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Phase separation is a ubiquitous process that compartmentalizes many cellular pathways. Given that the same interactions that drive phase separation mediate the formation of complexes below the saturation concentration, the contribution of condensates vs complexes to function is not always clear. Here, we characterized several new cancer-associated mutations of the tumor suppressor Speckle-type POZ protein (SPOP), a substrate recognition subunit of the Cullin3-RING ubiquitin ligase (CRL3), which pointed to a strategy for generating separation-of-function mutations. SPOP self-associates into linear oligomers and interacts with multivalent substrates, and this mediates the formation of condensates. These condensates bear the hallmarks of enzymatic ubiquitination activity. We characterized the effect of mutations in the dimerization domains of SPOP on its linear oligomerization, binding to the substrate DAXX, and phase separation with DAXX. We showed that the mutations reduce SPOP oligomerization and shift the size distribution of SPOP oligomers to smaller sizes. The mutations therefore reduce the binding affinity to DAXX, but enhance the poly-ubiquitination activity of SPOP towards DAXX. This unexpectedly enhanced activity may be explained by enhanced phase separation of DAXX with the SPOP mutants. Our results provide a comparative assessment of the functional role of clusters versus condensates and support a model in which phase separation is an important factor in SPOP function. Our findings also suggest that tuning of linear SPOP self-association could be used by the cell to modulate its activity, and provide insights into the mechanisms underlying hypermorphic SPOP mutations. The characteristics of these cancer-associated SPOP mutations suggest a route for designing separation-of-function mutations in other phase-separating systems.

This paper evaluates the benefits of explicitly integrating online mineral liberation data in control systems for grinding–separation circuits. Although liberation is a critical variable for separation processes, this endeavour has not been attempted mainly because sensors providing continuous online or even at line measurements are yet to be developed. The ore particle size is seen as the key variable influencing mineral liberation. In this study, a phenomenological two-stage comminution circuit simulator previously calibrated from industrial and laboratory data was supplemented with a three-cell flotation line in open circuit. An economic real-time optimisation (RTO) layer coordinates the setpoints of a linear model predictive controller (MPC) of the grinding circuit. Assumed measurable, mineral liberation data feeds the RTO to update the particle size target parameter in an internal model predicting the flotation concentrate mass flow rate, grade, and recovery. Profits, derived from concentrate production rate, grade, and metal recovery, can improve by up to +5% compared with the standard approach, i.e. keeping the flotation feed particle size target constant.

Background The split sleeve cold expansion process is widely used to improve the fatigue life of fastener holes in the civil and military aircraft industry. The process introduces beneficial compressive residual stresses around the processed hole, but uncertainties remain about the character of the stress field immediately adjacent to the bore of the hole. Objective The primary objective of this study was to implement the contour method with minimising error associated with cutting-induced plasticity to provide detailed and reliable characterisation of the residual stress introduced by the split sleeve cold expansion process. Methods A systematic FE study of plasticity effects by simulating different contour cutting strategies (a single cut, two sequential cuts and a 6-cut sequence) for a cold expanded hole in an aluminium alloy coupon was conducted. The identified ‘optimum’ cutting strategy was then applied experimentally on coupons containing a hole that had been processed to 3.16% applied expansion. Results The FE study of different cutting simulations show that the locations of the stress error is consistent with the location where cutting-induced plasticity accumulated and that the magnitude and locations of stress re-distribution plasticity can be controlled by an optimised cutting strategy. In order to validate this hypothesis a high quality contour measurement was performed, showing that accurate near bore stress results can be achieved by the proposed 6-cut approach that controls cutting induced plasticity. Conclusions The present work has demonstrated that detailed FE simulation analysis can be a very effective tool in supporting the development of an optimum cutting sequence and in making correct choices of boundary conditions. Through optimizing these key aspects of the cutting sequence one is much more likely to have a successful, low error contour residual stress result.

Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,000 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the most common type of primary liver cancer, which is the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long noncoding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes, with the subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases.

Toll-like receptors (TLRs) recognize pathogen- and host-derived factors and control immune responses via the adaptor protein MyD88 and members of the interferon regulatory transcription factor (IRF) family. IRFs orchestrate key effector functions, including cytokine release, cell differentiation, and, under certain circumstances, inflammation pathology. Here, we show that IRF activity is generically controlled by the Src kinase family member LYN, which phosphorylates all TLR-induced IRFs at a conserved tyrosine residue, resulting in K48-linked polyubiquitination and proteasomal degradation of IRFs. We further show that LYN activity is controlled by the upstream kinase C-terminal Src kinase (CSK), whose activity, in turn, is controlled by the adaptor protein SPOP, which serves as molecular bridge to recruit CSK into the TLR signaling complex and to activate CSK catalytic activity. Consistently, deletion of SPOP or CSK results in increased LYN activity, LYN-directed IRF degradation, and inhibition of IRF transcriptional activity. Together, the data reveal a key regulatory mechanism for IRF family members controlling TLR biology.

