Solvay (Belgium)

Organic and printed electronics technologies require conductors with a work function that is sufficiently low to facilitate the transport of electrons in and out of various optoelectronic devices. We show that surface modifiers based on polymers containing simple aliphatic amine groups substantially reduce the work function of conductors including metals, transparent conductive metal oxides, conducting polymers, and graphene. The reduction arises from physisorption of the neutral polymer, which turns the modified conductors into efficient electron-selective electrodes in organic optoelectronic devices. These polymer surface modifiers are processed in air from solution, providing an appealing alternative to chemically reactive low-work function metals. Their use can pave the way to simplified manufacturing of low-cost and large-area organic electronic technologies.

Animal models are commonly used in the preclinical development of new drugs to predict the metabolic behaviour of new compounds in humans. It is, however, important to realise that humans differ from animals with regards to isoform composition, expression and catalytic activities of drug-metabolising enzymes. In this review the authors describe similarities and differences in this respect among the different species, including man. This may be helpful for drug researchers to choose the most relevant animal species in which the metabolism of a compound can be studied for extrapolating the results to humans. The authors focus on CYPs, which are the main enzymes involved in numerous oxidative reactions and often play a critical role in the metabolism and pharmacokinetics of xenobiotics. In addition, induction and inhibition of CYPs are compared among species. The authors conclude that CYP2E1 shows no large differences between species, and extrapolation between species appears to hold quite well. In contrast, the species-specific isoforms of CYP1A, -2C, -2D and -3A show appreciable interspecies differences in terms of catalytic activity and some caution should be applied when extrapolating metabolism data from animal models to humans.

We have examined an optimization approach to iterative control design. The important ingredient is that the gradient of the design criterion is computed from measured closed loop data. The approach is thus not model-based. The scheme converges to a stationary point of the design criterion under the assumption of boundedness of the signals in the loop. From a practical viewpoint, the scheme offers several advantages. It is straightforward to apply. It is possible to control the rate of change of the controller in each iteration. The objective can be manipulated between iterations in order to tighten or loosen performance requirements. Certain frequency regions can be emphasized if desired. This direct optimal tuning algorithm is particularly well suited for the tuning of the basic control loops in the process industry, which are typically PID loops. These primary loops are often very badly tuned, making the application of more advanced (for example, multivariable) techniques rather useless. A first requirement in the successful application of advanced control techniques is that the primary loops be tuned properly. This new technique appears to be a very practical way of doing this, with an almost automatic procedure.

Obesity is associated with metabolic alterations related to glucose homeostasis and cardiovascular risk factors. These metabolic alterations are associated with low-grade inflammation that contributes to the onset of these diseases. We and others have provided evidence that gut microbiota participates in whole-body metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders. Recently, we defined gut microbiota-derived lipopolysaccharide (LPS) (and metabolic endotoxemia) as a factor involved in the onset and progression of inflammation and metabolic diseases. In this review, we discuss mechanisms involved in the development of metabolic endotoxemia such as the gut permeability. We also discuss our latest discoveries demonstrating a link between the gut microbiota, endocannabinoid system tone, leptin resistance, gut peptides (glucagon-like peptide-1 and -2), and metabolic features. Finally, we will introduce the role of the gut microbiota in specific dietary treatments (prebiotics and probiotics) and surgical interventions (gastric bypass).

An emerging subfield of strategic management is that dealing with the natural environment as it affects corporate strategy. To analyze this we organize the literature on environmental regulations and corporate strategy into a new managerial framework. Next we develop a resource-based view of the interaction between firm-level competitiveness and environmental regulations, including the conditions for the use of green capabilities. Finally, we analyze the green capabilities of multinational enterprises within a standard international business model, using firm-specific advantages (FSAs) and country-specific advantages (CSAs). We then use this FSA/CSA configuration to explore hypotheses on environmental regulations, competitiveness, and corporate strategy. © 1998 John Wiley & Sons, Ltd.

