Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Nonsense-Mediated RNA Decay by the Tumor Microenvironment Promotes Tumorigenesis

ABSTRACT While nonsense-mediated RNA decay (NMD) is an established mechanism to rapidly degrade select transcripts, the physiological regulation and biological significance of NMD are not well characterized. We previously demonstrated that NMD is inhibited in hypoxic cells. Here we show that the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) translation initiation factor by a variety of cellular stresses leads to the inhibition of NMD and that eIF2α phosphorylation and NMD inhibition occur in tumors. To explore the significance of this NMD regulation, we used an unbiased approach to identify approximately 750 NMD-targeted mRNAs and found that these mRNAs are overrepresented in stress response and tumor-promoting pathways. Consistent with these findings, the inhibition of NMD promotes cellular resistance to endoplasmic reticulum stress and encourages tumor formation. The transcriptional and translational regulations of gene expression by the microenvironment are established mechanisms by which tumor cells adapt to stress. These data indicate that NMD inhibition by the tumor microenvironment is also an important mechanism to dynamically regulate genes critical for the response to cellular stress and tumorigenesis.
Linkage Quality Analysis of GeoNames in the Semantic Web

We examine the GeoNames gazetteer as a hub of Linked Geospatial Data. We survey quality and linkage characteristics to understand how well it supports the traversal of the Semantic Web and which limitations exist. We examine different traversal scenarios originating with GeoNames and present findings related to link availability and distribution along language and geospatial dimensions and discuss the role of cross-lingual issues.
Antenna Diversity Schemes for Uplink Frequency-Domain Multiuser Detection in CP-Assisted DS-CDMA Systems

In this paper, Antenna Diversity (AD) schemes are presented for Frequency-Domain (FD) Multi-User Detection (MUD) in the Up-Link (UL) of cellular systems which apply CP (Cyclic Prefix) assisted DS-CDMA (Direct Sequence Code Division Multiple Access). Alamouti-based Space-Time-Code (STC) was applied to exploit transmitter (TX) diversity. The MUD and the diversity combining in the receiver (RX) are MMSE (Minimum Mean Square Error) based. Simulation results show that with moderate computational complexity, the SIMO and MIMO schemes have achieved better performance than the Iterative Block Decision Feedback Equalization (IB-DFE) based scheme in [1]. It was also shown that SIMO is superior to MISO in terms of diversity exploitation and achieves the best tradeoff between complexity and performance.
The Use of Regularized Least Squares Minimization for the Deconvolution of SEM Images

Major advances are currently taking place in image processing algorithm development. When combined with today’s high speed computers utilizing multicore processing and very large memories the door is opened to the practical application of regularization techniques to the restoration of SEM images with improved spatial resolution. It is well recognized that an observed SEM image can be thought of as the convolution of a point spread function (psf) arising from measurement broadening and the true structure imaged. However, even with the abovementioned advances, a variety of additional limitations arise that are preventing the practical implementation of deconvolution to SEM image restoration. These factors include noise as well as a lack of detailed knowledge of the psf since no experimental technique is currently available to directly measure it with level of spatial resolution required. Furthermore, the problem is complicated by other factors such as specimen drift, contamination, the three dimensionality of specimen, signal excitation volume considerations, non-linearity in the scanning system and also nonlinear behavior in the detection chain [1].
Advances in the Physiology of GPR55 in the Central Nervous System

Background: The G protein-coupled receptor 55 (GPR55) is a mammalian orphan receptor that awaits a formal classification. There are an increasing number of reports directed to know the physiology and pathophysiology of this receptor. Lamentably, its functions in the central nervous system (CNS) have been scarcely elucidated. Methods: A bibliographic search in PubMed database about GPR55 actions in the CNS was made. The information was grouped for brain structures to facilitate the interpretation. Finally, we constructed a schematic representation of the current knowledge about the potential participation of GPR55 in some physiological and pathophysiological events. Results: Seventy nine papers were included in the review. Only few of them showed data about GPR55 (mRNA/protein) expression in multiple brain areas. The rest showed findings in different preparations both in vitro and in vivo conditions that allowed us to speculate a potential activity of GPR55 in the different brain areas. Conclusion: GPR55 mRNA is expressed in several brain areas as the hippocampus, hypothalamus, frontal cortex and cerebellum; but due to the lack of information, only some speculative information about its function in these regions has been suggested. Therefore, this review provide relevant information to motivate further research about GPR55 physiology/pathophysiology in the CNS.
Recent advances on conversion and co-production of acetone-butanol-ethanol into high value-added bioproducts

