Nano-agglomerated capillary polymer monoliths for applications in micro-catalysis and separation science

In this thesis, novel approaches to the preparation and characterisation of nanoagglomerated polymer monoliths are described. Polymer monoliths in various formats were prepared by availing of in-situ photopolymerisation techniques, with the modification of surface chemistry achieved via grafting selected amine-reactive monomers, facilitating the subsequent attachment of metal nano-materials. Traditional destructive characterisation methods such as field emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy provided the qualitative confirmation of the presence of the nano materials. A very dense coverage of bimetallic Pd/Pt nano-flowers was achieved upon the surface of such polymer monoliths. The macro-porous structure of the monoliths and the high coverage of nano-particles facilitated catalytic applications, such as the oxidation of NADH to NAD+, in flow-through configuration. The rate of reaction was found to be dependant on the initial NADH concentration. Other polymer monoliths were functionalised with gold nano-particle (AuNPs) of various sizes in order to evaluate the effects of nano-particle size on catalytic efficiency. The catalytic properties of the immobilised AuNPs were retained following immobilisation, as demonstrated by the reduction of ferrocyanide from Fe(ІІІ) to Fe(ІІ). A 57% conversion rate was obtained when the reaction was performed on monolithic surfaces which had been functionalised with 16 nm AuNPs. Higher reaction yields (95 %) were obtained when 7 nm AuNPs were used. Non-invasive and non-destructive scanning capacitively coupled contactless conductivity detection (sC4D) was applied to monitor the temporal stability of surfactant and polyelectrolyte coatings in capillary columns which would traditionally be applied in capillary electrophoresis. The benefits of this technique were further illustrated by confirming the presence of AuNPs and PAA-grafted silica nano-particles (SiNPs) on previously aminated or quaternary ammonium functionalised monoliths. The movement of the nanoparticle’s plug was monitored at mm increments as it progressed along the column. Finally, an evaluation of the chromatographic properties of nano-agglomerated stationary phases was performed. Reversed-phase applications of AuNP functionalised monoliths were demonstrated upon further modification of the nanoparticles with alkylthiol and alkylamine chains. However, poor chromatographic performance was observed with a test mixture of alkylbenzenes due to the limited hydrophobicity of the stationary phase. Ion-exchange applications were also possible upon modification of the immobilised AuNPs with sulphonate groups, which was demonstrated by the retention of Ca2+ ions. PAA-grafted SiNPs were immobilised on the surface of a quaternary ammonium-functionalised polymer monolith and the anion-exchange properties of the stationary phase demonstrated by separating a mixture of Cl- and H2PO4 -. The immobilisation of negatively charged PAA-grafted SiNPs however, lead to the formation of a cation-exchange stationary phase as confirmed by the retention of Ca2+ and Mg2+

Development and characterisation of switchable polyaniline-functionalised flow-through capillary monoliths

Polymer monoliths were prepared in capillary format (250 mm i.d.) and used as solid supports for the immobilisation of the conducting polymer polyaniline (PANI). The immobilisation of PANI was confirmed on the large macro-porous structure of a polystyrene–divinylbenzene (PS-co-DVB) monolith. The surface coverage of polyaniline was characterised by field emission scanning electron microscopy (FESEM) and by capacitively coupled contactless conductivity detection (C4D), which was operated in scanning mode to non-invasively visualise the axial distribution of the immobilised PANI and to provide information on its doping state. To further demonstrate the successful functionalisation of the monoliths, the PANI-functionalised monoliths were demonstrated as switchable, weak anion-exchange stationary phases as confirmed by studying the retention of iodide using a perchlorate eluent

The fine structure line deficit in S 140

We try to understand the gas heating and cooling in the S 140 star forming region by spatially and spectrally resolving the distribution of the main cooling lines with GREAT/SOFIA. We mapped the fine structure lines of [OI] (63 {\mu}m) and [CII] (158 {\mu}m) and the rotational transitions of CO 13-12 and 16-15 with GREAT/SOFIA and analyzed the spatial and velocity structure to assign the emission to individual heating sources. We measure the optical depth of the [CII] line and perform radiative transfer computations for all observed transitions. By comparing the line intensities with the far-infrared continuum we can assess the total cooling budget and measure the gas heating efficiency. The main emission of fine structure lines in S 140 stems from a 8.3'' region close to the infrared source IRS 2 that is not prominent at any other wavelength. It can be explained by a photon-dominated region (PDR) structure around the embedded cluster if we assume that the [OI] line intensity is reduced by a factor seven due to self-absorption. The external cloud interface forms a second PDR at an inclination of 80-85 degrees illuminated by an UV field of 60 times the standard interstellar radiation field. The main radiation source in the cloud, IRS 1, is not prominent at all in the fine structure lines. We measure line-to-continuum cooling ratios below 10^(-4), i.e. values lower than in any other Galactic source, rather matching the far-IR line deficit seen in ULIRGs. In particular the low intensity of the [CII] line can only be modeled by an extreme excitation gradient in the gas around IRS 1. We found no explanation why IRS 1 shows no associated fine-structure line peak, while IRS 2 does. The inner part of S 140 mimics the far-IR line deficit in ULIRGs thereby providing a template that may lead to a future model.Comment: Accepted for publication in Astronomy & Astrophysic

