Learning Credible Models

In many settings, it is important that a model be capable of providing reasons for its predictions (i.e., the model must be interpretable). However, the model's reasoning may not conform with well-established knowledge. In such cases, while interpretable, the model lacks \textit{credibility}. In this work, we formally define credibility in the linear setting and focus on techniques for learning models that are both accurate and credible. In particular, we propose a regularization penalty, expert yielded estimates (EYE), that incorporates expert knowledge about well-known relationships among covariates and the outcome of interest. We give both theoretical and empirical results comparing our proposed method to several other regularization techniques. Across a range of settings, experiments on both synthetic and real data show that models learned using the EYE penalty are significantly more credible than those learned using other penalties. Applied to a large-scale patient risk stratification task, our proposed technique results in a model whose top features overlap significantly with known clinical risk factors, while still achieving good predictive performance

A road map for defining Good Environmental Status in the deep-sea

The development of tools to assess the Good Environmental Status (GES) in the Deep Sea (DS) is one of the aspects that ATLAS WP3 is addressing. GES assessment in the DS is challenging due to 1) the lack of baseline data, 2) the remoteness of the DS ecosystems, and 3) the limitations of the sampling methods currently available. Throughout the duration of the project, ATLAS will develop a suitable approach to address GES in the DS. During the 2nd General Assembly, we will present a draft for a “road map” to address GES in the DS as well some of the aspects discussed during the 2017 ICES WG on Deep Sea Ecosystems. The temporal and spatial scale at which GES should be assessed in the deep-sea is an important aspect to be considered. Due to the data limited situation and challenges posed to monitoring, it may well be the case that GES will have to be assessed at large spatial and temporal scales when comparing the shallower waters of the European Seas. For similar reasons, the type of indicators to be used may have to be simplified and likely be based on high-level analyses related to traits, pressures/risks, and habitat /ecosystem resilience. Ultimately, the results of the combined analyses of GES descriptors might bring to a potential refining or redefinition of the GES concept for the deep-sea

A Hexanuclear Mixed-Valence Oxovanadium(IV,V) Complex as a Highly Efficient Alkane Oxidation Catalyst

The new hexanuclear mixed-valence vanadium complex [V3O3(OEt)(ashz)(2)(mu-OEt)](2) (1) with an N,O-donor ligand is reported. It acts as a highly efficient catalyst toward alkane oxidations by aqueous H2O2. Remarkably, high turnover numbers up to 25000 with product yields of up to 27% (based on alkane) stand for one of the most active systems for such reactions

Nanomedicine for the delivery of RNA in cancer

The complexity, and the diversity of the different types of cancers allied to the tendency to form metastasis make treatment efficiency so tricky and often impossible due to the advanced stage of the disease in the diagnosis. In recent years, due to tremendous scientific breakthroughs, we have witnessed exponential growth in the elucidation of mechanisms that underlie carcinogenesis and metastasis. The development of more selective therapies made it possible to improve cancer treatment. Although interdisciplinary research leads to encouraging results, scientists still have a long exploration journey. RNA technology represents a promise as a therapeutic intervention for targeted gene silencing in cancer, and there are already some RNA-based formulations in clinical trials. However, the use of RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Thus, the use of nanomedicine employing nanoparticles to encapsulate RNA may represent a suitable platform to address the major challenges hampering its therapeutic application. In this review, we have revisited the potential of RNA and RNA-associated therapies to fight cancer, also providing, as support, a general overview of nanoplatforms for RNA delivery.This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through project UIDB/50006/2020

Evaluation of parasite and host phenolic composition and bioactivities − The practical case of Cytinus hypocistis (L.) L. and Halimium lasianthum (Lam.) Greuter

Cytinus hypocistis (L.) L. is a comestible holoparasite with great potential for cosmeceutical application. Although its high tannin content has been associated with its bioactive and inhibitory enzyme properties, this is the first report establishing a relationship between parasite and host (Halimium lasianthum (Lam.) Greuter) phenolic profile and bioactive properties. Thus, five extracts (aerial and root extracts of non-parasited and parasited H. lasianthum and C. hypocistis) were evaluated. The tentative identification of both species comprises 39 phenolic compounds. Hydrolysable tannins and flavonoids were the main identified groups in C. hypocistis and H. lasianthum extracts, respectively. Regarding bioactivities, C. hypocistis exhibited excellent antioxidant results both in Oxidative Haemolysis (OxHLIA) and inhibition of Thiobarbituric Acid Reactive Substances Formation (TBARS). The tested extracts presented antimicrobial inhibition, anti-inflammatory activity, and effective cytotoxicity against tumour cells. C. hypocistis exhibited the lowest cytotoxicity on a non-tumour cell line. Principal Component Analysis (PCA) was a suitable approach to analyse differences among samples, explaining up to 67% of data variability and suggesting no similarities between parasite and host phenolic composition and bioactivities. Therefore, this comparative study emphasises the significance of both species as a source of biologically active compounds.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). A. R. Silva is grateful to FCT and FSE for her Doctoral Grant (SFRH/BD/145834/2019). L. Barros, C. Pereira, I. Dias, and R. C. Calhelha are grateful to F.C.T. and P.I. for their contracts through the institutional scientific employment programme. The authors are also thankful to the FEDER-Interreg Espa˜na-Portugal programme for financial support through the project TRANSCoLAB: 0612_TRANS_CO_LAB_2_P and to ERDF through the Regional Operational Program North 2020, within the scope of the Project GreenHealth - Norte-01–0145-FEDER-000042. This research was also funded by the Serbian Ministry of Education, Science and Technological Development (Contract No. 451–03-9/2021–14/200007).info:eu-repo/semantics/publishedVersio

