Machine learning systems are becoming increasingly ubiquitous. These systems’s adoption has been expanding, accelerating the shift towards a more algorithmic society, meaning that algorithmically ...informed decisions have greater potential for significant social impact. However, most of these accurate decision support systems remain complex black boxes, meaning their internal logic and inner workings are hidden to the user and even experts cannot fully understand the rationale behind their predictions. Moreover, new regulations and highly regulated domains have made the audit and verifiability of decisions mandatory, increasing the demand for the ability to question, understand, and trust machine learning systems, for which interpretability is indispensable. The research community has recognized this interpretability problem and focused on developing both interpretable models and explanation methods over the past few years. However, the emergence of these methods shows there is no consensus on how to assess the explanation quality. Which are the most suitable metrics to assess the quality of an explanation? The aim of this article is to provide a review of the current state of the research field on machine learning interpretability while focusing on the societal impact and on the developed methods and metrics. Furthermore, a complete literature review is presented in order to identify future directions of work on this field.
A highly enantioselective copper‐catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos, a newly developed imidazole‐based chiral biaryl P,N ligand, and copper ...bromide to effect a three‐component reaction between a quinoline, a terminal alkyne, and ethyl chloroformate. Under the reaction conditions, the desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates a wide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons. Efficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+)‐galipinine, (+)‐angustureine, and (−)‐cuspareine are reported.
Stacking the deck: Using the axially chiral imidazole‐based biaryl, StackPhos, a highly enantioselective copper‐catalyzed alkynylation of quinolines has been developed. The method tolerates an unprecedented alkyne scope and both electron‐rich and electron‐deficient quinolines. Efficient syntheses of the tetrahydroquinoline alkaloids (+)‐galipinine, (+)‐angustureine, and (−)‐cuspareine are reported. DIPEA=diisopropylethylamine.
Abstract NLRP3 inflammasome activation seems to be a culprit behind the chronic inflammation characteristic of obesity and insulin resistance (IR). Nutrient excess generates danger-associated ...molecules that activate NLRP3 inflammasome-caspase 1, leading to maturation of IL-1β and IL-18, which are proinflammatory cytokines released by immune cells infiltrating the adipose tissue (AT) from obese subjects. Although several studies have reported an association of the NLRP3 inflammasome with obesity and/or IR; contradictory results were also reported by other studies. Therefore, we conducted a systematic review to summarize results of studies that evaluated the association of the NLRP3 with obesity and IR. Nineteen studies were included in the review. These studies focused on NLRP3 expression/polymorphism analyses in AT. Overall, human studies indicate that obesity and IR are associated with increased NLRP3 expression in AT. Studies in obese mice corroborate this association. Moreover, high fat diet (HFD) increases Nlrp3 expression in murine AT while calorie-restricted diet decreases its expression. Hence, Nlrp3 blockade in mice protects against HFD-induced obesity and IR. NLRP3 rs10754558 polymorphism is associated with risk for T2DM in Chinese Han populations. In conclusion, available studies strongly points for an association between NLRP3 inflammasome and obesity/IR.
Future changes in the mean, maximum, and minimum surface temperature over Europe are investigated according to CMIP6 future climate projections. All the temperature variables are projected to ...increase across Europe particularly in northern and southernmost latitudes, where according to SSP5-8.5 the warming can reach 2–3 (5–6) °C at the middle (end) of the current century. The warming is particularly strong in Northern (Mediterranean) areas in winter (summer) seasons. The occurrence of hot days (mean temperature > 30 °C) is projected to increase in all southern Europe by the end of the century (> 40–60 days/year), particularly in the southern parts of the Iberian Peninsula and Turkey. Increases in the occurrence of very hot days (maximum temperature > 40 °C) are projected in the central-southern areas of the Iberian Peninsula (30–40 days/year) and southern Turkey (> 50 days/year) in the end of the century. Tropical nights are expected to increase throughout the century in all Europe (except the northernmost latitudes), particularly at southern Europe for the 2081–2100 period (50–80 nights/year). Frost days (minimum temperature < 0 °C) are expected to occur less in all Europe towards the end of the century, with less than 50–70 days/year in central Europe and even less in Scandinavia and north-eastern Russia.
