Problem-Solving Base Building under Uncertainty and Ambiguity: Multiple-Case Study on an Airport Expansion Program

This multiple-case study induces alternative strategies to coordinate the overlap of tasks to detail and physically execute base building with tasks to conceptualize the business-critical fit out. Base-building subsystems provide service space for occupancy, whereas fit-out subsystems make the space functional. Our empirical findings on problem-solving base-building design under uncertainty and ambiguity stem from a number of projects in an airport expansion program. They suggest that base-building subsystems show low sensitivity to incremental changes in fit out as their definitions are seldom optimized to eliminate slack. Yet, base-building subsystems show high sensitivity to radical changes in fit out when the architectures of the two subsystems are integral to one another. Three strategies for problem-solving base building stand out: (1) iterate design when preliminary information about fit out is ambiguous, or precise but unstable; (2) physically decouple the architectures of base building and fit out; and (3) design buffers in base building when preliminary information about fit out lacks precision but it is not ambiguous. These buffers can be designed out if uncertainties in fit out resolve favorably before starting the physical execution for base building.     

Mild and neutral deprotections catalyzed by cerium(IV) ammonium nitrate

The development of a novel, chemoselective, and catalytic deprotection methodology that proceeds under mild and neutral conditions is described, and its mechanism of action is analyzed in some detail. The scope, limitations, and advantages of this protocol are discussed. Selected applications in synthesis are also highlighted.     

The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells

Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.     

Highlighting Immune System and Stress in Major Depressive Disorder,Parkinson’s,and Alzheimer’s Diseases,with a Connection with Serotonin

There is recognition that both stress and immune responses are important factors in a variety of neurological disorders. Moreover, there is an important role of several neurotransmitters that connect these factors to several neurological diseases, with a special focus in this paper on serotonin. Accordingly, it is known that imbalances in stressors can promote a variety of neuropsychiatric or neurodegenerative pathologies. Here, we discuss some facts that link major depressive disorder, Alzheimer’s, and Parkinson’s to the stress and immune responses, as well as the connection between these responses and serotonergic signaling. These are important topics of investigation which may lead to new or better treatments, improving the life quality of patients that suffer from these conditions.     

Absorption of anthocyanins through intestinal epithelial cells – Putative involvement of GLUT2

Anthocyanins bioavailability is a major issue regarding their biological effects and remains unclear due to few data available on this matter. This work aimed to evaluate the absorption of anthocyanins at the intestine using Caco‐2 cells. Anthocyanin extract, rich in malvidin‐3‐glucoside, was obtained from red grape skins and tested on Caco‐2 cells. The absorption of anthocyanins, in absence or presence of 1% ethanol, was detected by HPLC/DAD/LC‐MS. Our results showed that this transport was significantly increased in the presence of ethanol especially after 60 min of incubation. In addition, cells that were pretreated for 96 h with anthocyanins (200 μg/mL) showed an increase of their own transport (about 50% increase). Expression of glucose transporters sodium‐dependent glucose transporter 1, facilitative glucose transporters 5, and facilitative glucose transporters 2 was assessed by RT‐PCR. It was found that facilitative glucose transporters 2 expression was increased (60%) in Caco‐2 cells pretreated with anthocyanins, by comparison with controls. When the effect of anthocyanin extract on ³H‐2‐deoxy‐D ‐glucose uptake was tested, an inhibitory effect was observed (about 60% decrease). However, the malvidin aglycone was tested and had no effect. In conclusion, anthocyanins could be absorbed through Caco‐2 cells, and can interfere with their own transport and also with glucose intestinal uptake.     