Indoor school environment: easy and low cost to assess inorganic pollutants

Total particulate matter (TPM) was passively collected inside two classrooms of each of five elementary schools in Lisbon, Portugal. TPM was collected in polycarbonate filters with a 47 mm diameter, placed inside of uncovered plastic petri dishes. The sampling period was from 19 May to 22 June 2009 (35 days exposure) and the collected TPM masses varied between 0.2 mg and 0.8 mg. The major elements were Ca, Fe, Na, K, and Zn at μg level, while others were at ng level. Pearson′s correlation coefficients above 0.75 (a high degree of correlation) were found between several elements. Soil-related, traffic soil re-suspension and anthropogenic emission sources could be identified. Blackboard chalk was also identified through Ca large presence. Some of the determined chemical elements are potential carcinogenic. Quality control of the results showed good agreement as confirmed by the application of u-score test

Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation

Funding: This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [Grant BB/M010996/1] via EASTBIO Doctoral Training Partnership studentships to B. J. R. and G. F., by Stiftelsen Olle Engkvist Byggmästare [Grant 190-0335] and the Knut and Alice Wallenberg Foundation [Grants 2018.0140 and 2019.0431] to S.C.L.K., and by the European Union’s Horizon 2020 Research and Innovation Programme via a Marie Sklodowska-Curie fellowship [Grant 890562] to M.C. The simulations were enabled by resources provided by the Swedish National Infrastructure for Supercomputing (SNIC, UPPMAX), partially funded by the Swedish Research Council [Grant 2016-07213].ATP phosphoribosyltransferase catalyses the first step of histidine biosynthesis and is controlled via a complex allosteric mechanism where the regulatory protein HisZ enhances catalysis by the catalytic protein HisGS while mediating allosteric inhibition by histidine. Activation by HisZ was proposed to position HisGS Arg56 to stabilise departure of the pyrophosphate leaving group. Here we report active-site mutants of HisGS with impaired reaction chemistry which can be allosterically restored by HisZ despite the HisZ:HisGS interface lying ~20 Å away from the active site. MD simulations indicate HisZ binding constrains the dynamics of HisGS to favour a preorganised active site where both Arg56 and Arg32 are poised to stabilise leaving-group departure in WT-HisGS. In the Arg56Ala-HisGS mutant, HisZ modulates Arg32 dynamics so that it can partially compensate for the absence of Arg56. These results illustrate how remote protein-protein interactions translate into catalytic resilience by restoring damaged electrostatic preorganisation at the active site.Publisher PDFPeer reviewe

Plant extracts as potential bioactive food additives

Plant extracts have been proposed as antimicrobial agents and health-promoters to be included in a variety of food products. In this sense, this work aimed to evaluate the bioactivities of infusions, decoctions and hydroethanolic extracts of six aromatic plants, namely, basil, lemon balm, lavender, sage, spearmint, and tarragon. The novelty of this study is related to the recent trend to replace chemical additives with more natural, plant-based ones, to meet consumers’ demands. The results highlighted the antimicrobial, antioxidant, and anti-inflammatory effects of several of these extracts, thus emphasising their capability to prevent food spoilage and promote health benefits. In this sense, our research revealed the potential of some plant extracts as potential food additives.The authors are grateful to the EU PRIMA program and the Portuguese Foundation for Science and Technology (FCT) for funding the ArtiSaneFood project (PRIMA/0001/2018) and for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). This study was supported by FCT under the scope of the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte. This work has been supported by the Ministry of Education, Science and Technological Development of Republic of Serbia (451-03-68/2020-14/200007).B.N.S. wishes to acknowledge the financial support provided by FCT through the Ph.D. grant SFRH/BD/137801/2018. R.C.C., L.B., U.G.-B. and J.P. (CEECIND/01011/2018) acknowledge the national funding by FCT, P.I., through the Institutional Scientific Employment Program contract. The project Healthy-PETFOOD is acknowledged, for the contract of C. Caleja (Healthy-PETFOOD (POCI-01-0247-FEDER-047073)), as well as the Project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®, for the contract of E. Pereira.info:eu-repo/semantics/publishedVersio