance. Overall, the neighborhood has achieved a positive energy balance on a yearly basis for its regulated energy needs.

En Uruguay existe un monopolio del Estado para la explotación de casinos, los cuales pueden ser desarrollados directamente por el Estado o a través de concesiones hacia los privados. Sin perjuicio de lo anterior también se desarrollan los operadores de máquinas tragamonedas clandestinas, los cuales lo realizan al margen del sistema legal, careciendo de todo tipo de autorización, control y auditorias, así como tampoco ofrecen ningún tipo de garantías a los consumidores. Además, el desarrollo de los juegos de azar ha ido evolucionando de la forma tradicional desarrollada en casinos, a nuevas modalidades de juego como el juego on-line. Esto ha tomado muchísima fuerza en aquellos países que lo han regulado de forma acorde, abriendo un nuevo abanico de opciones para el desarrollo de este tipo de juegos de azar, siendo no solo una nueva realidad para los juegos de azar, sino el futuro de la industria. Se ha planteado la discusión de si esta práctica monopólica del Estado es la apropiada, o si por el contrario se debe optar por una apertura de la misma, que sea manejada libremente por los privados y públicos, adecuando y aplicando los correspondientes mecanismos de control.

Air pollution is a major concern, particularly in developing countries. Road transport and mobile sources are considered the root causes of air pollutants. With the implementation of zero-carbon and zero-energy concepts at the district scale, cities can make great strides towards sustainable development. Urban planning schemes are moving from mere building solutions to the larger positive energy district (PED) scale. Alongside other technology systems in PEDs, increased uptake of electro-mobility solutions can play an important role in CO2 mitigation at the district level. This paper aims to quantify the exhaust emissions of six conventional and two fully hybrid vehicles using a portable emission measurement system (PEMS) in real driving conditions. The fuel consumption and exhaust pollutants of the conventional and hybrid vehicles were compared in four different urban and highway driving routes during autumn 2019 in Iran. The results showed that hybrid vehicles presented lower fuel consumption and produced relatively lower exhaust emissions. The conventional group’s fuel consumption (CO2 emissions) was 11%, 41% higher than that of the hybrids. In addition, the hybrid vehicles showed much better fuel economy in urban routes, which is beneficial for PEDs. Micro-trip analysis showed that although conventional vehicles emitted more CO2 at lower speeds, the hybrids showed a lower amount of CO2. Moreover, in conventional vehicles, NOx emissions showed an increasing trend with vehicle speed, while no decisive trend was found for NOx emissions versus vehicle speed in hybrid vehicles.

abstract: To evaluate the behavior of semi-continuous composite beams in fire, six finite elements numerical models with several steel profiles and slab dimensions were developed in ABAQUS software. The models took into account several behaviors usually suppressed in simplified analyzes such as: geometric and materials non-linearity properties and thermal expansion effects, including indirect stresses. Three support conditions were analyzed: simply supported (axial released), axial restrained and semi-continuous, totaling 18 analyzes. The different support conditions results were compared to each other and to the fire resistance time designed by simplified methods, which followed design code recommendations.

The merger of evolutionarily diverged genomes to form a new polyploid genetic system can involve extensive remodeling of gene regulation. A recent paper in BMC Biology provides important insights into regulatory events that have affected the evolution of allopolyploid cotton.

BackgroundWhole genome duplication, which results in polyploidy, is a common feature of plant populations and a recurring event in the evolution of flowering plants. Polyploidy can result in changes to gene expression and epigenetic instability. Several epigenetic phenomena, occurring at the transcriptional or post-transcriptional level, have been documented in allopolyploids (polyploids derived from species hybrids) of Arabidopsis thaliana, yet findings in autopolyploids (polyploids derived from the duplication of the genome of a single species) are limited. Here, we tested the hypothesis that an increase in ploidy enhances transgene-induced post-transcriptional gene silencing using autopolyploids of A. thaliana.Methodology/principal findingsDiploid and tetraploid individuals of four independent homozygous transgenic lines of A. thaliana transformed with chalcone synthase (CHS) inverted repeat (hairpin) constructs were generated. For each line diploids and tetraploids were compared for efficiency in post-transcriptional silencing of the endogenous CHS gene. The four lines differed substantially in their silencing efficiency. Yet, diploid and tetraploid plants derived from these plants and containing therefore identical transgene insertions showed no difference in the efficiency silencing CHS as assayed by visual scoring, anthocyanin assays and quantification of CHS mRNA.Conclusions/significanceOur results in A. thaliana indicated that there is no effect of ploidy level on transgene-induced post-transcriptional gene silencing. Our findings that post-transcriptional mechanisms were equally effective in diploids and tetraploids supports the use of transgene-driven post-transcriptional gene silencing as a useful mechanism to modify gene expression in polyploid species.

