Radicals in carbonaceous residue deposited on mordenite from methanol

It is shown that control of the degree of coking can lead to the observation of hyperfine structures in the carbonaceous residues deposited from methanol over mordenite (H-MOR) at temperatures relevant to the conversion of methanol to hydrocarbons. EPR measurements of the catalyst samples at various times on stream have been recorded, with a rich hyperfine splitting pattern observed in the early stages of the reaction. Interpretation of the EPR data with the aid of density functional theoretical calculations has afforded the first definitive assignment of the radical cations formed in high temperature coke. The results detail a shortlist of six species: 2,3/2,6/2,7-dimethylnaphthalenium, 2,3,6-trimethylnaphthalenium, 2,3,6,7-tetramethylnaphthalenium, and anthracenium radical cations whose proton hyperfine splitting profiles match the experimental spectra; 2,3,6,7-tetramethylnaphthalenium showed the best agreement. The observation of these particular isomers of polymethylnaphthalene suggest the formation of more highly branched polyaromatic species is less likely within the confines of the H-MOR 12-membered ring channel. These radicals formed when the catalyst is active may constitute key intermediates in the conversion of methanol to light olefins

An investigation of the nature and reactivity of the carbonaceous species deposited on mordenite by reaction with methanol

An investigation of the nature of the carbonaceous species deposited upon mordenite by reaction with methanol has been undertaken. The nature of the species has been shown to be a strong function of both temperature and time on stream. Upon reaction at 300 degrees C a range of alkyl and aromatic species, consistent with the development of an active hydrocarbon pool, are evident and time on stream studies have shown that these are developed within 5 min. Upon reaction at 500 degrees C, a narrower range of hydrogen deficient aromatic species is evident. Thermal volatilisation analysis (TVA), not previously applied to the study of coked zeolites, is shown to be complementary to the more commonly applied C analysis, C-13 MAS NMR and TGA techniques

Exacerbation of visual hallucinations in Charles Bonnet syndrome due to the social implications of COVID-19

Objective: Charles Bonnet syndrome (CBS) occurs secondary to sight loss, characterised by spontaneous visual hallucinations. Symptom manifestation can be influenced by social isolation. This research aims to evaluate the effect of the COVID-19 pandemic lockdown on patients with CBS. / Methods and analysis: A prospective cross-sectional survey of 45 individuals with active CBS. Open and closed ended questions were used to measure patient-reported features of hallucinatory experiences during the COVID-19 lockdown and perceived episode triggers. Analysis comprised of descriptive statistics, analysis of variance and associations, supplemented with qualitative descriptions. / Results: The survey was operational for 31 days during the COVID-19 pandemic (June–July 2020). The mean (±SD) age of respondents was 69.3 (±18) years and the majority (42.2%) had macular disease. Loneliness during the lockdown was associated with changes in the nature of visual hallucinations (p=0.04). Individuals experiencing greater loneliness were, on average, older than those with no changes to their feelings of loneliness (mean age 73.3±17 vs 60.2±19 years; p=0.03). Despite experiencing greater feelings of loneliness (67%), most individuals (60%) had not accessed support services for this reason. / Conclusions: Around half of respondents in this survey experienced exacerbation of visual hallucinations during the COVID-19 pandemic, which may partly be explained by loneliness and/or environmental triggers. We provide suggestions to promote effective patient self-management of symptoms

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy

De novo pathway-based biomarker identification

Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent datasets. Attempts to mitigate these drawbacks have led to the development of network-based approaches that integrate pathway information to produce meta-gene (MG) features. Also, MG approaches have only dealt with the two-class problem of good versus poor outcome prediction. Stratifying patients based on their molecular subtypes can provide a detailed view of the disease and lead to more personalized therapies. We propose and discuss a novel MG approach based on de novo pathways, which for the first time have been used as features in a multi-class setting to predict cancer subtypes. Comprehensive evaluation in a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) revealed that MGs are considerably more stable than SG models, while also providing valuable insight into the cancer hallmarks that drive them. In addition, when tested on an independent benchmark non-TCGA dataset, MG features consistently outperformed SG models. We provide an easy-touse web service at http:// pathclass. compbio. sdu. dk where users can upload their own gene expression datasets from breast cancer studies and obtain the subtype predictions from all the classifiers