Electrocardiogram signals acquired through a steering wheel could be the key to seamless, highly comfortable, and continuous human recognition in driving settings. This paper focuses on the ...enhancement of the unprecedented lesser quality of such signals, through the combination of Savitzky-Golay and moving average filters, followed by outlier detection and removal based on normalised cross-correlation and clustering, which was able to render ensemble heartbeats of significantly higher quality. Discrete Cosine Transform (DCT) and Haar transform features were extracted and fed to decision methods based on Support Vector Machines (SVM), k-Nearest Neighbours (kNN), Multilayer Perceptrons (MLP), and Gaussian Mixture Models - Universal Background Models (GMM-UBM) classifiers, for both identification and authentication tasks. Additional techniques of user-tuned authentication and past score weighting were also studied. The method's performance was comparable to some of the best recent state-of-the-art methods (94.9% identification rate (IDR) and 2.66% authentication equal error rate (EER)), despite lesser results with scarce train data (70.9% IDR and 11.8% EER). It was concluded that the method was suitable for biometric recognition with driving electrocardiogram signals, and could, with future developments, be used on a continuous system in seamless and highly noisy settings.
Multidrug resistance (MDR) in cancer is one of the main limitations for chemotherapy success. Numerous mechanisms are behind the MDR phenomenon wherein the overexpression of the ATP-binding cassette ...(ABC) transporter proteins P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein 1 (MRP1) is highlighted as a prime factor. Natural product-derived compounds are being addressed as promising ABC transporter modulators to tackle MDR. Flavonoids and terpenoids have been extensively explored in this field as mono or dual modulators of these efflux pumps. Nitrogen-bearing moieties on these scaffolds were proved to influence the modulation of ABC transporters efflux function. This review highlights the potential of semisynthetic nitrogen-containing flavonoid and terpenoid derivatives as candidates for the design of effective MDR reversers. A brief introduction concerning the major role of efflux pumps in multidrug resistance, the potential of natural product-derived compounds in MDR reversal, namely natural flavonoid and terpenoids, and the effect of the introduction of nitrogen-containing groups are provided. The main modifications that have been performed during last few years to generate flavonoid and terpenoid derivatives, bearing nitrogen moieties, such as aliphatic, aromatic and heterocycle amine, amide, and related functional groups, as well as their P-gp, MRP1 and BCRP inhibitory activities are reviewed and discussed.
Dear Editor, Almost all reports on liver injury in patients with 2019 coronavirus disease (COVID-19) found blood liver tests to be frequently abnormal, especially in patients with more severe ...disease, but with substantial heterogeneity 1. ...blood liver tests’ abnormalities were frequently thought to be of doubtful clinical value. Most studies have described blood liver tests in a single time point, usually at inclusion 2, 3. ...we used our case series of the first 20 consecutive patients with COVID-19 admitted to the intensive care unit (ICU) at Curry Cabral Hospital in Lisbon, Portugal, from March 10, 2020, onwards, to describe the temporal evolution of blood liver tests. Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression.
