Self-Referential Noise and the Synthesis of Three-Dimensional Space

Generalising results from Godel and Chaitin in mathematics suggests that self-referential systems contain intrinsic randomness. We argue that this is relevant to modelling the universe and show how three-dimensional space may arise from a non-geometric order-disorder model driven by self-referential noise.Comment: Figure labels correcte

Riociguat: Clinical research and evolving role in therapy

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as an inhibitor of cGMP metabolism. As with other approved therapies for PAH, riociguat has antifibrotic, antiproliferative and anti-inflammatory effects, in addition to vasodilatory properties. This has led to further clinical studies in patients who do not achieve a satisfactory clinical response with phosphodiesterase type-5 inhibitors. Riociguat has also been evaluated in patients with World Health Organization group 2 and 3 pulmonary hypertension, and other conditions including diffuse cutaneous systemic sclerosis, Raynaud\u27s phenomenon and cystic fibrosis. This review evaluates the results of the original clinical trials of riociguat for the treatment of PAH and CTEPH, and summarises the body of work that has examined the safety and efficacy of riociguat for the treatment of other types of pulmonary hypertension

The Burst-Like Behavior of Aseismic Slip on a Rough Fault: The Creeping Section of the Haiyuan Fault, China

Recent observations suggesting the influence of creep on earthquakes nucleation and arrest are strong incentives to investigate the physical mechanisms controlling how active faults slip. We focus here on deriving generic characteristics of shallow creep along the Haiyuan fault, a major strike‐slip fault in China, by investigating the relationship between fault slip and geometry. We use optical images and time series of Synthetic Aperture Radar data to map the surface fault trace and the spatiotemporal distribution of surface slip along the creeping section of the Haiyuan fault. The fault trace roughness shows a power‐law behavior similar to that of the aseismic slip distribution, with a 0.8 roughness exponent, typical of a self‐affine regime. One possible interpretation is that fault geometry controls to some extent the distribution of aseismic slip, as it has been shown previously for coseismic slip along active faults. Creep is characterized by local fluctuations in rates that we define as creep bursts. The potency of creep bursts follows a power‐law behavior similar to the Gutenberg–Richter earthquake distribution, whereas the distribution of bursts velocity is non‐Gaussian, suggesting an avalanche‐like behavior of these slip events. Such similarities with earthquakes and lab experiments lead us to interpret the rich dynamics of creep bursts observed along the Haiyuan fault as resulting from long‐range elastic interactions within the heterogeneous Earth’s crust

Poly(ADP-ribosyl)ation Acts in the DNA Demethylation of Mouse Primordial Germ Cells Also with DNA Damage-Independent Roles

Poly(ADP-ribosyl)ation regulates chromatin structure and transcription driving epigenetic events. In particular, Parp1 is able to directly influence DNA methylation patterns controlling transcription and activity of Dnmt1. Here, we show that ADP-ribose polymer levels and Parp1 expression are noticeably high in mouse primordial germ cells (PGCs) when the bulk of DNA demethylation occurs during germline epigenetic reprogramming in the embryo. Notably, Parp1 activity is stimulated in PGCs even before its participation in the DNA damage response associated with active DNA demethylation. We demonstrate that PARP inhibition impairs both genome-wide and locus-specific DNA methylation erasure in PGCs. Moreover, we evidence that impairment of PARP activity causes a significant reduction of expression of the gene coding for Tet1 hydroxylases involved in active DNA demethylation. Taken together these results demonstrate new and adjuvant roles of poly(ADP-ribosyl)ation during germline DNA demethylation and suggest its possible more general involvement in genome reprogramming

To be or not to be a germ cell: The extragonadal germ cell tumor paradigm

In the human embryo, the genetic program that orchestrates germ cell specification in-volves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neo-plasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types

Riociguat: Mode of action and clinical development in pulmonary hypertension

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and the pivotal Phase III randomized clinical trials in PAH and CTEPH

Частотно-регулируемый электропривод погружного насоса

Цель работы – спроектировать регулируемый электропривод переменного тока для погружного центробежного насоса. В процессе работы был произведён расчёт и выбор электрооборудования для привода. Для управления электроприводом принята система управления асинхронным двигателем со скалярным принципом управления. Проведены исследования в области статики и динамики системы с помощью численного моделирования.The purpose of work - to design a regulated electric alternating current to the submersible centrifugal pump. In the process, the calculation was made and the selection of electrical equipment for the drive. To control the electric control system adopted by the asynchronous motor with a scalar control principle. Researches in the field of statics and dynamics of the system with the help of numerical simulation

Detection of IUPAC and IUPAC-like chemical names

Motivation: Chemical compounds like small signal molecules or other biological active chemical substances are an important entity class in life science publications and patents. Several representations and nomenclatures for chemicals like SMILES, InChI, IUPAC or trivial names exist. Only SMILES and InChI names allow a direct structure search, but in biomedical texts trivial names and Iupac like names are used more frequent. While trivial names can be found with a dictionary-based approach and in such a way mapped to their corresponding structures, it is not possible to enumerate all IUPAC names. In this work, we present a new machine learning approach based on conditional random fields (CRF) to find mentions of IUPAC and IUPAC-like names in scientific text as well as its evaluation and the conversion rate with available name-to-structure tools