Effects of genetic polymorphisms at the growth hormone gene on milk yield in Serra da Estrela sheep

The five exons and the 5' and 3'-untranslated regions (5'-UTR and 3'-UTR) of the oGH gene were screened for mutations using PCR-single strand conformation polymorphism (PCR-SSCP) procedures in 523 Serra da Estrela ewes and were found to be highly polymorphic. The region extending across and between the GH2-N and GH2-Z copies was sequenced allowing the design of primers for the specific PCR amplification of each copy. These were cloned and sequenced in 20 animals representative of all SSCP patterns. The corresponding genotypes were established for each copy following nucleotide sequencing of SSCP alleles. Twenty-four polymorphic sites were found at the GH2-N (or GH1) and fourteen at the GH2-Z copies. Eight amino acid substitutions were predicted at the GH2-N and six at the GH2-Z copies. Milk yield adjusted to 150 lactation days was analysed for the genotype of each oGH gene copy taken separately or together (associated genotypes) by restricted maximum likelihood (REML) through a univariate best linear unbiased prediction (BLUP) animal model with repeated measures. Significant associations between genotypes and milk yield were observed. Within GH2-N genotypes there was a milk yield differential of 21.4+/-0.2 l/150 d between the most (N7) and the least (N5) productive ones. Within GH2-Z genotypes there was a differential of 21.6+/-0.2 l/150 d between the most (Z8) and the least (Z1) productive ones. The effect of associated GH2-N and GH2-Z genotypes revealed a differential of 39.6+/-0.3 l/150 d between the most (N1+Z7) and the least (N3+Z2) productive associated genotypes. The results show that GH2-N and GH2-Z genotypes significantly affect milk yield in Serra da Estrela ewes. Moreover, the apparent joint effect of GH2-N and GH2-Z genotype could improve milk yield in 25% as compared with the mean milk production of the analysed population.     

Electron tunneling through ultrathin boron nitride crystalline barriers

We investigate the electronic properties of ultrathin hexagonal boron nitride (h-BN) crystalline layers with different conducting materials (graphite, graphene, and gold) on either side of the barrier layer. The tunnel current depends exponentially on the number of h-BN atomic layers, down to a monolayer thickness. Conductive atomic force microscopy scans across h-BN terraces of different thickness reveal a high level of uniformity in the tunnel current. Our results demonstrate that atomically thin h-BN acts as a defect-free dielectric with a high breakdown field. It offers great potential for applications in tunnel devices and in field-effect transistors with a high carrier density in the conducting channel.     

The European debate on rate systems in the interwar period

This article describes a particular branch that evolved in the diffusion of electrical rate systems in twentieth-century Europe and the debate that ensued between the competitive, promotional and cost based approaches. Three major questions are addressed: What factors and historical circumstances favoured the emergence of more or less efficient pricing schemes? Why did some enterprises opt for promotional rates while others defended the cost based alternative? What is the historical origin of marginal cost pricing? It is shown how the volatility of the costs that characterize hydro-electric production made this particular technology very sensitive to a cost approach towards pricing and to a seasonal and time-of-day perspective on rate systems.     

Housing flexibility problem: Review of recent limitations and solutions

The economic, technological, and cultural transformations of our present society influence various scales of our daily lives. In housing, these transformations include changes in the family nucleus and the activities performed in living spaces. Housing flexibility seeks to meet the multiple needs of users by changing their living spaces and functions. This study aims to explore housing flexibility through a review of relevant literature, discussion of valuable findings, and presentation of a contemporary panorama of the theme. Notions of flexibility are integrated to reinterpret the contemporary sense of dwelling. However, the lack of a well-defined concept of flexibility hinders the integration of methods and theories on the subject.     

A sensitivity analysis of a cost optimality study on the energy retrofit of a single-family reference building in Portugal

Improvement of the energy efficiency of residential buildings must ensure compliance with cost optimality criteria, assuming a specific lifespan of the building. At the same time, the energy retrofit of buildings ought to preserve their intrinsic architectural and heritage value. Portuguese residential buildings constructed before 1960 did not follow any energy efficiency rules. They represent 29% of the housing stock in the country and there is a high potential for increasing their energy efficiency. However, it costs more to implement envelope energy efficiency measures through retrofitting works than to provide for them in new buildings. An evaluation based on cost optimality criteria should therefore be performed. This work evaluates the energy performance of a Portuguese reference building typical of the pre-1960 building stock for different thicknesses of thermal insulation retrofit solutions (roof, facade, and ground floor) and systems. The study describes a sensitivity analysis that took a range of climate data, intervention costs, energy prices, discount rates, and energy needs into account. An energy needs factor dealt with the occupants’ habits and the effective reduction of energy consumption compared with the estimated energy needs.