Design Aspects for Portable LED-Based Colorimetric Characterisation Systems Targeting Liquid Analytes.

Colorimetric characterisation systems based on LEDs and RBG sensors are straightforward to implement, are highly integrable allowing for portable measurement systems and can be constructed using widespread and affordable components. They have already proved to be a satisfactory solution in several applications related to chemical analysis. In this paper, we present an RGB sensor-based prototype for colorimetric characterisation, which can accommodate cuvettes with optical paths of 10 mm and 40 mm. We assessed the impact of experimental condition parameters such as the variability of the analyte volume in the cuvette, as well as the presence of floating particles or deposits at the bottom of the cuvette. While these would not impact the result given by a spectrophotometer that generally has a directional light source, they must be considered in LED/RGB sensor analysers in which the light path is not tightly controlled. We demonstrated that there is a minimal sensor height above the bottom of the cuvette and a minimal analyte level (both depending on the prototype optical path length) above which the analyte volume and the presence of floating particles and deposits have no impact on the prototype output signal. Finally, based on these results, we proposed a test method for a quick dye-displacement assay, in which the reagent is a dye-loaded molecularly imprinted polymer that is poured directly into a cuvette.

Package Design Thermal Optimization for Metal-Oxide Gas Sensors by Finite Element Modeling and Infra-Red Imaging Characterization.

We designed a 3D geometrical model of a metal-oxide gas sensor and its custom packaging and used it in finite element modeling (FEM) analysis for obtaining temperature and heat flux distribution. The 3D computer simulation, performed with GetDP software (version 3.5.0, 13 May 2022), accurately predicted the temperature distribution variation across the entire assembly. Knowing the temperature variation and the location of the hot spots allowed us to select the best electrical interconnect method and to choose the optimal materials combination and optimal geometry. The thermal modeling also confirmed the need to use a low thermal conductivity material to insulate the MOX sensor since the latter is heated to its operational temperature of 250 °C. For that purpose, we used the in-house formulated xerogel-epoxy composite of thermal conductivity of 0.108 W m-1 K-1, which is at least 30% less compared to the best-in-class among commercially available materials. Based on the 3D FEM outputs, we designed, assembled, and characterized a fully functional packaged MOX gas sensor in several configurations. We measured the temperature distribution on all parts of the MOX gas sensor assembly using a thermal imaging infrared (IR) microscope. The results of 3D FEM are in good agreement with the temperature distribution obtained by the non-contact IR thermal characterization.

An Interlocked Figure-of-Eight Molecular Shuttle.

Here is reported the synthesis and characterization of an interlocked figure-of-eight rotaxane molecular shuttle from a dibenzo-24-crown-8 (DB24C8) derivative. This latter bears two molecular chains, whose extremities are able to react together by click chemistry. One of the two substituting chain holds an ammonium function aimed at driving the self-entanglement through the complexation of the DB24C8 moiety. In the targeted figure-of-eight rotaxane, shuttling of the DB24C8 along the threaded axle from the best ammonium station to the weaker binding site triazolium was performed through deprotonation or deprotonation-then-carbamoylation of the ammonium. This way, two discrete co-conformational states were obtained, in which the folding and size of the two loops could be changed.

Endoscopic follow-up of low-grade precancerous bronchial lesions in high-risk patients: long-term results of the SELEPREBB randomised multicentre trial.

BACKGROUND: 3-9% of low-grade preinvasive bronchial lesions progress to cancer. This study assessed the usefulness of an intensive bronchoscopy surveillance strategy in patients with bronchial lesions up to moderate squamous dysplasia. METHODS: SELEPREBB (ClinicalTrials.gov NCT00213603) was a randomised study conducted in 17 French centres. After baseline lung computed tomography (CT) and autofluorescence bronchoscopy (AFB) to exclude lung cancer and bronchial severe squamous dysplasia or carcinoma in situ (CIS), patients were assigned to standard surveillance (arm A) with CT and AFB at 36 months or to intensive surveillance (arm B) with AFB every 6 months. Further long-term data were obtained with a median follow-up of 4.7 years. RESULTS: 364 patients were randomised (A: 180, B: 184). 27 patients developed invasive lung cancer and two developed persistent CIS during the study, with no difference between arms (OR 0.63, 95% CI 0.20-1.96, p=0.42). Mild or moderate dysplasia at baseline bronchoscopy was a significant lung cancer risk factor both at 3 years (8 of 74 patients, OR 6.9, 95% CI 2.5-18.9, p<0.001) and at maximum follow-up (16 of 74 patients, OR 5.9, 95% CI 2.9-12.0, p<0.001). Smoking cessation was significantly associated with clearance of bronchial dysplasia on follow-up (OR 0.12, 95% CI 0.01-0.66, p=0.005) and with a reduced risk of lung cancer at 5 years (OR 0.15, 95% CI 0.003-0.99, p=0.04). CONCLUSION: Patients with mild or moderate dysplasia are at very high risk for lung cancer at 5 years, with smoking cessation significantly reducing the risk. Whereas intensive bronchoscopy surveillance does not improve patient outcomes, the identification of bronchial dysplasia using initial bronchoscopy maybe useful for risk stratification strategies in lung cancer screening programmes.