A novel strategy to direct the oxygen reduction reaction to preferentially produce H(2)O(2) is formulated and evaluated. The approach combines the inertness of Au nanoparticles toward oxidation, with the improved O(2) sticking probability of isolated transition metal "guest" atoms embedded in the Au "host". DFT modeling was employed to screen for the best alloy candidates. Modeling indicates that isolated alloying atoms of Pd, Pt, or Rh placed within the Au surface should enhance the H(2)O(2) production relative to pure Au. Consequently, Au(1-x)Pd(x) nanoalloys with variable Pd content supported on Vulcan XC-72 were prepared to investigate the predicted selectivity toward H(2)O(2) production for Au alloyed with Pd. It is demonstrated that increasing the Pd concentration to 8% leads to an increase of the electrocatalytic H(2)O(2) production selectivity up to nearly 95%, when the nanoparticles are placed in an environment compatible with that of a proton exchange membrane. Further increase of Pd content leads to a drop in H(2)O(2) selectivity, to below 10% for x = 0.5. It is proposed that the enhancement in H(2)O(2) selectivity is caused by the presence of individual surface Pd atoms surrounded by gold, whereas surface ensembles of contiguous Pd atoms support H(2)O formation. The results are discussed in the context of exergonic electrocatalytic H(2)O(2) synthesis in Polymer Electrolyte Fuel Cells for the simultaneous cogeneration of chemicals and electricity, the latter a credit to production costs.

Previous studies have found that importing goods from R&D-intensive countries raises a country's productivity. In this paper, we investigate econometrically whether foreign direct investment (FDI) also transfers technology across borders. The data indicates that FDI transfers technology, but only in one direction: a country's productivity is increased if it invests in R&D-intensive foreign countries—particularly in recent years—but not if foreign R&D-intensive countries invest in it. Other findings of the paper are that the ratio of foreign-R&D benefits conveyed by outward FDI to foreign R&D benefits conveyed by imports is higher for large countries than it is for small ones, that failure to account for international R&D spillovers leads to upwardly biased estimates of the output elasticity of the domestic R&D capital stock, and that there are much larger transfers of technology from the United States to Japan than there are from Japan to the United States.

The 20 years following the introduction of the seminal construct of absorptive capacity (AC) by Cohen and Levinthal (Cohen, W. M., D. A. Levinthal. 1989. Innovation and learning: The two faces of R&D. Econom. J. 99(397) 569–596; Cohen, W. M., D. A. Levinthal. 1990. Absorptive capacity: A new perspective on learning and innovation. Admin. Sci. Quart. 35(1) 128–152) have seen the proliferation of a vast literature citing the AC construct in over 10,000 published papers, chapters, and books, and interpreting it or applying it in many areas of organization science research, including organization theory, strategic management, and economics. However, with very few exceptions, the specific organizational routines and processes that constitute AC capabilities remain a black box. In this paper, we propose a routine-based model of AC as a first step toward the operationalization of the AC construct. Our intent is to direct attention to the importance of balancing internal knowledge creating processes with the identification, acquisition, and assimilation of new knowledge originating in the external environment. We decompose the construct of AC into two components, internal and external AC capabilities, and identify the configuration of metaroutines underlying these two components. These higher-level routines are expressed within organizations by configurations of empirically observable practiced routines that are idiosyncratic and firm specific. Therefore, we conceptualize metaroutines as the foundations of practiced routines. The ability of organizations to discover and implement complementarities between AC routines may explain why some firms are successful early adopters and most firms are imitators. Success as an early adopter of a new management practice or an innovation is expected to depend on the extent to which an organization evolves, adapts, and implements the configuration of its internal and external absorptive capacity routines.

We empirically test the prediction of Pástor et al. (2021) that green firms outperform brown firms when concerns about climate change increase unexpectedly, using data for S&P 500 companies from January 2010 to June 2018. To capture unexpected increases in climate change concerns, we construct a daily Media Climate Change Concerns index using news about climate change published by major U.S. newspapers and newswires. We find that on days with an unexpected increase in climate change concerns, the green firms’ stock prices tend to increase, whereas brown firms’ prices decrease. Furthermore, using topic modeling, we conclude that this effect holds for concerns about both transition and physical climate change risk. Finally, we decompose returns into cash flow and discount rate news components and find that an unexpected increase in climate change concerns is associated with an increase (decrease) in the discount rate of brown (green) firms. This paper was accepted by George Serafeim, Special Section of Management Science on Business and Climate Change. Funding: This work was supported by the National Bank of Belgium, Research Foundation Flanders (FWO), Institut de Valorisation des Données (IVADO), the Natural Sciences and Engineering Research Council of Canada [Grant RGPIN-2022-03767], and Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Grants 179281, 191730]. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2022.4636 .