Abstract Butanol is an important bulk chemical and has been regarded as an advanced biofuel. Large-scale production of butanol has been applied for more than 100 years, but its production through acetone–butanol–ethanol (ABE) fermentation process by solventogenic Clostridium species is still not economically viable due to the low butanol titer and yield caused by the toxicity of butanol and a by-product, such as acetone. Renewed interest in biobutanol as a biofuel has spurred technological advances to strain modification and fermentation process design. Especially, with the development of interdisciplinary processes, the sole product or even the mixture of ABE produced through ABE fermentation process can be further used as platform chemicals for high value added product production through enzymatic or chemical catalysis. This review aims to comprehensively summarize the most recent advances on the conversion of acetone, butanol and ABE mixture into various products, such as isopropanol, butyl-butyrate and higher-molecular mass alkanes. Additionally, co-production of other value added products with ABE was also discussed.
HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives

HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies.
Fibrin clot structure - pro-fibrinolytic effect of oral contraceptives in apparently healthy women

Summary Fibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism. The study included 70 women treated with seven different OC-formulations. Blood was collected at baseline and after six months of OCs. The plasma concentration of fibrinogen, thrombin-antithrombin complex (TAT), plasminogen, plasmin-antiplasmin complex (PAP), D-Dimer and thrombin generation measures were determined. Fibrin structure measures and fibrin clot lysis not affected by the plasma concentration of plasminogen activators and inhibitors were determined. OCs increased the concentration of fibrinogen, TAT, plasminogen, PAP and D-dimer significantly and affected measures of thrombin generation (p<0.001). The maximal optical density of fibrin (p<0.001), the fibrin fibre density (p=0.03), fibrin fibre diameter (p=0.003), fibrin mass-length ratio (p<0.001) and lysis per hour (p<0.001) increased significantly upon OC-treatment. Lysis per hour was not correlated to the concentration of plasminogen. We conclude that the effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC. These alterations may counterbalance the OC-induced increased thrombin generation and reduced coagulation inhibitory potential, contributing to maintenance of the haemostatic balance in women receiving OCs.
Influence of yttrium addition on the corrosion behaviour of as-cast Mg–8Li–3Al–2Zn alloy

The influence of yttrium on the microstructure and corrosion behaviour of as-cast Mg–8Li–3Al–2Zn–xY alloys was investigated. The results show that Y addition leads to the formation of Al2Y particles and the transformation of α-Mg from the long needle-like to the round-like. The noble Al2Y particles on the grain boundary inhibit the galvanic corrosion between β-Li phase and α-Mg phase, and also weaken the corrosion occurrence inside β-Li phase due to the decrease of the AlLi phase. With Y addition, the corrosion resistance is improved gradually, especially when the content of Y is up to 1.5 wt-%. Moreover, Y addition makes the corrosion film become more compact, which can prevent the base materials from being attacked continuously.
Genèse des contraintes résiduelles de nitruration. Étude expérimentale et modélisation