Social economy enterprises (SEEs) are arousing notable interest as promising alternatives where social innovation, business ownership and governance are concerned. In this context, a renewed debate about the internal changes and organizational trajectories experienced by these organizations has emerged in the scholarly literature. This special issue aims to contribute to ongoing debates in this field by advancing our understanding of the external pressures and internal dynamics that can trigger degeneration in SEEs, the conditions and factors that allow SEEs preserving their hallmark values and practices, and the resources and processes of organizational change that SEEs can deploy to overcome degeneration and regenerate. In this editorial introduction we introduce the topic of research, describe the content of the current special issue, and highlight some conclusions and possible directions for future research.

Particle size control in mineral processing is typically achieved using an index characterising the whole distribution, e.g. the sieve opening through which a given mass fraction of the population would pass. Although mineral liberation is the goal of size reduction, its use for monitoring and process control applications is not reported because its online measuring is currently not possible. This paper proposes to address this issue using a mineral liberation distribution estimator consisting in two models. The first one uses a polynomial expression to relate the size-by-size mineralogical distribution of every mineral species to that of the ore. The second model relies on a beta distribution function to sort the masses in every size fraction into liberation classes. The characteristic constants of the beta function are parameterised with the properties of the ore. Results demonstrate that the liberation estimator can represent liberation distributions of both fresh and processed comminution products.

With no doubt, modeling and simulation are powerful tools improving the performance of current optimisation and control strategies. At least in the mineral processing field, however, one of the major gaps in literature is that authors frequently skip specific details on the model calibration methodologies, mainly those concerning data acquisition and processing, calibration sequence, cost function formulation (including constraints), optimisation problem solution, parameter uncertainty, etc. As a contribution to that matter, this paper presents a detailed calibration procedure for a grinding circuit model from plant and laboratory data. The methodology integrates both a global search routine to avoid cost function local minima, and a Jack-knife resampling and recalibration technique to estimate the parameter confidence. The simulator will serve in future work for the coupling of separation processes, and thus the development of plant-wide model-based optimisation and control strategies.

L’innovation sociale et l’economie sociale et solidaire sont au cœur de l’analyse que fait Benoit Levesque du modele quebecois, qui suscite aujourd’hui l’interet partout dans le monde. Ce sociologue a contribue a la reconnaissance d’une vision elargie de l’economie, qui couvre non seulement le secteur prive, mais aussi le secteur public et les initiatives relevant de la societe civile, soit une economie plurielle dont certaines composantes sont orientees vers la democratisation economique. Concu sous la forme d’entretiens avec Benoit Levesque, ce livre permet d’explorer, avec le chercheur, le contexte de sa production scientifique et sa signification pour la societe quebecoise. Il en resulte un genre hybride, ou les elements biographiques se conjuguent a un temoignage personnel et intellectuel, offrant au lecteur un voyage a travers une vie, l’histoire d’une pensee et son influence. Ces conversations nous font decouvrir les particularites du metier d’un sociologue engage et sa vision de l’histoire recente du Quebec, de la Revolution tranquille a aujourd’hui. Ses travaux et ses interventions montrent l’importance du role joue par des acteurs de la societe civile, portee par des organisations collectives souvent orientees vers l’interet general, tels les organismes communautaires, les syndicats, les cooperatives, les entreprises d’economie sociale, et plus recemment le secteur philanthropique et le mouvement ecologiste. L’ouvrage s’interesse aux rapports sociaux, mais il met aussi en valeur les dimensions politiques du modele quebecois. On y decouvre un Etat plus stratege et une societe civile plus politique qu’on le presumait, evoquant un «?socialisme civil?». C’est a partir de tels constats que le sociologue fournit des pistes de reflexion pour penser l’avenir du Quebec, qu’il voit d’ailleurs comme une societe engagee.

Frustulia Rabenhorst is an established diatom genus that is common and widespread across North America. As for many diatom genera, taxa within Frustulia have been the subject of taxonomic confusion...

