In recent years, vibrational spectroscopic techniques based on Fourier transform infrared (FTIR) or Raman microspectroscopy have been suggested to fulfill the unmet need for microplastic particle ...detection and identification. Inter-system comparison of spectra from reference polymers enables assessing the reproducibility between instruments and advantages of emerging quantum cascade laser-based optical photothermal infrared (O-PTIR) spectroscopy. In our work, IR and Raman spectra of nine plastics, namely polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polycarbonate, polystyrene, silicone, polylactide acid and polymethylmethacrylate were simultaneously acquired using an O-PTIR microscope in non-contact, reflection mode. Comprehensive band assignments were presented. We determined the agreement of O-PTIR with standalone attenuated total reflection FTIR and Raman spectrometers based on the hit quality index (HQI) and introduced a two-dimensional identification (2D-HQI) approach using both Raman- and IR-HQIs. Finally, microplastic particles were prepared as test samples from known materials by wet grinding, O-PTIR data were collected and subjected to the 2D-HQI identification approach. We concluded that this framework offers improved material identification of microplastic particles in environmental, nutritious and biological matrices.
To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed ...clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.
The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.
Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP.
Purpose
This study aims to understand the lasting relationship between luxury fashion and art. The purpose of the paper is to explore whether the application of art, the cooperation with artists, the ...implementation of experiential strategies focusing on retail spaces and shows embedded in the strategic concept of a luxury brand lead to a competitive advantage and to a sustained value creation for luxury brands.
Design/methodology/approach
Based on the literature, the strategic role of art and the importance of experiential marketing for the value creation of European luxury fashion brands was explored through empirical data collection, consisting of 26 semi-structured in-depth interviews. The gained data have been analysed through a thematic analysis approach and triangulated to avoid bias.
Findings
The exploratory study revealed that when art is applied as a strategic tool, it is of relevance to achieve an authentic fit to the brand. When integrating art consistently and authentically within the whole value chain system, it leads to a higher brand equity.
Practical implications
The paper provides a guide for both academics and marketers as theoretical frameworks are examined, analysed and future recommendations are given, which are suited to be applied within the brand management principles.
Originality/value
The outcome contributes to a wider delineation regarding the future of luxury brands. The study reveals novel viewpoints concerning the integration of arts in luxury brand marketing and adds to existing literature.
Clonal transmission and horizontal gene transfer (HGT) contribute to the spread of vancomycin-resistant enterococci (VRE) in global healthcare. Our study investigated vesiduction, a HGT mechanism via ...membrane vesicles (MVs), for vanA and vanB genes that determine vancomycin resistance. We isolated MVs for VRE of different sequence types (STs) and analysed them by nanoparticle tracking analysis. Selected MV samples were subjected to DNA sequence analysis. In resistance transfer experiments, vancomycin-susceptible enterococci were exposed to MVs and bacterial supernatants of VRE. Compared to bacteria grown in lysogeny broth (MVs/LB), cultivation under vancomycin stress (MVs/VAN) resulted in increased particle concentrations of up to 139-fold (ST80). As a key finding, we could show that VRE isolates of ST80 and ST117 produced remarkably more vesicles at subinhibitory antibiotic concentrations (approx. 9.2 × 10
particles/ml for ST80 and 2.4 × 10
particles/ml for ST117) than enterococci of other STs (range between 1.8 × 10
and 5.3 × 10
particles/ml). In those MV samples, the respective resistance genes vanA and vanB were completely verifiable using sequence analysis. Nevertheless, no vancomycin resistance transfer via MVs to vancomycin-susceptible Enterococcus faecium was phenotypically detectable. However, our results outline the potential of future research on ST-specific MV properties, promising new insights into VRE mechanisms.
The receptor tyrosine kinase AXL (RTK-AXL) is implicated in therapy resistance and tumor progression in glioblastoma multiforme (GBM). Here, we investigated therapy-induced receptor modifications and ...how endogenous RTK-AXL expression and RTK-AXL inhibition contribute to therapy resistance in GBM. GBM cell lines U118MG and SF126 were exposed to temozolomide (TMZ) and radiation (RTX). Receptor modifications in response to therapy were investigated on protein and mRNA levels. TMZ-resistant and RTK-AXL overexpressing cell lines were exposed to increasing doses of TMZ and RTX, with and without RTK-AXL tyrosine kinase inhibitor (TKI). Colorimetric microtiter (MTT) assay and colony formation assay (CFA) were used to assess cell viability. Results showed that the RTK-AXL shedding product, C-terminal AXL (CT-AXL), rises in response to repeated TMZ doses and under hypoxia, acts as a surrogate marker for radio-resistance. Endogenous RTX-AXL overexpression leads to therapy resistance, whereas combination therapy of TZM and RTX with TKI R428 significantly increases therapeutic effects. This data proves the role of RTK-AXL in acquired and intrinsic therapy resistance. By demonstrating that therapy resistance may be overcome by combining AXL TKI with standard treatments, we have provided a rationale for future study designs investigating AXL TKIs in GBM.
Raw materials for animal feeding are highly deficient in Europe, which results in massive imports of soya beans from North and South America. These imports are connected with a number of ...environmental problems. Increasing the grain legume production in Europe could be a promising alternative. The impacts of introducing grain legumes into existing European crop rotations are investigated in this article. The environmental impacts are evaluated by using the SALCA (Swiss Agricultural Life Cycle Assessment) life cycle assessment method and the ecoinvent life cycle inventory database.
