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Conserved, ultraconserved and other classes of constrained non-coding elements (referred as CNEs) represent one of the mysteries of current comparative genomics.These elements are defined using various degrees of sequence similarity between organisms and several thresholds of minimal length and are often marked by extreme conservation that frequently exceeds the one observed for protein-coding sequences.We here explore the distribution of different classes of CNEs in entire chromosomes, in the human genome. We employ two complementary methodologies, the scaling of block entropy and box-counting, with the aim to assess fractal characteristics of different CNE datasets. Both approaches converge to the conclusion that well-developed fractality is characteristic of elements that are either marked by extreme conservation between two or more organisms or are of ancient origin, i.e. conserved between distant organisms across evolution. Given that CNEs are often clustered around genes, especially those that regulate developmental processes, we verify by appropriate gene masking that fractal-like patterns emerge irrespectively of whether elements found in proximity or inside genes are excluded or not. An evolutionary scenario is proposed, involving genomic events, that might account for fractal distribution of CNEs in the human genome as indicated through numerical simulations.

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In this research, we present the results from the comparison of temperature measurements that were made over different external points of public spaces in the old town of Xanthi. The area is located in northern Greece and is a protected settlement. All the points where the measurements were made are paved with dark gray granite blocks. This material has always been used to pave the open public spaces of the old town. Through the comparison of temperature measurements, it was found that the older paving materials develop higher temperatures compared to similar, but newer materials. Thus, it was concluded that the age of the paving materials affects the comfort of the users of the open public spaces. To test this, measurements were made during two months in spring and summer. During this period, the temperatures are higher and thus affect the users of the outdoor areas more; this results in a more useful comparison of the coating materials.

BackgroundHead and neck squamous cell carcinoma (HNSCC) is composed of a heterogeneous group of tumors arising trough environmental carcinogens or infection by human papillomavirus (HPV). Treatment interventions such as immunotherapy and targeted therapy have shown clinical benefit in HNSCC patients. Despite these encouraging results, resistance to treatment is still observed in the majority of patients. Additionally, clinical effectiveness of treatment options has also been shown to be associated with HPV status. Here we investigate the tumoral and peripheral landscape of HPV(-) vs. HPV(+) head and neck cancers to identify features able to expand treatment options for patients with Viral- and Carcinogen-Driven Head and Neck Cancer.MethodsBiopsies and serum samples derived from 502 primary and metastatic HNSCC patients were leveraged for genomic, proteomic and immunochemistry evaluations. Tumor biopsies from HNSCC patients commercially obtained (n=143) or derived from patients enrolled in CP1108 trial (n=19, NCT01693562) were profiled by gene expression. Primary tumor biopsies (N=198) from HNSCC have been assessed by Whole Exome Sequence (WES). Expression of immune markers including CD8, NKp46 was evaluated by immunohistochemistry (IHC) on 186 and 214 tumors biopsies, respectively. The expression of 80 immune related soluble factors was evaluated in serum derived from n=285 patients of HNSCC enrolled in EAGLE (NCT02369874), a randomized, open-label, study assessing Durvalumab and Tremelimumab vs. Standard of Care (SoC). Statistical comparison between HPV(+) vs. HPV (-) samples were conducted using R software.ResultsPatients with HPV(-) vs. HPV(+) HNSCC were characterized by worse prognosis. Increased levels of immunosuppressive factors including VEGF (p=0.01), IL-8 (p=0.02), IL6 (p=0.07) and macrophages chemo attractive factor CCL4 (p=0.07) was observed in the serum of HPV(-) vs HPV(+) HNSCC patients. In the tumor microenvironment, higher mRNA expression of immune signatures associated with MDSC, Cancer Associated Fibroblast (CAF), and Metalloproteinase (MMP) was observed in HPV(-) vs. HPV (+) HNSCC patients. In contrast, HNSCC HPV(+) patients were characterized by increased mRNA expression of DC signatures and IFNg related genes (i.e. CXCL9). No differential infiltration of T and NK cells (CD8+ and NKp46+) were found in HPV (-) vs. HPV(+) patients. Enrichments of mutations in EGFR, and DNA repair genes (PMS1, POLK, ATM) was observed in HPV(+) patients. On the contrary, enrichments of mutations in TP53 was observed in HPV(-) patients.ConclusionsDeep evaluation of tumoral and peripheral landscape of viral- versus carcinogen-driven HNSCC might help understanding differential outcome of treatments regimens in HPV(+) vs HPV (-) HNSCC thus leading to novel therapeutic interventions.Trial RegistrationNCT01693562,NCT02369874Ethics ApprovalThe study was approved by Astrazeneca.ConsentPatients provided written consent to perform evalutions here described.