Entropy and Long range correlations in literary English

Recently long range correlations were detected in nucleotide sequences and in human writings by several authors. We undertake here a systematic investigation of two books, Moby Dick by H. Melville and Grimm's tales, with respect to the existence of long range correlations. The analysis is based on the calculation of entropy like quantities as the mutual information for pairs of letters and the entropy, the mean uncertainty, per letter. We further estimate the number of different subwords of a given length $n$. Filtering out the contributions due to the effects of the finite length of the texts, we find correlations ranging to a few hundred letters. Scaling laws for the mutual information (decay with a power law), for the entropy per letter (decay with the inverse square root of $n$) and for the word numbers (stretched exponential growth with $n$ and with a power law of the text length) were found.Comment: 8 page

Improved understanding of dynamic water and mass budgets of high‐alpine karst systems obtained from studying a well‐defined catchment area

Large areas of Europe, especially in the Alps, are covered by carbonate rocks and in many alpine regions, karst springs are important sources for drinking water supply. Because of their high variability and heterogeneity, the understanding of the hydrogeological functioning of karst aquifers is of particular importance for their protection and utilisation. Climate change and heavy rainfall events are major challenges in managing alpine karst aquifers which possess an enormous potential for future drinking water supply. In this study, we present research from a high‐alpine karst system in the UNESCO Biosphere Reserve Großes Walsertal in Austria, which has a clearly defined catchment and is drained by only one spring system. Results show that (a) the investigated system is a highly dynamic karst aquifer with distinct reactions to rainfall events in discharge and electrical conductivity; (b) the estimated transient atmospheric CO2 sink is about 270 t/a; (c) the calculated carbonate rock denudation rate is between 23 and 47 mm/1000a and (d) the rainfall‐discharge behaviour and the internal flow dynamics can be successfully simulated using the modelling package KarstMod. The modelling results indicate the relevance of matrix storage in determining the discharge behaviour of the spring, particularly during low‐flow periods. This research and the consequent results can contribute and initiate a better understanding and management of alpine karst aquifers considering climate change with more heavy rainfall events and also longer dry periods.The investigated karst system contributes to the transient atmospheric CO2 sink with about 270 t/a. Carbonate denudation rates vary between 23 and 47 mm/1000a. Rainfall‐discharge modelling results indicate the importance of matrix storage particularly during low‐flow periods. imageBundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347FP7 People: Marie‐Curie Actions http://dx.doi.org/10.13039/10001126

Error threshold in optimal coding, numerical criteria and classes of universalities for complexity

The free energy of the Random Energy Model at the transition point between ferromagnetic and spin glass phases is calculated. At this point, equivalent to the decoding error threshold in optimal codes, free energy has finite size corrections proportional to the square root of the number of degrees. The response of the magnetization to the ferromagnetic couplings is maximal at the values of magnetization equal to half. We give several criteria of complexity and define different universality classes. According to our classification, at the lowest class of complexity are random graph, Markov Models and Hidden Markov Models. At the next level is Sherrington-Kirkpatrick spin glass, connected with neuron-network models. On a higher level are critical theories, spin glass phase of Random Energy Model, percolation, self organized criticality (SOC). The top level class involves HOT design, error threshold in optimal coding, language, and, maybe, financial market. Alive systems are also related with the last class. A concept of anti-resonance is suggested for the complex systems.Comment: 17 page

Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVID‐19 and severe respiratory insufficiency. METHODS: Investigator‐initiated, randomized, open‐label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID‐19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72 h. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non‐invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7–71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference −5.1 kPa [95% CI −10.2, −0.04] p = .05). The 28‐day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06–2.07, p = .26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72 h with no differences for other outcomes

Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis

The KIT D816V mutation is found in >80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. Therefore, KIT D816V represents a prime therapeutic target for SM. Here, we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM and mast cell leukemia to develop a patient-specific SM disease model for mechanistic and drug-discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor, and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, a US Food and Drug Administration-approved angiokinase inhibitor that targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the adenosine triphosphate binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V-targeted therapy of advanced SM.Peer reviewe

Inhibitor-Sensitive FGFR1 Amplification in Human Non-Small Cell Lung Cancer

Background Squamous cell lung carcinomas account for approximately 25% of new lung carcinoma cases and 40,000 deaths per year in the United States. Although there are multiple genomically targeted therapies for lung adenocarcinoma, none has yet been reported in squamous cell lung carcinoma. Methodology/Principal Findings Using SNP array analysis, we found that a region of chromosome segment 8p11-12 containing three genes–WHSC1L1, LETM2, and FGFR1–is amplified in 3% of lung adenocarcinomas and 21% of squamous cell lung carcinomas. Furthermore, we demonstrated that a non-small cell lung carcinoma cell line harboring focal amplification of FGFR1 is dependent on FGFR1 activity for cell growth, as treatment of this cell line either with FGFR1-specific shRNAs or with FGFR small molecule enzymatic inhibitors leads to cell growth inhibition. Conclusions/Significance These studies show that FGFR1 amplification is common in squamous cell lung cancer, and that FGFR1 may represent a promising therapeutic target in non-small cell lung cancer.Novartis Pharmaceuticals CorporationAmerican Lung AssociationUniting Against Lung CancerSara Thomas Monopoli FundSeaman FoundationIndia. Dept. of BiotechnologyNational Lung Cancer Partnershi