Smart strategies for the transition in coal intensive regions

The TRACER project supports a number of coal-intensive regions around Europe to design (or re-design) their Research and Innovation (R&I) strategies in order to facilitate their transition towards a sustainable energy system. The TRACER consortium consists of different target regions: South East Bulgaria, North West Bohemia - Czech Republic, Lusatian Lignite District - Germany, Western Macedonia - Greece, Upper Silesian Coalfield - Poland, West Region, Jiu Valley - Romania, Wales – UK, Kolubara - Serbia, Donetsk - Ukraine. Core activities of TRACER include the implementation of an EDP (Entrepreneurial Discovery Process) to mobilise a wide range of stakeholders in each target region to develop an appropriate governance structure and to bring regional stakeholders together to discuss and agree on a shared vision and priorities for coal transition. R&I strategies, industrial roadmaps and decision support tools will be developed jointly with key stakeholders of the TRACER target regions. Further TRACER activities include the identification and analysis of best practice examples of successful and ambitious transition processes in coal intensive regions, a detailed assessment of social, environmental and technological challenges, the elaboration of guidelines on how to mobilise investment as well as dedicated activities to stimulate R&I cooperation among coal intensive regions in Europe and beyond

Intersection of Immune and Oncometabolic Pathways Drives Cancer Hyperprogression During Immunotherapy

Immune checkpoint blockade (ICB) can produce durable responses against cancer. We and others have found that a subset of patients experiences paradoxical rapid cancer progression during immunotherapy. It is poorly understood how tumors can accelerate their progression during ICB. In some preclinical models, ICB causes hyperprogressive disease (HPD). While immune exclusion drives resistance to ICB, counterintuitively, patients with HPD and complete response (CR) following ICB manifest comparable levels of tumor-infiltrating CD

On-line coloring of IsI_s-free graphs

International audienceAn on-line vertex coloring algorithm receives vertices of a graph in some externally determined order. Each new vertex is presented together with a set of the edges connecting it to the previously presented vertices. As a vertex is presented, the algorithm assigns it a color which cannot be changed afterwards. The on-line coloring problem was addressed for many different classes of graphs defined in terms of forbidden structures. We analyze the class of $I_s$-free graphs, i.e., graphs in which the maximal size of an independent set is at most $s-1$. An old Szemerédi's result implies that for each on-line algorithm A there exists an on-line presentation of an $I_s$-free graph $G$ forcing A to use at least $\frac{s}{2}χ ^{(G)}$ colors. We prove that any greedy algorithm uses at most $\frac{s}{2}χ^{(G)}$ colors for any on-line presentation of any $I_s$-free graph $G$. Since the class of co-planar graphs is a subclass of $I_5$-free graphs all greedy algorithms use at most $\frac{5}{2}χ (G)$ colors for co-planar $G$'s. We prove that, even in a smaller class, this is an almost tight bound

On-line coloring of IsI_s-free graphs

An on-line vertex coloring algorithm receives vertices of a graph in some externally determined order. Each new vertex is presented together with a set of the edges connecting it to the previously presented vertices. As a vertex is presented, the algorithm assigns it a color which cannot be changed afterwards. The on-line coloring problem was addressed for many different classes of graphs defined in terms of forbidden structures. We analyze the class of $I_s$-free graphs, i.e., graphs in which the maximal size of an independent set is at most $s-1$. An old Szemerédi's result implies that for each on-line algorithm A there exists an on-line presentation of an $I_s$-free graph $G$ forcing A to use at least $\frac{s}{2}χ ^{(G)}$ colors. We prove that any greedy algorithm uses at most $\frac{s}{2}χ^{(G)}$ colors for any on-line presentation of any $I_s$-free graph $G$. Since the class of co-planar graphs is a subclass of $I_5$-free graphs all greedy algorithms use at most $\frac{5}{2}χ (G)$ colors for co-planar $G$'s. We prove that, even in a smaller class, this is an almost tight bound

Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients

<p>Immune checkpoint blockade (ICB) therapies have emerged as a promising avenue for the treatment of various cancers. Despite their success, the efficacy of these treatments is variable across patients and cancer types. Numerous single-cell RNA-sequencing (scRNA-seq) studies have been conducted to unravel cell-specific responses to ICB treatment. However, these studies are limited in their sample sizes and require advanced coding skills for exploration. Here, we have compiled eight scRNA-seq datasets from nine cancer types, encompassing 174 patients, and 90,270 cancer cells. This compilation forms a unique resource tailored for investigating how cancer cells respond to ICB treatment across cancer types. We meticulously curated, quality-checked, pre-processed, and analyzed the data, ensuring easy access for researchers. Moreover, we designed a user-friendly interface for seamless exploration. By sharing the code and data for creating these interfaces, we aim to assist fellow researchers. These resources offer valuable support to those interested in leveraging and exploring single-cell datasets across diverse cancer types, facilitating a comprehensive understanding of ICB responses.</p&gt

Reliability and Utility of Various Methods for Evaluation of Bone Union after Anterior Cervical Discectomy and Fusion

Most surgical procedures performed on account of degenerative disease of the cervical spine involve a discectomy and interbody fixation. Bone fusion at the implant placement site is evaluated post-operatively. It is agreed that computed tomography is the best modality for assessing bone union. We evaluated the results obtained with various methods based solely on conventional radiographs in the same group of patients and compared them with results obtained using a method that is a combination of CT and conventional radiography, which we considered the most precise and a reference method. We operated on a total of 170 disc spaces in a group of 104 patients. Fusion was evaluated at 12 months after surgery with five different and popular classifications based on conventional radiographs and then compared with the reference method. Statistical analyses of test accuracy produced the following classification of fusion assessment methods with regard to the degree of consistency with the reference method, in descending order: (1) bone bridging is visible on the anterior and/or posterior edge of the operated disc space on a lateral radiograph; (2) change in the value of Cobb’s angle for a motion segment on flexion vs. extension radiographs (threshold for fusion vs. pseudoarthrosis is 2°); (3) change in the interspinous distance between process tips on flexion vs. extension radiographs (threshold of 2 mm); (4) change in the value of Cobb’s angle of a motion segment (threshold of 4°); (5) change in the interspinous distance between process bases on flexion vs. extension radiographs (threshold of 2 mm). When bone union is evaluated on the basis on radiographs, without CT evidence, we suggest using the “bone bridging” criterion as the most reliable commonly used approach to assessing bone union

Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors

Summary: Disruption of antigen presentation via loss of major histocompatibility complex (MHC) expression is a strategy whereby cancer cells escape immune surveillance and develop resistance to immunotherapy. Here, we develop the personalized genomics algorithm Hapster and accurately call somatic mutations within the MHC genes of 10,001 primary and 2,199 metastatic tumors, creating a catalog of 1,663 non-synonymous mutations that provide key insights into MHC mutagenesis. We find that MHC class I genes are among the most frequently mutated genes in both primary and metastatic tumors, while MHC class II mutations are more restricted. Recurrent deleterious mutations are found within haplotype- and cancer-type-specific hotspots associated with distinct mutational processes. Functional classification of MHC residues reveals significant positive selection for mutations disruptive to the B2M, peptide, and T cell binding interfaces, as well as to MHC chaperones