The Expression of Chemokines Is Downregulated in a Pre-Clinical Model of TTR V30M Amyloidosis

Inflammation is a hallmark of several neurodegenerative disorders including hereditary amyloidogenic transthyretin amyloidosis (ATTRv). ATTRv is an autosomal dominant neurodegenerative disorder with extracellular deposition of mutant transthyretin (TTR) aggregates and fibrils, particularly in nerves and ganglia of the peripheral nervous system. Nerve biopsies from ATTRv patients show increased cytokine production, but interestingly no immune inflammatory cellular infiltrate is observed around TTR aggregates. Here we show that as compared to Wild Type (WT) animals, the expression of several chemokines is highly downregulated in the peripheral nervous system of a mouse model of the disease. Interestingly, we found that stimulation of mouse Schwann cells (SCs) with WT TTR results in the secretion of several chemokines, a process that is mediated by toll-like receptor 4 (TLR4). In contrast, the secretion of all tested chemokines is compromised upon stimulation of SCs with mutant TTR (V30M), suggesting that V30M TTR fails to activate TLR4 signaling. Altogether, our data shed light into a previously unappreciated mechanism linking TTR activation of SCs and possibly underlying the lack of inflammatory response observed in the peripheral nervous system of ATTRv patients.The work was funded by the project Norte-01-0145-FEDER-000008 - Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). JM was supported by FCT with a PhD fellowship SFRH/BD/129345/2017. MS is funded by FCT through Estı́mulo Individual ao Emprego Cientı́fico

Heteroscedastic latent variable modelling with applications to multivariate statistical process control

We present an approach for conducting multivariate statistical process control (MSPC) in noisy environments, i.e., when the signal to noise ratio is low, and, furthermore, noise standard deviation (uncertainty) affecting each collected value can vary over time, and is assumingly known. This approach is based upon a latent variable model structure, HLV (standing for heteroscedastic latent variable model), that explicitly integrates information regarding data uncertainty. Moderate amounts of missing data can also be handled in a coherent and fully integrated way through HLV. Several examples show the added value achieved under noisy conditions by adopting such an approach and a case study illustrates its application to a real industrial context of pulp and paper product quality data analysis.http://www.sciencedirect.com/science/article/B6TFP-4GX1HVW-2/1/c5e6b0a181b2fb4ffd7803ff38c9dac

Multiscale statistical process control with multiresolution data

An approach is presented for conducting multiscale statistical process control that adequately integrates data at different resolutions (multiresolution data), called MR-MSSPC. Its general structure is based on Bakshi's MSSPC framework designed to handle data at a single resolution. Significant modifications were introduced in order to process multiresolution information. The main MR-MSSPC features are presented and illustrated through three examples. Issues related to real world implementations and with the interpretation of the multiscale covariance structure are addressed in a fourth example, where a CSTR system under feedback control is simulated. Our approach proved to be able to provide a clearer definition of the regions where significant events occur and a more sensitive response when the process is brought back to normal operation, when it is compared with previous approaches based on single resolution data. © 2006 American Institute of Chemical Engineers AIChE J, 200

Measurement of a superficial texture by applying the alpha parameter on the profile P, for measuring a manual transmission gear

The objective of this work is to demonstrate the P Profile application in the measurement of superficial texture of the cone seat of the synchronization ring gear of a Mechanical Transmission. It is known that this superficial texture is an essential factor for the good performance and durability of a Mechanical Transmission, since the variation of this texture is directly linked to the synchronization failure, premature wear of the synchronization ring coupling guides, gear and sleeve

High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used

Surviving in a second language: survival processing effect in memory of bilinguals

Human memory likely evolved to serve adaptive functions, that is, to help maximise our chances of survival and reproduction. One demonstration of such adaptiveness is the increased retention of information processed in survival contexts, the so-called Survival Processing Effect (SPE). This study examined this effect in a native (L1) and in a second language (L2). This comparison is relevant to explore if emotionality is involved in the SPE, as emotional activation seems to be larger in L1 than in L2. Following the original survival processing procedure, participants rated the relevance of information to the survival and moving scenarios and performed a recognition (Experiment 1) or a free recall (Experiment 2) task in L1 or L2. In both experiments, the SPE was replicated in L1 but not in L2. The absence of the effect when emotional activation is less likely suggests that emotionality might play a role in the survival processing effect; nevertheless, additional studies are needed to further investigate this hypothesis.info:eu-repo/semantics/acceptedVersio

Staphylococcus epidermidis biofilms undergo metabolic and matrix remodeling under nitrosative stress

Funding Information: This work was financially supported by Fundação para a Ciência e Tecnologia (FCT) Project – PTDC/BIA-MIC/31566/2017, R&D unit MOSTMICRO-ITQB (UIDB/04612/2020 and UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). AO has a fellowship UI/BD/153389/2022 from FCT. The NMR data were acquired from CERMAX, ITQB-NOVA, Oeiras, Portugal, with equipment funded by FCT, project AAC 01/SAICT/2016. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments Publisher Copyright: Copyright © 2023 Oliveira, Saraiva and Carvalho.Staphylococcus epidermidis is a commensal skin bacterium that forms host- and antibiotic-resistant biofilms that are a major cause of implant-associated infections. Most research has focused on studying the responses to host-imposed stresses on planktonic bacteria. In this work, we addressed the open question of how S. epidermidis thrives on toxic concentrations of nitric oxide (NO) produced by host innate immune cells during biofilm assembly. We analyzed alterations of gene expression, metabolism, and matrix structure of biofilms of two clinical isolates of S. epidermidis, namely, 1457 and RP62A, formed under NO stress conditions. In both strains, NO lowers the amount of biofilm mass and causes increased production of lactate and decreased acetate excretion from biofilm glucose metabolism. Transcriptional analysis revealed that NO induces icaA, which is directly involved in polysaccharide intercellular adhesion (PIA) production, and genes encoding proteins of the amino sugar pathway (glmM and glmU) that link glycolysis to PIA synthesis. However, the strains seem to have distinct regulatory mechanisms to boost lactate production, as NO causes a substantial upregulation of ldh gene in strain RP62A but not in strain 1457. The analysis of the matrix components of the staphylococcal biofilms, assessed by confocal laser scanning microscopy (CLSM), showed that NO stimulates PIA and protein production and interferes with biofilm structure in a strain-dependent manner, but independently of the Ldh level. Thus, NO resistance is attained by remodeling the staphylococcal matrix architecture and adaptation of main metabolic processes, likely providing in vivo fitness of S. epidermidis biofilms contacting NO-proficient macrophages.publishersversionpublishe

Using emoji in response to customer reservation requests and service reviews

The use of paralinguistic cues—including emoji—in computer-mediated communication has become prevalent in recent years. Brands and service providers have also been using these cues in their communication strategies. And yet, research examining how such emoji use influences customers’ perception and behavior is still scarce. In two experiments (combined ), we tested if using emoji to reply to a customer request (restaurant reservation, Study 1) or online review (hotel experience, Study 2) influenced perceptions of the brands. The emoji used by the brand was always congruent with the valence of the situation. Results from both studies revealed that the presence (vs. absence) of emoji influenced consumers’ perception of the brand/service at several levels. Specifically, the restaurant/hotel was perceived to have a more informal communication style, have a warmer service, and be more modern. In Study 1, we also observed that emoji use had a positive impact on competence perception and reservation intentions. Importantly, these effects of emoji use were not moderated by the valence of the situation. Taken together, our results showed that emoji can influence different perceptions about brands and services and determine how customers relate to brands.info:eu-repo/semantics/publishedVersio