Robust electrocatalysts toward the resourceful and sustainable generation of hydrogen by splitting of water via electrocatalytic hydrogen evolution reaction (HER) are a prerequisite to realize ...high-efficiency energy research. Highly electroactive catalysts for hydrogen production with ultralow loading of platinum (Pt) have been under exhaustive exploration to make them cutting-edge and cost-effectively reasonable for water splitting. Herein, we report the synthesis of hierarchically structured nickel pyrophosphate (β-Ni2P2O7) by a precipitation method and nickel phosphate (Ni3(PO4)2) by two different synthetic routes, namely, simple cost-effective precipitation and solution combustion processes. Thereafter, Pt-decorated nickel pyrophosphate and nickel phosphate (β-Ni2P2O7/Pt and Ni3(PO4)2/Pt) were prepared by using potassium hexachloroplatinate and ascorbic acid. The fabricated novel nickel pyrophosphate and nickel phosphate/Pt materials were utilized as potential and affordable electrocatalysts for HER by water splitting. The detailed electrochemical studies revealed that the β-Ni2P2O7/Pt (1 μg·cm–2 Pt) electrocatalyst showed excellent electrocatalytic performances for HER in acidic solution with an overpotential of 28 mV at −10 mA·cm–2, a Tafel slope of 32 mV·dec, and an exchange current density (j 0) of −1.31 mA·cm–2, which were close to the values obtained using the Vulcan/Pt (8.0 μg·cm–2 Pt), commercial benchmarking electrocatalyst with eight times higher Pt amount. Furthermore, the β-Ni2P2O7/Pt electrocatalyst maintains an excellent stability for over −0.1 V versus RHE for 12 days, keeping j 0 equal after the stability test (−1.28 mA cm–2). Very well-distributed Pt NPs inside the “cages” on the β-Ni2P2O7 structure with a crystalline pattern of 0.67 nm distance to the Ni2P2O7/Pt electrocatalyst, helping the Volmer–Tafel mechanism with the Tafel reaction as a major rate-limiting step, help to liberate very fast the Pt sites after HER. The high electrocatalytic performance and remarkable durability showed the β-Ni2P2O7/Pt material to be a promising cost-effective electrocatalyst for hydrogen production.
The TDE focus group seeks to understand how disequilibria are generated in geological, chemical and biological systems, and how these disequilibria can lead to emergent phenomena, such as ...self-organization in bounded conditions eventuating in metabolism. Some planetary water-rock interfaces generate electrochemical disequilibria (e.g. electron, proton and/or ion gradients), and life itself is an out-of-equilibrium system that operates by harnessing such gradients across membranes. Disequilibrium in inorganic chemical systems also leads to the formation of a variety of patterns, structures, and dynamical systems. Understanding geochemical far-from-equilibrium systems and bounded self-organizing processes may be instructive in revealing some of the processes behind lifes origin. In this workshop paper we will detail the outcomes of the 8th TDE meeting in Tokyo, summarizing the focus groups discussions regarding 1) the determination of some of the required conditions for generating geochemical disequilibria for life to originate on a wet, rocky world; 2) the spatial and temporal scales for the origin of life;3) lifes use of disequilibria and the relationship of life itself to self-organizing systems in an aqueous inorganic milieu; and 4) pathways forward for achieving the laboratory simulation of far-from-equilibrium systems concerning prebiotic chemical processes.
Many hypotheses have been postulated to define the etiology of sporadic Parkinson's and Alzheimer's disorders (PD and AD) but there is no consensus on what causes these devastating age-related ...diseases. Braak staging of both pathologies helped researchers to better understand the progression and to identify their prodromal and symptomatic phases. Indeed, it is well accepted that Lewy body pathology and neurofibrillary tangles appearance correlates with disease progression and severity of symptoms in PD and AD, respectively. Additionally, several studies in PD and AD models try to disclose which cellular mechanisms are defaulted and trigger the neurodegenerative process that culminates with neuronal death causing PD and AD classical symptomatology. Herein, we determined expression levels of proteins involved in microtubule assembly, autophagic-lysosomal pathway and unfolded protein response in the cortex, hippocampus and SNpc of PD and AD patients, vascular dementia patients and aged-match controls. The differential expression allowed us to determine which pathways are determinant to synaptic dysfunction and to establish a time line for disease progression. Our results allow us to challenge the hypothesis that both PD and AD pathologies are caused by α-synuclein or Aβ pathology propagation throughout the brain in a prion-like manner.
PDF