Background and aims – Confusion over the taxonomic identity of Neidium iridis (Ehrenb.) Cleve (= Navicula iridis Ehrenb.) has persisted for more than 130 years with identifications of valve shapes varying from elliptical to linear and sizes from 100 to 300 µm. This confusion can be linked to the rarity of the species and poor attention to the original line drawings of Ehrenberg. This study examines the type material of Navicula iridis and further uses additional material from North America to define the species Neidium iridis. Methods – Mica and material from Christian Gottfried Ehrenberg’s Collection were studied to examine Navicula iridis. Light and electron microscope techniques were used to document the variability of valve morphology of original material in comparison with other fossil and recent materials. Key results – Ehrenberg designated no nomenclatural type for Navicula iridis at the place of its first description, and until recently the original material was not studied. One freshwater extant locality was identified (New York, West Point) in the original 1843 publication, and in his notes and drawings. Examination of the micas and material from the type locality, showed that Navicula iridis was very rare. Two specimens were found that matched the line drawing presented by Ehrenberg. In addition, we examined Ehrenberg’s original material with SEM, as well as two other localities in North America and present LM and SEM documentation of additional valve forms. A further evaluation of the status of Neidium columnaris, Neidium maximum and an unknown taxon in relation to Neidium iridis is presented. Conclusions – The findings of this study elucidate the taxon Navicula iridis (= Neidium iridis) as described by Ehrenberg in 1843. This will assist in the identification of other large Neidium taxa which to date have been associated with Neidium iridis.

International audience; We report the discovery of a new enveloped, spherical virus belonging to the Phenuiviridae family of negative ssRNA viruses associated with a massive outbreak in a French population of the endangered white-clawed crayfish Austropotamobius pallipes. We call this virus Bunya-like Brown Spot Virus (BBSV) and characterize it using transmission electronic microscopy, genome sequencing and clinical signs. Infected specimens show discolored brown spots on the cuticle. Using RNA-seq data we assembled a partial sequence for the L, M and S genome segments of BBSV. Phylogenetic analyses using all three segments show this virus is closely related to the Wenling crustacean virus 7 (China) and to a bunya-like virus found in feces of the European otter. Our survey of the mass mortality event indicates the virus is less virulent than the crayfish plague caused by Aphanomyces astaci. Overall, the discovery of BBSV provides a new important asset to monitor A. pallipes populations.

In the past few decades, extensive and intensive work has been done in the field of optimisation and control for mineral processing plants. As the valuable minerals have to be separated from the gangue through grinding, one of the most crucial process variables to monitor is the particle size. Although great advances have been accomplished, the vast majority of the proposed strategies relies on the control of a given product size index. The ultimate goal of comminution is mineral liberation, and it is not exclusively dependent on particle dimensions. Approaches focusing on liberation control rather than particle size could thus provide significant advantages. However, online measurement or estimation of mineral liberation is challenging to say the least. In this regard, there is still no work reported in the literature on the use of mineral liberation for online optimisation and control. This article explores the use of a mineral liberation distribution estimator for process control by investigating the effect of changing material properties and plant operating conditions. First, ore characteristics such as size distribution, mineral grades and grain sizes are varied to assess their impact. Then, the estimator is implemented as a liberation sensor in a simulated grinding circuit to observe the effect of modifying operating conditions. The results give a preliminary insight on the possibilities of using mineral liberation information for process control and optimisation purposes.

Background In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. Methods We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. Results A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P Conclusions In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.

Experimentalists are limited in the amount of information they can derive from drop impact experiments on porous surfaces because of the short timescales involved and the normally opaque nature of porous materials. Numerical simulations can supplement experiments and provide researchers with previously unattainable information such as velocity and pressure profiles, and quantification of fluid volume flow rates into the pores. Ethanol drops, 2.0 mm in diameter, are impacted on a narrow gap at Weber numbers that match the impact of water drops, also 2.0 mm in diameter, on the same gap size in a previous study. The experiments show the ethanol drops cleaving at all Weber numbers tested, while the water drops completely enter the gap at low Weber numbers and only cleave at higher Weber numbers. A volume of fluid numerical model of the experiments is constructed in OpenFOAM and used to probe the interior of the drops during impact. For the water drop, a high-pressure region fills the drop during impact which continuously drives liquid into the gap. For the ethanol drops, the high-pressure region is smaller and quickly attenuates, which results in a near-zero vertical velocity at the entrance of the gap. Compared to water, the lower surface tension of ethanol causes these drops to spread further upon impact, recoil less, and overall have less liquid over the gap, which promotes cleaving. Against a superficial thought, when the penetration of liquids into porous materials is to be maximized, a higher surface tension liquid is therefore desirable.