PANTHER: Making genome-scale phylogenetics accessible to all.

Phylogenetics is a powerful tool for analyzing protein sequences, by inferring their evolutionary relationships to other proteins. However, phylogenetics analyses can be challenging: they are computationally expensive and must be performed carefully in order to avoid systematic errors and artifacts. Protein Analysis THrough Evolutionary Relationships (PANTHER; http://pantherdb.org) is a publicly available, user-focused knowledgebase that stores the results of an extensive phylogenetic reconstruction pipeline that includes computational and manual processes and quality control steps. First, fully reconciled phylogenetic trees (including ancestral protein sequences) are reconstructed for a set of "reference" protein sequences obtained from fully sequenced genomes of organisms across the tree of life. Second, the resulting phylogenetic trees are manually reviewed and annotated with function evolution events: inferred gains and losses of protein function along branches of the phylogenetic tree. Here, we describe in detail the current contents of PANTHER, how those contents are generated, and how they can be used in a variety of applications. The PANTHER knowledgebase can be downloaded or accessed via an extensive API. In addition, PANTHER provides software tools to facilitate the application of the knowledgebase to common protein sequence analysis tasks: exploring an annotated genome by gene function; performing "enrichment analysis" of lists of genes; annotating a single sequence or large batch of sequences by homology; and assessing the likelihood that a genetic variant at a particular site in a protein will have deleterious effects.

Back to the Cradle of Cytotherapy: Integrating a Century of Clinical Research and Biotechnology-Based Manufacturing for Modern Tissue-Specific Cellular Treatments in Switzerland.

Empirically studied by Dr. Brown-Séquard in the late 1800s, cytotherapies were later democratized by Dr. Niehans during the twentieth century in Western Switzerland. Many local cultural landmarks around the Léman Riviera are reminiscent of the inception of such cell-based treatments. Despite the discreet extravagance of the remaining heirs of "living cell therapy" and specific enforcements by Swiss health authorities, current interest in modern and scientifically sound cell-based regenerative medicine has never been stronger. Respective progress made in bioengineering and in biotechnology have enabled the clinical implementation of modern cell-based therapeutic treatments within updated medical and regulatory frameworks. Notably, the Swiss progenitor cell transplantation program has enabled the gathering of two decades of clinical experience in Lausanne for the therapeutic management of cutaneous and musculoskeletal affections, using homologous allogeneic cell-based approaches. While striking conceptual similarities exist between the respective works of the fathers of cytotherapy and of modern highly specialized clinicians, major and important iterative updates have been implemented, centered on product quality and risk-analysis-based patient safety insurance. This perspective article highlights some historical similarities and major evolutive differences, particularly regarding product safety and quality issues, characterizing the use of cell-based therapies in Switzerland over the past century. We outline the vast therapeutic potential to be harnessed for the benefit of overall patient health and the importance of specific scientific methodological aspects.

Reactome and the Gene Ontology: digital convergence of data resources.

MOTIVATION: Gene Ontology Causal Activity Models (GO-CAMs) assemble individual associations of gene products with cellular components, molecular functions and biological processes into causally linked activity flow models. Pathway databases such as the Reactome Knowledgebase create detailed molecular process descriptions of reactions and assemble them, based on sharing of entities between individual reactions into pathway descriptions. RESULTS: To convert the rich content of Reactome into GO-CAMs, we have developed a software tool, Pathways2GO, to convert the entire set of normal human Reactome pathways into GO-CAMs. This conversion yields standard GO annotations from Reactome content and supports enhanced quality control for both Reactome and GO, yielding a nearly seamless conversion between these two resources for the bioinformatics community. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PANTHER version 16: a revised family classification, tree-based classification tool, enhancer regions and extensive API.

