Quantitative determination of ochratoxin A in wine after the clarification and filtration

Through the use of the analytical method known as HPLC-FD and previously used the method for extraction of ochratoxin A by immunoaffinity columns, we have analyzed the possible effect of the clarification and filtration process on 54 samples of 2013 newly fermented wine, which have finished alcoholic fermentation process and racking, without knowing in advance whether there and how is the amount of OTA in wine. The racking of the wine before clarification and filtration followed by adequate clarification and filtration process during winemaking seems to be crucial in the reduction or complete elimination of the analyzed mycotoxin (OTA).The results of all analyzed samples have been below the limit allowed by the EU for ochratoxin A i.e. 2 ng/ml, and as such does not represent a risk to human health

Comparing Detection Capabilities of AntiVirus Products: An Empirical Study with Different Versions of Products from the Same Vendors

In this paper we report results of an empirical analysis of the detection capabilities of 9 AntiVirus (AV) products when they were subjected to 3605 malware samples collected on an experimental network over a period of 31 days in NovemberDecember 2013. We compared the detection capabilities of the version of the AV products that the vendors make available for free in VirusTotal versus the full capability products that they make available via their own website. The analysis has been done using externally observable properties of the AV products: namely whether they detect a given malware. The paper reports extensive analysis of the results. A surprising finding of our study was that only one of the vendors had a full capability version which detected all the malware that their VirusTotal version could detect

Feasibility of detecting atrophy relevant for disability and cognition in multiple sclerosis using 3D-FLAIR

BACKGROUND AND OBJECTIVES: Disability and cognitive impairment are known to be related to brain atrophy in multiple sclerosis (MS), but 3D-T1 imaging required for brain volumetrics is often unavailable in clinical protocols, unlike 3D-FLAIR. Here our aim was to investigate whether brain volumes derived from 3D-FLAIR images result in similar associations with disability and cognition in MS as do those derived from 3D-T1 images. METHODS: 3T-MRI scans of 329 MS patients and 76 healthy controls were included in this cross-sectional study. Brain volumes were derived using FreeSurfer on 3D-T1 and compared with brain volumes derived with SynthSeg and SAMSEG on 3D-FLAIR. Relative agreement was evaluated by calculating the intraclass correlation coefficient (ICC) of the 3D-T1 and 3D-FLAIR volumes. Consistency of relations with disability and average cognition was assessed using linear regression, while correcting for age and sex. The findings were corroborated in an independent validation cohort of 125 MS patients. RESULTS: The ICC between volume measured with FreeSurfer and those measured on 3D-FLAIR for brain, ventricle, cortex, total deep gray matter and thalamus was above 0.74 for SAMSEG and above 0.91 for SynthSeg. Worse disability and lower average cognition were similarly associated with brain (adj. R2 = 0.24-0.27, p < 0.01; adj. R2 = 0.26-0.29, p < 0.001) ventricle (adj. R2 = 0.27-0.28, p < 0.001; adj. R2 = 0.19-0.20, p < 0.001) and deep gray matter volumes (adj. R2 = 0.24-0.28, p < 0.001; adj. R2 = 0.27-0.28, p < 0.001) determined with all methods, except for cortical volumes derived from 3D-FLAIR. DISCUSSION: In this cross-sectional study, brain volumes derived from 3D-FLAIR and 3D-T1 show similar relationships to disability and cognitive dysfunction in MS, highlighting the potential of these techniques in clinical datasets

How Can Tufa Deposits Contribute to the Geotourism Offer? The Outcomes from the First UNESCO Global Geopark in Serbia

The study focuses on the present state and the assessments of geotourism development of the two most representative tufa deposits in the Djerdap National Park—the first UNESCO Global Geopark in Serbia. The findings were designated through implementing the freshly upgraded methodology—M-GAM-1-2 based on an early modified geosites assessment model (M-GAM). To overcome the limitations of the previous model, the authors implemented additional enhancements and involved members of the local community (residents and authorities) in the study to comprehensively evaluate the observed sites. The outcomes revealed that the attitudes of all stakeholders should be taken into consideration in order to develop geotourism properly, additionally attract visitors, and preserve tufa deposits for future generations of locals and visitors. Moreover, geotourism at the observed sites can be one of the vital activities of the population, as well as a type of compensation for various limitations in the development, which are imposed by the regimes of natural and cultural heritage protection within the recently established UNESCO Global Geopark

PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-γ-induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations

Histone H3.3 mutations drive pediatric glioblastoma through upregulation of MYCN

Children and young adults with glioblastoma (GBM) have a median survival rate of only 12 to 15 months, and these GBMs are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A, occurring either at or close to key residues marked by methylation for regulation of transcription-K27 and G34. Here, we show that the cerebral hemisphere-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem-cell maintenance, cell-fate decisions, and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene that is causative of GBMs when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population through inhibiting kinases responsible for stabilization of the protein.The authors acknowledge NHS funding to the National Institute for Health Research Biomedical Research Centre.This work is supported by Cancer Research UK, the Wellcome Trust, the Samantha Dickson Brain Tumour Trust, and The Stravros Niarchos Foundation

Integrative molecular and functional profiling of ERBB2-amplified breast cancers identifies new genetic dependencies.

Overexpression of the receptor tyrosine kinase ERBB2 (also known as HER2) occurs in around 15% of breast cancers and is driven by amplification of the ERBB2 gene. ERBB2 amplification is a marker of poor prognosis, and although anti-ERBB2-targeted therapies have shown significant clinical benefit, de novo and acquired resistance remains an important problem. Genomic profiling has demonstrated that ERBB2+ve breast cancers are distinguished from ER+ve and 'triple-negative' breast cancers by harbouring not only the ERBB2 amplification on 17q12, but also a number of co-amplified genes on 17q12 and amplification events on other chromosomes. Some of these genes may have important roles in influencing clinical outcome, and could represent genetic dependencies in ERBB2+ve cancers and therefore potential therapeutic targets. Here, we describe an integrated genomic, gene expression and functional analysis to determine whether the genes present within amplicons are critical for the survival of ERBB2+ve breast tumour cells. We show that only a fraction of the ERBB2-amplified breast tumour lines are truly addicted to the ERBB2 oncogene at the mRNA level and display a heterogeneous set of additional genetic dependencies. These include an addiction to the transcription factor gene TFAP2C when it is amplified and overexpressed, suggesting that TFAP2C represents a genetic dependency in some ERBB2+ve breast cancer cell

A Case Study on the Danube Limes in Serbia: Valorisation and Cartographic Analyses of Selected Tourism Products

Cultural assets in the area of the Danube Limes in Serbia are an integral part of the world heritage “Roman Empire Borders”. The research presented in this paper includes the tourist and cartographic visualization of 19 Roman sites in the Danube Limes region of Golubac–Radujevac, to determine the real possibilities of tourism development in this area. The historical and cultural heritage of this area is among the most attractive tourist destinations in Serbia, Djerdap National Park and Djerdap Geopark. Despite its diverse cultural and historical values and the specific and unique natural environment, this area is not sufficiently used for tourism. The research included the evaluation of localities, which may serve as the basis to establish which activities should be undertaken in order to plan, use, preserve, and protect such important cultural assets, under the principles of sustainable tourism development. Information based on spatially referenced data in the research process requires cartographic support, in order to understand the geospatial relations of the site significance. Cartographic visualization enabled efficiently systematized data organization, spatial identification, presentation, and the use of complex information from the mapped area in the data analysis in this paper