A High-Throughput Candida albicans Two-Hybrid System

We thank Nico Vangoethem for help with preparation of the figures and Ilse Palmans, Tom Adriany, and Selien Schots for technical assistance. Financial support was obtained from the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (IAP P7/28) and by the KU Leuven Research Council (C14/17/063). C.D. acknowledges support from the French Government’s Investissement d’Avenir program (Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases, ANR-10-LABX-62-IBEID). C.A.M. and C.D. acknowledge support from the Wellcome Trust (088858/Z/09/Z). C.A.M. acknowledges support from the MRC Centre for Medical Mycology (MR/N006364/1) and the University of Aberdeen.Peer reviewedPublisher PD

Clinical Characteristics and Outcomes of Patients With Cutibacterium acnes Endocarditis

Importance: It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement. Objective: To assess the clinical characteristics and outcomes of patients with C acnes endocarditis. Design, Setting, and Participants: A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022. Main Outcomes and Measures: Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates. Results: A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%]). Conclusions and Relevance: This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence.</p

Short-termed changes in quantitative ultrasound estimated bone density among young men in an 18-weeks follow-up during their basic training for the Swiss Armed Forces

Background Quantitative Ultrasound (QUS) methods have been widely used to assess estimated bone density. This study aimed to assess changes in estimated bone density in association with changes in body composition, physical activity, and anthropometry. Methods We examined changes in anthropometry, body composition, and physical activity associated with changes in estimated bone mineral density (measured using quantitative ultrasound with a heel ultrasound device indicating broadband ultrasound attenuation BUA and speed of sound SOS) in a follow-up sample of n = 73 young men at the beginning and again 18 weeks later at the end of basic military training. Results At the end of the basic training, the subjects were on average significantly heavier (+1.0%), slightly taller (+0.5%) and had a higher fat mass (+6.6%) and grip strength (+8.6%). A significant decrease in mean physical activity (−49.5%) and mean estimated bone density calculated with BUA (−7.5%) was observed in the paired t-test. The results of the multivariable linear regressions (backward selection) show that changes in skeletal muscle mass (delta = 2nd measurement minus 1st measurement) have negative and body weight (delta) have positive association with the speed of sound SOS (delta), while fat mass (delta) and physical activity (delta) had the strongest negative associations with estimated bone mineral density (delta). In particular, we found a negative association between fat mass (delta) and estimated bone mineral density (delta, estimated with BUA). Conclusion Our study suggests that estimated bone density from the calcaneus can change within a few months even in young and mostly healthy individuals, depending upon physical activity levels and other co-factors. Further studies including other troop types as control groups as well as on women should follow in order to investigate this public health relevant topic in more depth. To what extent the estimated bone density measurement with quantitative ultrasound is clinically relevant needs to be investigated in further studies

The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, lacking effective therapy. Many TNBCs show remarkable response to carboplatin-based chemotherapy, but often develop resistance over time. With increasing use of carboplatin in the clinic, there is a pressing need to identify vulnerabilities of carboplatin-resistant tumors. In this study, we generated carboplatin-resistant TNBC MDA-MB-468 cell line and patient derived TNBC xenograft models. Mass spectrometry-based proteome profiling demonstrated that carboplatin resistance in TNBC is linked to drastic metabolism rewiring and upregulation of anti-oxidative response that supports cell replication by maintaining low levels of DNA damage in the presence of carboplatin. Carboplatin-resistant cells also exhibited dysregulation of the mitotic checkpoint. A kinome shRNA screen revealed that carboplatin-resistant cells are vulnerable to the depletion of the mitotic checkpoint regulators, whereas the checkpoint kinases CHEK1 and WEE1 are indispensable for the survival of carboplatin-resistant cells in the presence of carboplatin. We confirmed that pharmacological inhibition of CHEK1 by prexasertib in the presence of carboplatin is well tolerated by mice and suppresses the growth of carboplatin-resistant TNBC xenografts. Thus, abrogation of the mitotic checkpoint by CHEK1 inhibition re-sensitizes carboplatin-resistant TNBCs to carboplatin and represents a potential strategy for the treatment of carboplatin-resistant TNBCs