The close empirical connections between populism and nationalism have naturalised a rather misleading overlap between the concepts of populism and nationalism in academic and public debates. As a result, the relation between the two has not received much systematic attention. Drawing on the poststructuralist discourse theory originally formulated by Laclau and Mouffe, this article differentially identifies populism and nationalism as distinct ways of discursively constructing and claiming to represent “the people”, as underdog and as nation respectively. These distinct constructions of “the people” can also be identified and highlighted from a spatial or orientational perspective, by looking at the architectonics of populism and nationalism as revolving around a down/up (vertical) and an in/out (horizontal) axis respectively. Building on this framework, the article then concludes that the co-occurrence of populism and nationalism should be studied through the prism of articulation. Again, a focus on discursive architectonics allows grasping how different political projects construct different discourses by connecting the building blocks of populism and nationalism in particular ways. The study of these articulations, based on a clear distinction between populism and nationalism, is a necessary step in further deepening our understanding of the complexity and variety of populist politics.

Pickering emulsions are surfactant-free dispersions of two immiscible fluids that are kinetically stabilized by colloidal particles. For ecological reasons, these systems have undergone a resurgence of interest to mitigate the use of synthetic surfactants and solvents. Moreover, the use of colloidal particles as stabilizers provides emulsions with original properties compared to surfactant-stabilized emulsions, microemulsions, and micellar systems. Despite these specific advantages, the application of Pickering emulsions to catalysis has been rarely explored. This Minireview describes very recent examples of hybrid and composite amphiphilic materials for the design of interfacial catalysts in Pickering emulsions with special emphasis on their assets and challenges for industrially relevant biphasic reactions in fine chemistry, biofuel upgrading, and depollution.

PURPOSE: Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1(R132MUT)) is frequent in low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, regardless of clinical history. To determine how GBMs arising with IDH1(R132MUT) differ from other GBMs, we undertook a comprehensive comparison of patients presenting clinically with primary GBM as a function of IDH1(R132) mutation status. PATIENTS AND METHODS: In all, 618 treatment-naive primary GBMs and 235 lower-grade diffuse gliomas were sequenced for IDH1(R132) and analyzed for demographic, radiographic, anatomic, histologic, genomic, epigenetic, and transcriptional characteristics. RESULTS: Investigation revealed a constellation of features that distinguishes IDH1(R132MUT) GBMs from other GBMs (including frontal location and lesser extent of contrast enhancement and necrosis), relates them to lower-grade IDH1(R132MUT) gliomas, and supports the concept that IDH1(R132MUT) gliomas arise from a neural precursor population that is spatially and temporally restricted in the brain. The observed patterns of DNA sequence, methylation, and copy number alterations support a model of ordered molecular evolution of IDH1(R132MUT) GBM in which the appearance of mutant IDH1 protein is an initial event, followed by production of p53 mutant protein, and finally by copy number alterations of PTEN and EGFR. CONCLUSION: Although histologically similar, GBMs arising with and without IDH1(R132MUT) appear to represent distinct disease entities that arise from separate cell types of origin as the result of largely nonoverlapping sets of molecular events. Optimal clinical management should account for the distinction between these GBM disease subtypes.

Abstract This paper presents estimates of the long‐term impact of various sources of knowledge (R&D performed by the business sector, the public sector and foreign firms) on multifactor productivity growth of 16 countries from 1980 to 1998. The main results show that the three sources of knowledge are significant determinants of long‐term productivity growth. Further evidence suggests that several factors determine the extent to which each source of knowledge contributes to productivity growth. These factors are the absorptive capability, the origin of funding, the socioeconomic objectives of government support, and the type of public institutions that perform R&D.

The γ-lactam moiety is present in a large number of natural and non-natural biologically active compounds. The range of biological activities covered by these compounds is very broad. Functionalized γ-lactams are thus of high interest and have great potential in medicinal chemistry. This review provides a description of the title compounds by focusing on their synthesis, natural sources and biological activities.

This paper attempts to quantify the aggregate net effect of government funding on business R&D in 17 OECD Member countries over the past two decades. Grants, procurement, tax incentives and direct performance of research (in public laboratories or universities) are the major policy tools in the field. The major results of the study are the following: Direct government funding of R&D performed by firms has a positive effect on business financed R&D (except if the funding is targeted towards defence activities). Tax incentives have an immediate and positive effect on business-financed R&D; Direct funding as well as tax incentives are more effective when they are stable over time: firms do not invest in additional R&D if they are uncertain of the durability of the government support; Direct government funding and R&D tax incentives are substitutes: increased intensity of one reduces the effect of the other on business R&D; The stimulating effect of government funding varies with respect to its generosity: it increases up to a certain threshold (about 10% of business R&D) and then decreases beyond; Defence research performed in public laboratories and universities crowds out private R&D; Civilian public research is neutral for business R&D. * We thank the participants to various seminars, including the OECD Committee for Scientific and Technology Policy and the NBER 2000 Summer Institute on Productivity for helpful comments and suggestions. All opinions expressed in this article are those of the authors and do not reflect necessarily the views of the OECD or Universite Libre de Bruxelles.

