Generalized Samuel Multiplicities of Monomial Ideals and Volumes

We describe conjecturally the generalized Samuel multiplicities c_0,...,c_{d-1} of a monomial ideal I subset K[x_1,...,x_d] in terms of its Newton polyhedron NP(I). More precisely, we conjecture that c_i equals the sum of the normalized (d-1)-volumes of pyramids over the projections of the (d-i-1)-dimensional compact faces of NP(I) along the infinite-directions of i-unbounded facets in which they are contained. For c_0 proofs are known (Guibert, Jeffries and Monta\uf1o) and for c_{d-1} a proof is given

Preliminary investigations of compatible nanolime treatments on Indiana limestone and weathered marble stone

The conservation of historic structures must be carried out through treatments that use materials which are compatible with the originals. In recent years, nanolime has been considered one of the most promising products for the consolidation of calcareous substrates due to its characteristics of high compatibility with the treated substrate and durability. The effectiveness of nanolime products has been proven for superficial consolidation treatments (e.g. plasters and wall-paintings), and research nowadays is focused on the study of the in-depth consolidation effectiveness of porous substrates. The aim of this paper is to undertake preliminary investigations of compatible nanolime treatments for Indiana limestone (US) and a weathered marble. Nanolime was synthesized by anion exchange resins and dispersed in isopropanol and ethanol. The consolidation effectiveness is assessed by studying changes in porosity, drilling resistance, surface cohesion and aesthetic appearance (colour). Results showed that nanolime yielded the highest consolidation effectiveness when treated samples were kept in high relative humidity environments (~75%RH) or regularly sprayed with carbonated water in a laboratory environment (~50%RH). These results suggest that for an on-site consolidation treatment with nanolime in dry environments, treated surfaces could be regularly sprayed with carbonated water to increase consolidation effectiveness

Standardization and clinical implementation of liquid biopsy assays - IMI's CANCER-ID

The innovative medicine initiative (IMI) project CANCER-ID (www.cancer-id.eu) is a 5 year (2014-2019) international public-private partnership of currently 40 partners from 14 countries, with the aim to evaluate technologies for Circulating Tumor Cell (CTC), circulating free tumor DNA (ctDNA), microRNA (miRNA) and exosome enrichment, isolation and analysis. At the core of CANCER-ID's activities are establishment of harmonized best practice protocols from patient sample collection, pre-analytical sample handling, sample and bioinformatics analyses down to the actionable information guiding patient selection and personalized treatment. CANCER-ID is furthermore testign and supporting development of standards for liquid biopsy as well as clinical implementation of liquid biopsy based protocols in the clinical setting. This included interaction with regulatory bodies in Europe (EMA InnovationTask Force) and the US (FDA Public-Private Partnership liaison) to support future approval of liquid biopsies in multi-centered worldwide clinical studies. During the clincial validation phase of the project, clinical-ready liquid biopsies protocols have been implemented in an observational study on the potential predictive value of monitoring treatment response to Immune Checkpoint Inhibition (ICI) in 180 NSCLC patients in the UMC Groningen, The Netherlands, as well as in two ICI-chemotherapy combination studies in triple-Negative BReast Cancer and Luminal B-type breast cancer, respectively, run by the University of Oslo, Norway (Alice NCT03164993 and ICON NCT03409198). Within both studies, blood has been collected at baseline and at follow-up visits for ctDNA and CTC analysis, including technical evaluation of CTC PD-L1 protein expression. The aim is to assess whether the allelic frequency of mutations identified by plasma NGS as a potential measure for Tumor Mutational Burden or the number of PD-L1 positive/overall CTC at different time points is indicative of treatment success. The studies aim at providing data to assess whehter clinical predictive information could be inferred from baseline number of detected mutations and PD-L1 expressing CTCs. Preliminary data of these analyses will be presented. As a follow-up activity of the IMI CANCER-ID program, the European Liquid Biopsy society (ELBS) is currently being established by Prof. Pantel at UKE Hamburg, Germany. The ELBS will be open to all interested liquid biopsy stakeholders worldwide as a platform for scientific exchange, further efforts to standardize technologies and protocols in the field as well as for the initiation of the new basic and clinical research projects with the aim to make liquid biopsies and integral part of clinical studies and patient care. This work is supported by IMI JU & EFPIA (grant no. 115749, CANCER-ID). Samples from patients and healthy volunteers, respectively, were collected under signed informed consent

Molecular profiling of single circulating tumor cells with diagnostic intention

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance

Parvovirus B19 DNA CpG Dinucleotide Methylation and Epigenetic Regulation of Viral Expression

CpG DNA methylation is one of the main epigenetic modifications playing a role in the control of gene expression. For DNA viruses whose genome has the ability to integrate in the host genome or to maintain as a latent episome, a correlation has been found between the extent of DNA methylation and viral quiescence. No information is available for Parvovirus B19, a human pathogenic virus, which is capable of both lytic and persistent infections. Within Parvovirus B19 genome, the inverted terminal regions display all the characteristic signatures of a genomic CpG island; therefore we hypothesised a role of CpG dinucleotide methylation in the regulation of viral genome expression