Despite the gradual decrease in incidence, gastric cancer is still the third leading cause of cancer death worldwide. Although chemotherapy enhances overall survival and quality of life in advanced disease, the median overall survival is < 12 months. In recent years, the human epidermal growth factor receptor (ErbB) family has been extensively investigated in gastric cancer. The ErbB family is composed of four closely-related members: ErbB-1 (HER1 or epidermal growth factor receptor, EGFR), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4), all of which play a critical role in regulating cell growth, proliferation and migration of tumors. It is well known that gastric cancer overexpresses HER in a heterogeneous pattern, especially EGFR, and HER2. HER3 is another important member of the ErbB family that preferentially activates the phosphatidylinositol 3-kinase (PI3K) pathway. Furthermore, its heterodimerization with HER2 seems fundamental for steering HER2-overexpressing breast cancer tumor growth. Less is known about the impact of HER4 on gastric cancer. Improved survival from the use of trastuzumab has paved the way for ErbB receptor family-targeted treatments in gastric cancer. However, unlike trastuzumab, ErbB receptor-targeted drugs have not consistently maintained the encouraging results obtained in preclinical and early clinical trials. This may be attributable to the intrinsic heterogeneity of gastric cancer and/or to the lack of standardized test quality for established biomarkers used to evaluate these biological targets. This review presents an overview of the most recent clinical studies on agents targeting the ErbB family in gastric cancer.

Introduction: Pancreatic cancer (PC) is one of the most lethal tumor worldwide, with no prognosis improvement over the past 20-years. The silent progressive nature of this neoplasia hampers the early diagnosis, and the surgical resection of the tumor, thus chemotherapy remains the only available therapeutic option. Sigma receptors (SRs) are a class of receptors proposed as new cancer therapeutic targets due to their over-expression in tumor cells and their involvement in cancer biology. The main localization of these receptors strongly suggests their potential role in ER unfolded protein response (ER-UPR), a condition frequently occurring in several pathological settings, including cancer. Our group has recently identified RC-106, a novel pan-SR modulator with good in vitro antiproliferative activities toward a panel of different cancer cell lines. In the present study, we investigated the in vitro properties and pharmacological profile of RC-106 in PC cell lines with the aim to identify a potential lead candidate for the treatment of this tumor.Methods: Pancreatic cancer cell lines Panc-1, Capan-1, and Capan-2 have been used in all experiments. S1R and TMEM97/S2R expression in PC cell lines was quantified by Real-Time qRT-PCR and Western Blot experiments. MTS assay was used to assess the antiproliferative effect of RC-106. The apoptotic properties of RC-106 was evaluated by TUNEL and caspase activation assays. GRP78/BiP, ATF4, and CHOP was quantified to evaluate ER-UPR. Proteasome activity was investigated by a specific fluorescent-based assay. Scratch wound healing assay was used to asses RC-106 effect on cell migration. In addition, we delineated the in vivo pharmacokinetic profile and pancreas distribution of RC-106 in male CD-1 mice.Results: Panc-1, Capan-1, and Capan-2 express both SRs. RC-106 exerts an antiproliferative and pro-apoptotic effect in all examined cell lines. Cells exposure to RC-106 induces the increase of the expression of ER-UPR related proteins, and the inhibition of proteasome activity. Moreover, RC-106 is able to decrease PC cell lines motility. The in vivo results show that RC-106 is more concentrated in pancreas than plasma.Conclusion: Overall, our data evidenced that the pan-SR modulator RC-106 is an optimal candidate for in vivo studies in animal models of PC.