La crisis de salud provocada por la pandemia covid-19 ha afectado de forma global a toda la población mundial y las consecuencias de la misma han sido diferentes en cada país. Como era de esperar, la población más vulnerable ha sufrido las consecuencias más devastadoras con respecto a la salud, desempleo o incremento de la desigualdad. En algunos países la economía informal ha pasado a ser superior a la economía formal. La Economía Social y Solidaria (en adelante ESS) también ha sufrido las consecuencias provocadas por la covid-19, pero también ha sido respuesta a las múltiples situaciones que se han producido en todos los países. El objetivo de este trabajo es examinar el papel de la ESS a nivel internacional atendiendo a dos cuestiones: una, examinar las respuestas de la ESS a la crisis provocada por la pandemia covid-19 y dos, analizar el papel de la ESS en la futura recuperación social y económica. Para ello, se realiza un análisis comparado de las respuestas, estrategias y papel de la ESS en diferentes territorios, Quebec, Colombia y España.

The impact of water droplets on thin porous layers of glass beads held vertically between glass plates was photographed to observe simultaneous spreading and infiltrating of the liquid into the porous medium. Glass beads with diameters of either 100 µm or 500 µm were tested and micro-computed tomography was used to measure the porosities of the layers. The water drop diameter was kept constant at 2 mm while the impact velocity was varied from 0.06, to 1.9 m/s. High-speed videos of the advance of water into the porous structure were studied with image analysis software and the volume flow rate of liquid calculated. Increasing droplet impact velocity decreases droplet infiltration time because higher droplet inertia drives more liquid into the porous material and a larger droplet spreading diameter increases the area in contact with the substrate. Too high of an impact velocity results in droplet cleaving where a portion of the drop remains on the upper surface. A simple model is proposed to determine when inertia driven infiltration will be significant. Once droplet inertia is dissipated capillary forces draw liquid into the substrate and analytical models are compared to predict the rate of capillary driven flow.

The analysis of the spectrum features of thermal desorption spectroscopy (TDS) using the desorption-rate profile against temperature is widely applied to investigate the hydrogen kinetics including diffusion and trapping in metallic materials, which is related to hydrogen embrittlement. Recently the TDS spectrum features such as the peak magnitude and the peak area have been used for qualitative assessment of creep damage, although there is still a lack of theoretical understanding on the correlation between TDS spectrum features and creep damage. In this paper, creep voids inducing creep damage are considered as the only kind of hydrogen traps in steels. The relationships between the TDS spectrum features and creep damage of ferritic steels are investigated through parameter analysis of the modified McNabb-Foster model together with the Oriani assumption, which can describe hydrogen evolution during thermal desorption. It is found that the peak area of TDS spectrum is independent of the trap binding energy, and it is proportional to the trap density, demonstrating that it could be a good indicator for creep damage. The creep damage can be characterized as a power-law function of the peak area of TDS spectrum, indicating TDS as a promising semi-destructive characterization method for creep damage of metallic steels.

Interest in Social Impact Bonds (SIBs) and similar performance-based investments has been spreading around the world ever since the first SIB was issued in the United Kingdom in 2010. At the same time, such investments have given rise to questions regarding the complexity and cost of the contracting mechanisms involved, the possible contradictions between the various objectives pursued, and even the validity of the theoretical premises underpinning them (Albertson et al., 2018a). The objective of this paper is to take stock of the existing knowledge about SIBs and similar performance-based investments, through an overview of recent scientific literature. Relying on a targeted review of the literature and empirical studies, the idea is to compile the arguments that have been mobilized to support, nuance or possibly undermine the implementation of SIBs and similar financing tools. The objective is to provide answers to the question: Do SIBs work? And if yes, under which conditions? After explaining what SIBs are, how they function and how they have developed, the authors propose a synthesis of the arguments from recent scientific literature both supporting and criticizing SIBs. The article concludes that despite the possible improvements and opportunities of these bonds, caution is advised in applying them for as long as empirical evidence is insufficient with regard to their effectiveness and the conditions under which they might be considered appropriate.