Vergelijking van 1F-uitsluitingen van Syrische asielzoekers in Nederland en België

Vermoedens van betrokkenheid bij oorlogsmisdrijven en andere ernstige misdrijven kunnen leiden tot uitsluiting van asielbescherming op basis van artikel 1F Vluchtelingenverdrag. Hoe wordt dit artikel toegepast bij Syrische asielzoekers, sinds het begin van de Syrische burgeroorlog? Maarten Bolhuis, Tara Ditzel en Joris van Wijk bespreken de overeenkomsten en verschillen tussen Syrische 1F-zaken in Nederland en België. De verschillende standaarden van Nederlandse en Belgische rechters komen aan de orde, evenals verschillen in interpretatie van pendanten van schulduitsluitingscriteria, zoals overmacht en dwang. Daarbij blijkt dat de Nederlandse rechter artikel 1F ruimer toepast dan de Belgische, met name in verband met indirecte betrokkenheid bij 1F-misdrijven en de interpretatie van die pendanten

Global MicroRNA Expression Profiling of High-Risk ER+ Breast Cancers from Patients Receiving Adjuvant Tamoxifen Mono-Therapy: A DBCG Study

PURPOSE: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence. EXPERIMENTAL DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables. RESULTS: The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics. CONCLUSIONS: Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics

Visualization of Myelin Basic Protein (Mbp) T Cell Epitopes in Multiple Sclerosis Lesions Using a Monoclonal Antibody Specific for the Human Histocompatibility Leukocyte Antigen (Hla)-Dr2–Mbp 85–99 Complex

Susceptibility to multiple sclerosis (MS) is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 haplotype, suggesting that major histocompatibility complex class II–restricted presentation of central nervous system–derived antigens is important in the disease process. Antibodies specific for defined HLA-DR2–peptide complexes may therefore be valuable tools for studying antigen presentation in MS. We have used phage display technology to select HLA-DR2–peptide-specific antibodies from HLA-DR2–transgenic mice immunized with HLA-DR2 molecules complexed with an immunodominant myelin basic protein (MBP) peptide (residues 85–99). Detailed characterization of one clone (MK16) demonstrated that both DR2 and the MBP peptide were required for recognition. Furthermore, MK16 labeled intra- and extracellular HLA-DR2–MBP peptide complexes when antigen-presenting cells (APCs) were pulsed with recombinant MBP. In addition, MK16 inhibited interleukin 2 secretion by two transfectants that expressed human MBP–specific T cell receptors. Analysis of the structural requirement for MK16 binding demonstrated that the two major HLA-DR2 anchor residues of MBP 85–99 and the COOH-terminal part of the peptide, in particular residues Val-96, Pro-98, and Arg-99, were important for binding. Based on these results, the antibody was used to determine if the HLA-DR2–MBP peptide complex is presented in MS lesions. The antibody stained APCs in MS lesions, in particular microglia/macrophages but also in some cases hypertrophic astrocytes. Staining of APCs was only observed in MS cases with the HLA-DR2 haplotype but not in cases that carried other haplotypes. These results demonstrate that HLA-DR2 molecules in MS lesions present a myelin-derived self-peptide and suggest that microglia/macrophages rather than astrocytes are the predominant APCs in these lesions

On the two first excited K=0 bands in U-238 and Pu-240

EO-enhanced spectra of conversion electrons taken after (alpha,alpha) and (alpha,2n) reactions and after projectile Coulomb excitation improve our knowledge about first and second excited bands in U-238 and Pu-240 built on O-2(+) and O-3(+) states which lie anomalously close together. The two bands are of different structure.</p