E-cadherin is a key player in gastric cancer (GC) and germline alterations of CDH1, its encoding gene, are responsible for Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This study aimed at elucidating the role of genetic variants and DNA methylation of CDH1 promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the CDH1 gene through Next-Generation Sequencing (NGS) in a series of GC cell lines (NCI-N87, KATO-III, SNU-1, SNU-5, GK2, AKG, KKP) and the corresponding CDH1 expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of CDH1 regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC CDH1-negative patients and 6 healthy controls. The NGS analysis on CDH1 coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. CDH1 regulatory regions showed different methylation patterns in patients and controls, GC cell lines and GC tissues, expressing different E-cadherin levels. Our results showed that alterations in terms of genetic variants and DNA methylation patterns of both promoter and enhancers are associated with CDH1 expression levels and have a role in its regulation.

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In this paper, the impact that the use of simplified methods of determining temperatures evolution can produce in the stud connection resistance at elevated temperatures, in protected and unprotected composite beams, is evaluated. For this, comparisons between the obtained resistance when the temperatureis determined in the steel beam by simplifi ed methods and when it is obtained by finite elements method are carried out. It can be demonstrated that when the temperature is determined by the simplified method and the upper flange of the profi le presents a high section factor, it is overestimated in greatmeasure the resistance of the connection. This becomes more marked when in the design expressions the failure of the steel prevails.

The contribution of epigenetic variation to phenotypic variation is unclear. Imprinted genes, because of their strong association with epigenetic modifications, represent an opportunity for the discovery of such phenomena. In mammals and flowering plants, a subset of genes are expressed from only one parental allele in a process called gene imprinting. Imprinting is associated with differential DNA methylation and chromatin modifications between parental alleles. In flowering plants imprinting occurs in a seed tissue - endosperm. Proper endosperm development is essential for the production of viable seeds. We previously showed that in Arabidopsis thaliana intraspecific imprinting variation is correlated with naturally occurring DNA methylation polymorphisms. Here, we investigated the mechanisms and function of allele-specific imprinting of the class IV homeodomain leucine zipper (HD-ZIP) transcription factor HDG3. In imprinted strains, HDG3 is expressed primarily from the methylated paternally inherited allele. We manipulated the methylation state of endogenous HDG3 in a non-imprinted strain and demonstrated that methylation of a proximal transposable element is sufficient to promote HDG3 expression and imprinting. Gain of HDG3 imprinting was associated with earlier endosperm cellularization and changes in seed weight. These results indicate that epigenetic variation alone is sufficient to explain imprinting variation and demonstrate that epialleles can underlie variation in seed development phenotypes.

Despite the interest aroused by sigma receptors (SRs) in the area of oncology, their role in tumor biology remains enigmatic. The predominant subcellular localization and main site of activity of SRs are the endoplasmic reticulum (ER). Current literature data, including recent findings on the sigma 2 receptor subtype (S2R) identity, suggest that SRs may play a role as ER stress gatekeepers. Although SR endogenous ligands are still unknown, a wide series of structurally unrelated compounds able to bind SRs have been identified. Currently, the identification of novel antiproliferative molecules acting via SR interaction is a challenging task for both academia and industry, as shown by the fact that novel anticancer drugs targeting SRs are in the preclinical-stage pipeline of pharmaceutical companies (i.e., Anavex Corp. and Accuronix). So far, no clinically available anticancer drugs targeting SRs are still available. The present review focuses literature advancements and provides a state-of-the-art overview of SRs, with emphasis on their involvement in cancer biology and on the role of SR modulators as anticancer agents. Findings from preclinical studies on novel anticancer drugs targeting SRs are presented in brief.