Nitriding of steel parts leads to an increase in their service lifetime as a result of the improvement in the fatigue strength of the material due to surface hardening in combination with the generation of residual compressive stresses in the near-surface layers. A new method for calculating the local changes in volume is proposed.This method is based on a thermodynamical evaluation of the volume fractions of the various types of precipitates existing at equilibrium in the nitrided layer. A theoretical approach using micromechanical concepts has put into evidence that the residual stress fields built up in each phase are essentially different and hence different from the average stress field. Experimental checking has been performed using the X-ray diffraction technique to establish the residual stress depth profiles in the ferrite phase and the hole-drilling method to determine the mean residual stress field as a function of depth in the nitrided layer. The analysis of the diffraction peak profiles has shown that the residual plastic strains are negligible in nitrided layers. The integral breadth of the diffraction peaks is almost exclusively indicative of the number-average crystallite size in the ferrite phase. In addition, direct observations in the TEM have confirmed that plastic deformation is localized in the vicinity of the precipitates. Residual stress relaxation has been investigated as a function of time and temperature. It appeared clearly that the relaxation phenomena are closely related to the diffusion of nitrogen during the process and that the residual fields generated nitriding show a high degree of thermal stability. Application of the proposed method to the prediction of the mechanical behaviour of a thin plate nitrided on one side confirms the previous results. Such a specimen could be used as a means of evaluating the intensity of a particular nitriding operation in common industrial practice (patent pending)
ADAMTS13 deficiency promotes microthrombosis in a murine model of diet-induced liver steatosis

Summary ADAMTS13 cleaves ultralarge multimeric von Willebrand Factor (VWF), thereby preventing formation of platelet-rich microthrombi. ADAMTS13 is mainly produced by hepatic stellate cells, and numerous studies have suggested a functional role of ADAMTS13 in the pathogenesis of liver diseases. The aim of our study was to investigate a potential role of ADAMTS13 in formation of hepatic microthrombi and development of non-alcoholic steatohepatitis (NASH), and furthermore to evaluate whether plasmin can compensate for the absence of ADAMTS13 in removal of thrombi. Therefore, we used a model of high-fat diet-induced steatosis in Adamts13 deficient (Adamts13−/−) and wild-type (WT) control mice. Microthrombi were more abundant in the liver of obese Adamts13−/− as compared to obese WT or to lean Adamts13−/− mice. Obese Adamts13−/− mice displayed lower platelet counts and higher prevalence of ultra-large VWF multimers. Hepatic plasmin-α2-antiplasmin complex levels were comparable for obese WT and Adamts13−/− mice and were lower for lean Adamts13−/− than WT mice, not supporting marked activation of the fibrinolytic system. High fat diet feeding, as compared to normal chow, resulted in enhanced liver triglyceride levels for both genotypes (p < 0.0001) and steatosis (p < 0.0001 for WT mice, p = 0.002 for Adamts13−/− mice) without differences between the genotypes. Expression of markers of inflammation, oxidative stress, steatosis and fibrosis was affected by diet, but not by genotype. Thus, our data confirm that obesity promotes NASH, but do not support a detrimental role of ADAMTS13 in its development. However, Adamts13 deficiency in obese mice promotes hepatic microthrombosis, whereas a compensatory role of plasmin in removal of microthrombi in the absence of ADAMTS13 could not be demonstrated.
Model Predictive Control of Power Converters for Robust and Fast Operation of AC Microgrids

This paper proposes the application of a finite control set model predictive control (FCS-MPC) strategy in standalone ac microgrids (MGs). AC MGs are usually built from two or more voltage source converters (VSCs) which have the capability of regulating the voltage at the point of common coupling, while sharing the load power at the same time. Those functionalities are conventionally achieved by hierarchical linear control loops. However, they present severe limitations in terms of slow transient response and high sensitivity to parameter variations. This paper aims to mitigate these problems by first introducing an improvement of the FCS-MPC strategy for a single VSC that is based on explicit tracking of derivative of the voltage reference trajectory. Using only a single step prediction horizon, the proposed strategy exhibits very low computational expense, but provides steady-state performance comparable to carrier-based sinusoidal PWM, while its transient response and robustness to parameter variation is far superior to hierarchical linear control. These benefits are exploited in a general ac MG setting where a methodology for paralleling multiple FCS-MPC regulated VSCs is described. Such an MG is characterized by rapid transient response, inherent stability in all operating conditions, and fully decentralized operation of individual VSCs. These findings have been validated through comprehensive simulation and experimental verification.
High-Temperature Resistance in Alkali-Activated Cement