Objective As the leading risk factor for the development of liver cancer, chronic infection with hepatitis B virus (HBV) represents a significant global health concern. Although an effective HBV vaccine exists, at least 240 million people are chronically infected with HBV worldwide. Therapeutic options for the treatment of chronic HBV remain limited, and none achieve an absolute cure. To develop novel therapeutic targets, a better understanding of the complex network of virus-host interactions is needed. Because of the central metabolic role of the liver, we assessed the metabolic impact of HBV infection as a means to identify viral dependency factors and metabolic pathways that could serve as novel points of therapeutic intervention. Methods Primary rat hepatocytes were infected with a control adenovirus, an adenovirus expressing a greater-than-unit-length copy of the HBV genome, or an adenovirus expressing the HBV X protein (HBx). A panel of 369 metabolites was analyzed for HBV- or HBx-induced changes 24 and 48 h post infection. Pathway analysis was used to identify key metabolic pathways altered in the presence of HBV or HBx expression, and these findings were further supported through integration of publically available gene expression data. Results We observed distinct changes to multiple metabolites in the context of HBV replication or HBx expression. Interestingly, a panel of 7 metabolites (maltotriose, maltose, myristate [14:0], arachidate [20:0], 3-hydroxybutyrate [BHBA], myo-inositol, and 2-palmitoylglycerol [16,0]) were altered by both HBV and HBx at both time points. In addition, incorporation of data from a transcriptome-based dataset allowed us to identify metabolic pathways, including long chain fatty acid metabolism, glycolysis, and glycogen metabolism, that were significantly altered by HBV and HBx. Conclusions Because the liver is a central regulator of metabolic processes, it is important to understand how HBV replication and HBV protein expression affects the metabolic function of hepatocytes. Through analysis of a broad panel of metabolites we investigated this metabolic impact. The results of these studies have defined metabolic consequences of an HBV infection of hepatocytes and will help to lay the groundwork for novel research directions and, potentially, development of novel anti-HBV therapeutics.

Chronic hepatitis B virus infection is a significant risk factor for cirrhosis and hepatocellular carcinoma. The HBx protein is required for virus replication, but the lack of robust infection models has hindered our understanding of HBx functions that could be targeted for antiviral purposes. We briefly review three properties of HBx: its binding to DDB1 and its regulation of cell survival and metabolism, to illustrate how a single viral protein can have multiple effects in a cell. We propose that different functions of HBx are needed, depending on the changing hepatocyte environment encountered during a chronic virus infection, and that these functions might serve as novel therapeutic targets for inhibiting hepatitis B virus replication and the development of associated diseases.

Depuis 2010, l’Office national de l’eau et des milieux aquatiques (Onema), aujourd’hui integre a l’Agence francaise pour la biodiversite (AFB), les agences de l’eau et leurs partenaires constituent un reseau de sites de demonstration pour la restauration hydromorphologique des cours d’eau. Les sites de demonstration doivent faire l’objet d’un suivi scientifique homogene appele « suivi scientifique minimal » (SSM), ce qui permet d’acquerir des donnees de suivi standardisees sur le long terme et d’etudier les effets des operations de restauration sur le milieu. L’organisation du projet repose sur l’emboitement des echelles d’actions : coordination et cadrage scientifique au niveau national, choix des sites et organisation de la mise en œuvre au niveau des grands bassins hydrographiques, realisation des suivis au niveau local. Sur le territoire metropolitain, le reseau de sites de demonstration compte actuellement une quarantaine de sites potentiels pour un objectif minimum de 60 sites d’ici fin 2018. Dans le cadre d’une strategie globale de suivi de ses operations de restauration de l’hydromorphologie, l’agence de l’eau Rhin-Meuse participe a ce projet en promouvant la mise en œuvre du SSM aupres des porteurs de projets ou en prenant en charge la mise en œuvre des suivis. L’operation de remeandrage du Longeau, portee par le Syndicat intercommunal d’amenagement du Longeau et de la Seigneulle, beneficie ainsi d’un suivi de type SSM. La reussite du reseau de sites de demonstration passe par la bonne articulation entre les differentes echelles de travail et une bonne synergie entre les aspects scientifiques et operationnels du projet. En effet, l’experience de chacun est mise a profit pour alimenter la reflexion generale.

Worldwide, approximately 240 million people are chronically infected with the hepatitis B virus (HBV); chronic HBV infection is associated with the development of life-threatening liver diseases. The HBV HBx protein alters hepatocyte physiology to promote HBV replication. We previously reported that HBx modulates calcium signaling to stimulate HBV replication in human hepatoblastoma HepG2 cells and primary rat hepatocytes. Whether HBx modulates calcium signaling in a primary human hepatocyte, the natural site of an HBV infection, has not been determined. Here, we report the effect of HBx on calcium signaling in primary human hepatocytes and show that HBx modulates calcium signaling via enhanced calcium entry through store-operated calcium channels and elevated mitochondrial calcium, similar to HBx effects in HepG2 cells and primary rat hepatocytes. In addition to demonstrating that HBV and HBx affect calcium signaling in human hepatocytes, these studies also show that HBV and HBx regulation of calcium signaling is identical in primary human and rat hepatocytes, further validating the use of cultured primary rat hepatocytes for HBV studies.