Four regions with potential for increasing their grain legume area were chosen for this study: Saxony-Anhalt (Germany), Barrois (France), Canton Vaud (Switzerland) and Castilla y León (Spain). In each of these regions, two crop rotations were defined: a typical cereal-based rotation without grain legumes and an alternative rotation including grain legumes. The production data were collected by the local project partners from statistics, surveys, literature, documents from extension services and using expert knowledge. The impacts of these two crop rotations were compared relative to three functional units representing different functions of agriculture: hectare per year as a measure of the land management function, € gross margin 1 for the financial function and GJ gross energy of the harvested biomass for the productive function. The following environmental impacts were analysed: demand for non-renewable energy resources, global warming potential, ozone formation, eutrophication, acidification, terrestrial and aquatic ecotoxicity as well as human toxicity. For Canton Vaud, the impacts on biodiversity and soil quality were assessed in addition.
Analysed per unit of cultivated area, the introduction of grain legumes into intensive crop rotations with a high proportion of cereals and intensive N-fertilisation leads to a reduced energy use, global warming potential, ozone formation and acidification as well as eco- and human toxicity. The main reasons for this are a reduced application of N-fertilisers (no N to the grain legume and less N to the following crop), improved possibilities for using reduced tillage techniques and greater diversification of the crop rotation, which helps to reduce problems caused by weeds and pathogens (and therefore pesticide applications). The nitrate leaching potential tends to be higher in general, but can be reduced by including catch crops or early sowing of winter grain legumes, where possible. No differences were found for the impacts of crop management on soil quality and biodiversity (studied in Canton Vaud only). In the low-input crop rotation in Spain, the introduction of peas had no favourable environmental effect, mainly because little or no N-fertiliser can be saved.
The analysis per € gross margin 1 (financial function) leads to slightly more favourable results for the grain legume crop rotations compared to the analysis per ha and year. Due to the lower yields of grain legumes compared with cereals, the advantages of grain legumes are smaller when considered per GJ gross energy of the harvested products (productive function). However, the energy efficiency is higher in crop rotations with grain legumes.
On the whole, introducing grain legumes into European crop rotations offers interesting options for reducing environmental burdens, especially in a context of depleted fossil energy resources and climate change.
Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of ...patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism.
Reliable operation of lab-on-a-chip systems depends on user-friendly, precise, and predictable fluid management tailored to particular sub-tasks of the microfluidic process protocol and their ...required sample fluids. Pressure-driven flow control, where the sample fluids are delivered to the chip from pressurized feed vessels, simplifies the fluid management even for multiple fluids. The achieved flow rates depend on the pressure settings, fluid properties, and pressure-throughput characteristics of the complete microfluidic system composed of the chip and the interconnecting tubing. The prediction of the required pressure settings for achieving given flow rates simplifies the control tasks and enables opportunities for automation. In our work, we utilize a fast-running, Kirchhoff-based microfluidic network simulation that solves the complete microfluidic system for in-line prediction of the required pressure settings within less than 200 ms. The appropriateness of and benefits from this approach are demonstrated as exemplary for creating multi-component laminar co-flow and the creation of droplets with variable composition. Image-based methods were combined with chemometric approaches for the readout and correlation of the created multi-component flow patterns with the predictions obtained from the solver.
Deficient anterior pituitary with common variable immune deficiency (DAVID) syndrome is a rare condition characterized by adrenocorticotropic hormone (ACTH) deficiency and primary ...hypogammaglobulinemia. It is due to heterozygous mutations of the nuclear factor kappa‐B subunit 2 (NFKB2) gene. Only a few isolated cases have been reported since its first description by our team. Through the international multicenter GENHYPOPIT network, we identified a new case of DAVID syndrome. We then conducted an extensive review of the DAVID syndrome cases published from 2012 to 2022. A 7‐year‐old boy was diagnosed with symptomatic hypoglycemia revealing ACTH deficiency. Laboratory tests showed asymptomatic hypogammaglobulinemia. He harbored a heterozygous point mutation in NFKB2 gene (c.2600C > T, p.Ala867Val). His management included hydrocortisone replacement treatment, and he also received subcutaneous immunoglobulins during the Covid‐19 pandemic. We analyzed 28 cases of DAVID syndrome with ACTH deficiency. ACTH deficiency was the only hormone deficiency in 79% of patients, but some patients harbored growth hormone (GH) and thyroid stimulating hormone (TSH) deficiencies. The first presenting symptoms were sinus/pulmonary infections (82%, mean age of 3 years) and alopecia (mean age of 4.7 years). ACTH deficiency was the third presenting condition (mean age at diagnosis of 8.6 years). All patients had hypogammaglobulinemia (decreased IgA and IgM levels), and 57% of patients had at least one autoimmune manifestation. Heterozygous mutations at the 3′end of the NFKB2 gene, coding for the C‐terminal domain of the protein, were identified in all cases. Better knowledge of DAVID syndrome will help clinicians make an early diagnosis to avoid life‐threatening complications.
Deficient Anterior pituitary with common Variable Immune Deficiency (DAVID) syndrome is a rare condition characterized by adrenocorticotropic hormone (ACTH) deficiency and primary hypogammaglobulinemia. It is due to heterozygous mutations of the nuclear factor kappa‐B subunit 2 (NFKB2) gene. Among28 cases published between 2012‐2022, ACTH deficiency was the only hormone deficit in 79% of patients, alopecia was present in 44% and hypogammaglobulinemia was associated with early infections and autoimmune manifestations.
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