BACKGROUND: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist. METHODS: A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II-IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths. FINDINGS: An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (-18.8% from baseline) vs. placebo (+6.9%). INTERPRETATION: Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.

ABSTRACT The blood‐brain barrier (BBB) prevents the entrance of circulating molecules and immune cells into the central nervous system. The barrier is formed by specialized brain endothelial cells that are interconnected by tight junctions (TJ). A defective function of the BBB has been described for a variety of neuroinflammatory diseases, indicating that proper regulation is essential for maintaining brain homeostasis. Under pathological conditions, reactive oxygen species (ROS) significantly contribute to BBB dysfunction and inflammation in the brain by enhancing cellular migration. However, a detailed study about the molecular mechanism by which ROS alter BBB integrity has been lacking. Here we demonstrate that ROS alter BBB integrity, which is paralleled by cytoskel‐eton rearrangements and redistribution and disappearance of TJ proteins claudin‐5 and occludin. Specific signaling pathways, including RhoA and PI3 kinase, mediated observed processes and specific inhibitors of these pathways prevented ROS‐induced monocyte migration across an in vitro model of the BBB. Interestingly, these processes were also mediated by protein kinase B (PKB/ Akt), a previously unknown player in cytoskeleton and TJ dynamics that acted downstream of RhoA and PI3 kinase. Our study reveals new insights into molecular mechanisms underlying BBB regulation and provides novel opportunities for the treatment of neuroinflammatory diseases.—Schreibelt, G., Kooij, G., Reijerkerk, A., van Doorn, R., Gringhuis, S. I., van der Pol, S., Weksler, B. B., Romero, I. A., Couraud, P.‐O., Piontek, J., Blasig, I. E., Dijkstra, C. D., Ronken, E., de Vries, H. E. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase and PKB signaling. FASEB J. 21, 3666–3676 (2007)

OBJECTIVE To determine the prevalence of subnormal testosterone concentrations in patients with obesity and with type 2 diabetes in a primary care clinic population. RESEARCH DESIGN AND METHODS Free testosterone concentrations of 1,849 men (1,451 nondiabetic and 398 diabetic) in the Hypogonadism In Males (HIM) study were analyzed. The HIM study was a U.S.-based cross-sectional study designed to define the prevalence of hypogonadism in men aged >45 years. Free testosterone was measured by equilibrium dialysis. RESULTS The prevalence of subnormal free testosterone concentrations in lean, overweight, and obese nondiabetic men was 26% (n = 275), 29% (n = 687), and 40% (n = 489), respectively (P < 0.001 for trend), and 44% (n = 36), 44% (n = 135), and 50% (n = 227), respectively, in diabetic men (P = 0.46 for trend within group and P < 0.05 compared with nondiabetic men). The mean free testosterone concentration of diabetic men was significantly lower than that of nondiabetic men. Free testosterone concentrations were negatively and significantly (P < 0.001) related to age (r = −0.37), BMI (r = −0.18), and sex hormone–binding globulin (r = −0.11) in multiple regression analysis. The average decline of free testosterone concentrations was 7.8 pg/ml per decade in nondiabetic men and 8.4 pg/ml per decade in diabetic men. CONCLUSIONS Forty percent of obese nondiabetic men and 50% of obese diabetic men aged ≥45 years have subnormal free testosterone concentrations. In view of its high prevalence, obesity is probably the condition most frequently associated with subnormal free testosterone concentrations in males. The concomitant presence of diabetes is associated with an additional increase in the prevalence of subnormal free testosterone concentrations.

PURPOSE: Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality. METHODS: Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death. RESULTS: The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2). CONCLUSION: The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.

When deformed beyond their elastic limits, crystalline solids flow plastically via particle rearrangements localized around structural defects. Disordered solids also flow, but without obvious structural defects. We link structure to plasticity in disordered solids via a microscopic structural quantity, "softness," designed by machine learning to be maximally predictive of rearrangements. Experimental results and computations enabled us to measure the spatial correlations and strain response of softness, as well as two measures of plasticity: the size of rearrangements and the yield strain. All four quantities maintained remarkable commonality in their values for disordered packings of objects ranging from atoms to grains, spanning seven orders of magnitude in diameter and 13 orders of magnitude in elastic modulus. These commonalities link the spatial correlations and strain response of softness to rearrangement size and yield strain, respectively.