PANTHER (Protein Analysis Through Evolutionary Relationships, http://www.pantherdb.org) is a resource for the evolutionary and functional classification of protein-coding genes from all domains of life. The evolutionary classification is based on a library of over 15,000 phylogenetic trees, and the functional classifications include Gene Ontology terms and pathways. Here, we analyze the current coverage of genes from genomes in different taxonomic groups, so that users can better understand what to expect when analyzing a gene list using PANTHER tools. We also describe extensive improvements to PANTHER made in the past two years. The PANTHER Protein Class ontology has been completely refactored, and 6101 PANTHER families have been manually assigned to a Protein Class, providing a high level classification of protein families and their genes. Users can access the TreeGrafter tool to add their own protein sequences to the reference phylogenetic trees in PANTHER, to infer evolutionary context as well as fine-grained annotations. We have added human enhancer-gene links that associate non-coding regions with the annotated human genes in PANTHER. We have also expanded the available services for programmatic access to PANTHER tools and data via application programming interfaces (APIs). Other improvements include additional plant genomes and an updated PANTHER GO-slim.

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds-Mechanistic Insights.

We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated ß-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N'-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated ß-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson's. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.

Ancestral Genomes: a resource for reconstructed ancestral genes and genomes across the tree of life.

A growing number of whole genome sequencing projects, in combination with development of phylogenetic methods for reconstructing gene evolution, have provided us with a window into genomes that existed millions, and even billions, of years ago. Ancestral Genomes (http://ancestralgenomes.org) is a resource for comprehensive reconstructions of these 'fossil genomes'. Comprehensive sets of protein-coding genes have been reconstructed for 78 genomes of now-extinct species that were the common ancestors of extant species from across the tree of life. The reconstructed genes are based on the extensive library of over 15 000 gene family trees from the PANTHER database, and are updated on a yearly basis. For each ancestral gene, we assign a stable identifier, and provide additional information designed to facilitate analysis: an inferred name, a reconstructed protein sequence, a set of inferred Gene Ontology (GO) annotations, and a 'proxy gene' for each ancestral gene, defined as the least-diverged descendant of the ancestral gene in a given extant genome. On the Ancestral Genomes website, users can browse the Ancestral Genomes by selecting nodes in a species tree, and can compare an extant genome with any of its reconstructed ancestors to understand how the genome evolved.

The Importance of Length and Flexibility of Macrocycle-Containing Molecular Translocators for the Synthesis of Improbable [2]Rotaxanes.

This work reports on the use of molecular translocators to capture a dibenzo-24-crown-8 (DB24C8) and then release it onto targeted molecular axles to afford, after removal of the translocator, [2]rotaxanes that do not hold any template site. Various translocators were studied and successfully aided the synthesis, with more or less efficacy, of [2]rotaxanes of different lengths. During the releasing step, the DB24C8 macrocycle shuttles along the thread, and the localization of the macrocycle might be driven by steric repulsion on the translocator part and/or electronic attraction of the targeted part of the axle to be encircled, which depends on both the nature of the translocator and the targeted thread to be encircled.

Insecticidal Activity of the Leaf Essential Oil of Peperomia borbonensis Miq. (Piperaceae) and Its Major Components against the Melon Fly Bactrocera cucurbitae (Diptera: Tephritidae).

The essential oil from the leaves of Peperomia borbonensis from Réunion Island was obtained by hydrodistillation and characterized using GC-FID, GC/MS and NMR. The main components were myristicin (39.5%) and elemicin (26.6%). The essential oil (EO) of Peperomia borbonensis and its major compounds (myristicin and elemicin), pure or in a mixture, were evaluated for their insecticidal activity against Bactrocera cucurbitae (Diptera: Tephritidae) using a filter paper impregnated bioassay. The concentrations necessary to kill 50% (LC50 ) and 90% (LC90 ) of the flies in three hours were determined. The LC50 value was 0.23 ± 0.009 mg/cm2 and the LC90 value was 0.34 ± 0.015 mg/cm2 for the EO. The median lethal time (LT50 ) was determined to compare the toxicity of EO and the major constituents. The EO was the most potent insecticide (LT50  = 98 ± 2 min), followed by the mixture of myristicin and elemicin (1.4:1) (LT50  = 127 ± 2 min) indicating that the efficiency of the EO is potentiated by minor compounds and emphasizing one of the major assets of EOs against pure molecules.

Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine.

Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species.

Nine µg intradermal influenza vaccine and 15 µg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults.

Intanza® 9 µg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 µg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 µg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 µg (n=38) or IM 15 µg (n=42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 µg vaccine are similar to those to the standard IM 15 µg vaccine.

Hysteresis prediction inside magnetic shields and application.

We have developed a simple model that is able to describe and predict hysteresis behavior inside Mumetal magnetic shields, when the shields are submitted to ultra-low frequency (<0.01 Hz) magnetic perturbations with amplitudes lower than 60 µT. This predictive model has been implemented in a software to perform an active compensation system. With this compensation the attenuation of longitudinal magnetic fields is increased by two orders of magnitude. The system is now integrated in the cold atom space clock called PHARAO. The clock will fly onboard the International Space Station in the frame of the ACES space mission.

Results of a human factors experiment of the usability and patient acceptance of a new autoinjector in patients with rheumatoid arthritis.

PURPOSE: This study evaluated the human factors affecting the ease of use of a disposable autoinjector developed for subcutaneous self-injections performed by patients with chronic diseases. MATERIALS AND METHODS: This was a randomized, single-center study conducted with 65 patients with rheumatoid arthritis. Patients performed six simulated injections. Assessments of patient device acceptance and device usability were made by patient reports and independent observations of compliance with the device instruction for use (IFU) following single injections and repeated injections. RESULTS: A total of 390 simulated injections were performed. Patient device acceptance was high; more than 90% of patients found each of the tested criteria to be acceptable (>80% was required for statistical significance; P<0.016). Perceived ease of use and simplicity of the three-step process resulted in high acceptance scores: mean scores (± standard deviation) were 8.71 (±1.18) and 8.05 (±0.37), respectively, on a 0-10-point scale. Patients also expressed their acceptance with the ease and usefulness of the detection of the remaining drug in the autoinjector. In addition, 80% of patients declared that they would recommend the device to someone else. Globally, the human factors tested (age, sex, hand disability [Cochin score], extent of previous experience with self-injection [ie, expert or naïve]) had no impact on IFU device compliance. In particular, the lack of a Cochin score interaction indicated that the degree of hand disability is not a predictive factor of poor self-injection capability with this autoinjector. CONCLUSION: This study demonstrated a high level of patient acceptance for self-injection with this autoinjector among patients with rheumatoid arthritis. In particular, patients with severe hand disability were able to successfully comply with device IFU.

Comparative histology and immunohistochemistry of porcine versus human skin.

BACKGROUND: Porcine skin is increasingly being employed as a model of human skin in various research fields, including pharmacology, toxicology and immunology, with particular interest in percutaneous permeation and organ transplantation. Porcine skin shows several anatomical and physiological similarities, but also some differences, with human skin, but few in depth comparative studies are so far available. OBJECTIVES: To study the immunohistochemical properties of normal porcine skin in comparison with human skin. MATERIALS AND METHODS: We performed a histological and immunohistochemical study on frozen and formalin-fixed, paraffin-embedded skin biopsies from domestic swine and normal human skin, using a panel of 93 monoclonal or polyclonal antibodies recognizing various human and porcine skin cell types or structures. RESULTS: We found that several antibodies used to detect normal human skin cells showed equivalent immunoreactivity on normal porcine skin. However, some antibodies commonly used to detect human skin antigens remained unreactive on porcine skin. CONCLUSIONS: Our findings highlight the main immunohistochemical properties of porcine skin in comparison with those of human skin and provide a morphological and immunohistochemical basis useful to researchers using porcine skin.

Precision measurement of the hydrogen 1S-2S frequency via a 920-km fiber link.

We have measured the frequency of the extremely narrow 1S-2S two-photon transition in atomic hydrogen using a remote cesium fountain clock with the help of a 920 km stabilized optical fiber. With an improved detection method we obtain f(1S-2S)=2466 061 413 187 018 (11) Hz with a relative uncertainty of 4.5×10(-15), confirming our previous measurement obtained with a local cesium clock [C. G. Parthey et al., Phys. Rev. Lett. 107, 203001 (2011)]. Combining these results with older measurements, we constrain the linear combinations of Lorentz boost symmetry violation parameters c((TX))=(3.1±1.9)×10(-11) and 0.92c((TY))+0.40c((TZ))=(2.6±5.3)×10(-11) in the standard model extension framework [D. Colladay, V. A. Kostelecký, Phys. Rev. D. 58, 116002 (1998)].