En el trabajo se realiza el aná lisis térmico del ensayo push-ou t de conexiones tipo canal en estructuras compuestas acero – co ncreto a elevadas temperaturas a partir d e resultados numéricos generado s por el programa SuperTempcalc. El estudio se realiza para dos alternativas: vigas sin revestimie nto contra incendio y vigas r evestidas. Se proponen las temperaturas a considerar en el conc reto para determinar los factores de reduc ción de su resistencia y se val ora el impacto de estos resultados en la determinación de la re sistencia de la conexión. Finalmente, se propone un método simplificado para de terminar la resistencia de la conexión, que considera temperatu ras en el concreto definidas a través del análisis térmico y es coherente con las expresiones de cálculo de la resistencia de las conexi ones tipo canal a temperatura ambiente y con la formulación para conexiones tip o perno a elevada s temperaturas vigente en la literatura intern acional.

En este trabajo se propusieron dos métodos, uno simplificado y otro gráfico alternativo para el diseño de la conexión mecánica tipo canal en vigas compuestas de hormigón y acero en situación de incendio, a partir del estudio de su comportamiento. Se utilizó como herramienta la modelación numérica. El método simplificado desarrollado considera temperaturas definidas a través de la modelación térmica del ensayo push-out en situación de incendio y es coherente con las expresiones de diseño de las conexiones mecánicas tipo canal a temperatura ambiente y la formulación existente para el diseño de las conexiones tipo perno a elevadas temperaturas. El método gráfico alternativopropuesto constituye una opción que permite obtener de una forma directa y rápida, la resistencia a elevadas temperaturas de la conexión mecánica tipo canal para un tiempo de resistencia al fuego, en función de su resistencia a temperatura ambiente.Palabras claves: conexión mecánica tipo canal, método simplificado, método gráfico alternativo, modelación numérica, incendio._______________________________________________________________________________AbstractIn this paper two methods to design of channel mechanical connection are proposed, a simplified one and graphical alternative another, both using the numerical analysis for the study of the mechanical connection behavior. The developed simplified method considers temperatures defined through thethermal modelling of the push-out test in fire and it is coherent with the design expressions of the channel mechanical connections to ambient temperature, and the current formulation for the design of the stud connections al elevated temperatures. The proposed alternative graphical method constitutes an option that allows obtaining, in a direct and quick way, the resistance to elevatedtemperatures of the channel mechanical connections for a determined time of resistance to the fire, according to its resistance to ambient temperature.Key words: channel mechanical connection, simplified method, alternative graphical method, numerical model, fire.

India accounts for six per cent of the world’s primary energy consumption. Rapid urbanization and rapid urban population growth have had a serious impact on energy consumption and subsequent carbon emissions. In particular, cities face a complex and interrelated set of challenges across different sectors (building environment, mobility, water and waste management and public services). Re-examining these challenges by integrating smart energy management (SEM) principles is critical for sustainable and low-carbon urban development. In addition, managing energy footprint is one of the most challenging goals for cities, and as existing cities evolve and transform into smart cities, SEM becomes an integral part of the urban transformation. This article comprehensively reviews the different SEM technologies for different sectors (construction, transportation, public services, water and waste), the policies, and the current challenges and opportunities for SEM policy governance in India. Making urban energy smart can manage a city’s energy footprint and have a positive impact on future carbon emissions.

This study aimed to evaluate the effects of a multidisciplinary intervention program on the factors: stage of behavior change (SBC), physical self-description (PSD), blood pressure (BP) and physical fitness in obese adolescents. The study was characterized as quasi-experimental type, with 33 adolescents who were evaluated before and after 16 weeks of intervention. The anthropometric and fitness variables, BP were assessed, and we also applied the Stage of Change instrument and PSDQ (Physical Self-Description Questionnaire), in order to measure the SBC and the PSD, respectively. The statistical analysis involved measures of central tendency and dispersion, and the comparison between the initial and final periods was performed by Student’s t-test. The comparison between the periods before and after-intervention presented significant differences (p < 0.05) for almost all variables, except for the hip circumference, waist to hip ratio and pull-ups in the adapted bar. The program promoted effective changes in the fat consumption, and habitual physical activity and PSD of habitual physical activity, body fat and appearance. The results are quite promising and evidence the needto expand programs like this, in order to lead to the behavioral change. In this way, the physical education professional has a decisive role on this process.