This paper discusses the results of tests conducted to ascertain at high temperatures the mechanical behavior of cements whose most prominent characteristic is the absence or near absence of Portland cement in their composition. More specifically, it reports on the study of three binders: (a) Portland cement (control); (b) 100% sodium silicate-activated fly ash; and (c) a blend of 70% ash+30% clinker activated with solid-state activators (solid sodium silicate+Na2CO3). Two types of tests were conducted: (i) tests to determine the mechanical strength and fracture toughness of the three materials between 25° and 600°C and (ii) postthermal treatment tests to evaluate the residual strength after 1 h of exposure to temperatures ranging from 200° to 1000°C. XRD and SEM techniques were also deployed to track the mineralogical and microstructural variations in the materials as a result of such an exposure. The findings showed that a pseudo-viscous phase is generated in alkaline cements at around 600°C that would explain the decline in strength observed when specimens were loaded at increasing temperatures. This phase and its subsequent recrystallization into new phases (nepheline, albite, and gehlenite) were also responsible for the high-residual mechanical strength values observed in these materials after exposure to high temperatures and subsequent cooling but absent in OPC.
Voltage Sensor Movements

The voltage dependence of K+, Na+, and Ca2+ channels is brought about by a voltage sensor that moves ∼12–13 e0 across the entire electric field (Schoppa et al., 1992; Hirschberg et al., 1996; Noceti et al., 1996). In the case of Shaker K+ channel it is known which residues are responsible for this large amount of gating charge. This was found by measuring the total gating charge movement per channel after each of the putative charged residues (basic or acidic) were neutralized one by one (Aggarwal and MacKinnon, 1996; Seoh et al., 1996). These studies revealed that the four most extracellularly located basic residues of the S4 segment (R362, R365, R368, and R371) and the most intracellular acidic residue in the S2 segment (E293) are the major contributors to the gating charge movement. The simple assumption that all these residues move across the entire electric field accounts for more than the measured total gating charge. This means that the movement of at least some of the charged residues is only partial within the electric field.
Association Between Asymmetry in Knee Extension Strength and Balance in a Community-Dwelling Elderly Population: A Cross-Sectional Analysis

Objective To evaluate the association between balance function and asymmetry of knee extension strength in an elderly Korean population. Methods The strength of the knee extensors in each leg was measured in 306 community-dwelling elderly subjects (age, 76.70±4.85 years) and 25 young healthy subjects (age, 34.23±8.93 years). Based on the difference in strength of both legs, the elderly subjects were divided into symmetric (n=128) and asymmetric (n=178) strength groups using an asymmetry cutoff 20%. We determined the postural control ability of the subjects using InBody posturography, Berg Balance Scale (BBS), Timed Up and Go test (TUG) and Short Physical Performance Battery (SPPB). The sway index (SI) of the subjects in four positions was assessed using posturography. Results The group with asymmetric strength presented a significantly higher SI than the group with symmetric strength, in the normal position with eyes open and eyes open on pillows. In the normal position with the eyes closed and in postures with the eyes closed on pillows, the statistical analysis revealed no significant differences between the two groups. The three tests for physical performance (BBS, TUG, and SPPB) show no statistically significant difference between the two groups. Conclusion The asymmetric strength group showed a significantly lower balance than the group with symmetric strength based on several posturographic parameters. Ambulatory elderly individuals with asymmetry in knee extension strength, showed deficits in balance control even in normal clinical tests.
Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori‐infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose‐6‐phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro‐survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The potential and challenges of alternative sources of β cells for the cure of type 1 diabetes

The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure. New and infinite sources of β cells are strongly required. In this review, we make an overview of the most promising and advanced β cell production strategies. Particular hope is placed in pluripotent stem cells (PSC), both embryonic (ESC) and induced pluripotent stem cells (iPSC). The first phase 1/2 clinical trials with ESC-derived pancreatic progenitor cells are ongoing in the United States and Canada, but a successful strategy for the use of PSC in patients with diabetes has still to overcome several important hurdles. Another promising strategy of generation of new β cells is the transdifferentiation of adult cells, both intra-pancreatic, such as alpha, exocrine and ductal cells or extra-pancreatic, in particular liver cells. Finally, new advances in gene editing technologies have given impetus to research on the production of human organs in chimeric animals and on in situ reprogramming of adult cells through in vivo target gene activation.