Discovery of Heterocyclic Nonacetamide Synaptic Vesicle Protein 2A (SV2A) Ligands with Single‐Digit Nanomolar Potency: Opening Avenues towards the First SV2A Positron Emission Tomography (PET) Ligands

The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non‐acetamide lead compounds, UCB‐A, UCB‐H and UCB‐J, the first single‐digit nanomolar SV2A ligands with suitable properties for development as PET tracers.     

Ester-functionalized poly(3-alkylthiophene) copolymers: Synthesis,physicochemical characterization and performance in bulk heterojunction organic solar cells

The introduction of functional moieties in the donor polymer (side chains) offers a potential pathway toward selective modification of the nanomorphology of conjugated polymer:fullerene active layer blends applied in bulk heterojunction organic photovoltaics, pursuing morphology control and solar cell stability. For this purpose, two types of poly(3-alkylthiophene) random copolymers, incorporating different amounts (10/30/50%) of ester-functionalized side chains, were efficiently synthesized using the Rieke method. The solar cell performance of the functionalized copolymers was evaluated and compared to the pristine P3HT:PCBM system. It was observed that the physicochemical and opto-electronic characteristics of the polythiophene donor material can be modified to a certain extent via copolymerization without (too much) jeopardizing the OPV efficiency, as far as the functionalized side chains are introduced in a moderate ratio (<30%) and that preference is given to side chains with a small molar volume. A range of complementary techniques – UV–Vis spectroscopy, (modulated temperature) differential scanning calorimetry, transmission electron microscopy and X-ray diffraction analysis – indicated that variations in polymer crystallinity, while maintaining a high level of regioregularity, are probably the main factor responsible for the observed differences.     

Survey of 1012 moldy dwellings by culture fungal analysis: Threshold proposal for asthmatic patient management

Different countries have tried to define guidelines to quantify what levels of fungi are considered as inappropriate for housing. This retrospective study analyzes indoor fungi by cultures of airborne samples from 1012 dwellings. Altogether, 908 patients suffering from rhinitis, conjunctivitis, and asthma were compared to 104 controls free of allergies. Portuguese decree law no 118/2013 (PDL118), ANSES (a French environmental and health agency) recommendations, and health regulations of Besançon University Hospital were applied to determine the rates of non‐conforming dwellings, which were respectively 55.2%, 5.2%, and 19%. Environmental microbiological results and medical data were compared. The whole number of colonies per cubic meter of air was correlated with asthma (P < 0.001) and rhinitis (P = 0.002). Sixty‐seven genera and species were detected in bedrooms. Asthma was correlated to Aspergillus versicolor (P = 0.004) and Cladosporium spp. (P = 0.02). Thresholds of 300 cfu/m³ for A. versicolor or 495 cfu/m³ for Cladosporium spp. are able to discriminate 90% of the asthmatic dwellings. We propose a new protocol to obtain an optimal cost for indoor fungi surveys, excluding surface analyses, and a new guideline to interpret the results based on >1000 cfu/m³ of whole colonies and/or above threshold levels for A. versicolor or Cladosporium spp.     

Ambidextrous strategy and execution in entrepreneurial project-oriented organizations: The case of Pagani supercars

This research explores the dynamics underpinning entrepreneurial project-oriented organizations. Specifically, it focuses on how strategy and execution by projects are managed and how ambidexterity – a firm's ability to exploit old certainties while exploring new possibilities – operates as a logic. The empirical findings from an explorative longitudinal research of supercar maker Pagani Automobili in the period 2007–2019, offer an insight of a complex entrepreneurially led project-oriented organization and suggest three integrative mechanisms that describe the ambidextrous management of the interplay within and between strategy and project levels. Additionally, this research recognizes the critical role of projects also in entrepreneurial environments and suggests that the accomplishment of ambidexterity is unique in nature as it is aimed at reconciling the uniqueness of competitive propositions and that of projects within a unique entrepreneurial environment, opening avenues for more theoretical and empirical studies at the intersection of project management and entrepreneurship.     

Capture of carbon dioxide by an ion-exchange resin: Influence of gas humidity on capture mechanisms

This paper evaluates moisture content effects on CO₂ capture of an ion-exchange resin (IER) functionalised with a primary amine group. IER capacities were determined by breakthrough with an inlet gas containing 10 vol% CO₂, nitrogen and various moisture contents. Three types of behaviour were identified according to humidity level. In saturated air conditions, the stoichiometry could be justified by carbonates and bicarbonates fixation. In dry conditions, we suspect a joint physical adsorption and reaction mechanism. For intermediate humidity, the stoichiometry of 1 CO₂ for 1 amine group is consistent with a bicarbonate fixation or carbamic acid formation.     

Planning Belgian Congo’s network of medical infrastructure: type-plans as tools to construct a medical model-colony, 1949–1959

ABSTRACT

Throughout the 1950s, the Belgian colonial government constructed a vast network of hospital infrastructure as part of its Ten-Year Plan, a colony-wide socio-economic scheme emblematic for the era of ‘welfare colonialism.’ This network played a key role in Belgian colonialism, by providing healthcare, but also by boosting labour productivity, facilitating state presence and control, and by advertising Congo as a medical model-colony. In this article, we unpack the extensive administrative apparatus that was necessary to buttress this ambitious building programme, and we highlight type-plans as crucial government tools to construct such a vast network of healthcare infrastructure. At first glance, the use of type-plans confirms classic characterizations of the Belgian colonial government as an omnipotent and technocratic state apparatus that implemented large, top-down government plans through authoritative methods, often discarding local realities. However, tracing hospital construction on the ground reveals that type-plans did not function as immutable models, but rather as modular blueprints that allowed local administrations to adapt hospitals to local needs and contingencies. As such, our article illustrates how, facilitated by surprisingly flexible type-plans, everyday colonial policymaking in Belgian Congo was, contrary to the still dominant discourse, deeply reliant on the agency and aptitude of local officials.     

Acute Generalized Exanthematous Pustulosis: Pathogenesis,Genetic Background,Clinical Variants and Therapy

Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids.