A biased random‐key genetic algorithm for OSPF and DEFT routing to minimize network congestion

Interior gateway routing protocols like Open Shortest Path First (OSPF) and Distributed Exponentially Weighted Flow Splitting (DEFT) send flow through forward links toward the destination node. OSPF routes only on shortest‐weight paths, whereas DEFT sends flow on all forward links, but with an exponential penalty on longer paths. Finding suitable weights for these protocols is known as the weight setting problem (WSP). In this paper, we present a biased random‐key genetic algorithm for WSP using both protocols. The algorithm uses dynamic flow and dynamic shortest path computations. We report computational experiments that show that DEFT achieves less network congestion when compared with OSPF, while, however, yielding larger delays.     

Adaptive quasi-interpolating quartic splines

We present an adaptive quasi-interpolating quartic spline construction for regularly sampled surface data. The method is based on a uniform quasi-interpolating scheme, employing quartic triangular patches with C ¹-continuity and optimal approximation order within this class. Our contribution is the adaption of this scheme to surfaces of varying geometric complexity, where the tiling resolution can be locally defined, for example driven by approximation errors. This way, the construction of high-quality spline surfaces is enhanced by the flexibility of adaptive pseudo-regular triangle meshes. Numerical examples illustrate the use of this method for adaptive terrain modeling, where uniform schemes produce huge numbers of patches.     

Locally perceiving hard global constraints in multi-agent scheduling

We propose how to model enterprise facilities (like factories, warehouses, etc.) in a multi-product production/distribution network, capacity management at those facilities, and scheduling agents which act as enterprise managers, taking decisions that affect the available capacity. A coordination mechanism through which scheduling agents can locally perceive hard global temporal constraints is also proposed.     

Impact assessment of odours emitted by a wastewater treatment plant

Complaints from the Domingos Martins population about sewage odours in the city made the district attorney order an impact assessment of the odours emitted by the city wastewater treatment plant (WWTP). This study comprised various techniques, models and population surveys. In 2007, an odour emission model proved that the main hydrogen sulphide emitter was the aeration tank of the WWTP (13.5 g h(-1)) and such emissions, according to CALPUFF model, should be perceived in the whole Domingos Martins city centre area. In this area, 58% of those interviewed were annoyed by the WWTP odours. However, in 2009, the odour monitoring panel recorded few odour occurrences. A second population survey showed that hereafter only 20% of those interviewed were annoyed by the WWTP emissions. Odour emission and dispersion models run with 2010 data proved a drastic reduction of the WWTP aeration tank emissions and consequently the city centre was not bothered by WWTP emissions anymore. The odour emission reduction was due to the modification of the WWTP aeration tank system. Despite the odour emission reduction, houses located southeast of the WWTP were still annoyed by sewage odours. However, in this part of the town, other sources of sewage odours have been found.     

Volatilization of hydrogen sulfide from a quiescent surface

Air-water mass transfer of hydrogen sulfide from a shallow tank with a quiescent surface under the influence of weak wind stress on the water surface was studied numerically using a two-dimensional model. The flow field in the tank was investigated using a computational code based on a finite volume, which is used to numerically solve momentum, mass and continuity conservation equations. The results show that water phase flow field is strongly dependent on the wind-induced surface velocity and the aspect ratio of the tank. Based on the numerical study, the liquid-side mass transfer coefficient is correlated with Reynolds number (R(e)), tank aspect ratio (AR) and Schmidt number (S(c)). Overall mass transfer coefficient (K(L)) values extend further downstream as the R(e) number increases.     

Fine structure of the male accessory glands of Triatoma rubrofasciata (De Geer, 1773) (Hemiptera, Triatominae)

Male of Triatoma rubrofasciata has four elongated sac-like reproductive mesodermic accessory glands, lined by an inner single layer of secretory cells, with basal plasma membrane infolds and short apical microvilli, and externally enveloped by a thin visceral muscle layer. The secretory cells have a well-developed rough endoplasmic reticulum, Golgi complex, mitochondria, and secretory granules. In one day old adult the gland cells are poorly developed, presenting small, electron-transparent secretory granules scattered among the rough endoplasmatic reticulum, whereas in three days old adult these cells have the cisternae of the rough endoplasmatic reticulum varing size degree, filled with granular electrondense content. In five days old males the secretory granules increase in diameter, being released to the gland lumen. Therefore, there is an increase of the secretory activity according to male maturation.     

Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.     

The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.     

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.