A Bayes-competing risk model for the use of expert judgement in reliability estimation

In an analysis of the reliability of heat exchangers, a number of causes of failure and a number of potential failure patterns were identified. To allow a simplification of the analysis, five independent groups of failure causes were defined and formed the basis of a competing risks model. Further, lack of data and poor quality data required the experience of ‘experts’ to be used in a quantitative way through Bayesian methods. Lastly, to simplify the elicitation of the prior densities, a shape, scale and location parameter model for the failure time distributions was adopted

Проектирование автоматизированной системы управления блочно-кустовой насосной станции

Данная работа является проектом разработки автоматизированной компьютерной системы управления. Представлен выбор технических и программных средств, математический аппарат и программное обеспечение при проектирование автоматизированных систем управления SCADA. В работе отражены физические основы работы устройств АС, протоколов и интерфейсов систем автоматизации технологических процессов, требования ГОСТ по разработке технической документации проектов АС.This work is a project for the development of an automated computer control system. The choice of hardware and software, mathematical apparatus and software for the design of automated control systems SCADA. The work reflects the physical basis of the AC devices, protocols and interfaces of process automation systems, the requirements of GOST for the development of technical documentation of AC projects

Splicing factor YBX1 mediates persistence of JAK2-mutated neoplasms

Janus kinases (JAKs) mediate responses to cytokines, hormones and growth factors in haematopoietic cells. The JAK gene JAK2 is frequently mutated in the ageing haematopoietic system and in haematopoietic cancers. JAK2 mutations constitutively activate downstream signalling and are drivers of myeloproliferative neoplasm (MPN). In clinical use, JAK inhibitors have mixed effects on the overall disease burden of JAK2-mutated clones, prompting us to investigate the mechanism underlying disease persistence. Here, by in-depth phosphoproteome profiling, we identify proteins involved in mRNA processing as targets of mutant JAK2. We found that inactivation of YBX1, a post-translationally modified target of JAK2, sensitizes cells that persist despite treatment with JAK inhibitors to apoptosis and results in RNA mis-splicing, enrichment for retained introns and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signalling. In combination with pharmacological JAK inhibition, YBX1 inactivation induces apoptosis in JAK2-dependent mouse and primary human cells, causing regression of the malignant clones in vivo, and inducing molecular remission. This identifies and validates a cell-intrinsic mechanism whereby differential protein phosphorylation causes splicing-dependent alterations of JAK2-ERK signalling and the maintenance of JAK2(V617F) malignant clones. Therapeutic targeting of YBX1-dependent ERK signalling in combination with JAK2 inhibition could thus eradicate cells harbouring mutations in JAK2

The dinoflagellate cyst genera <i>Achomosphaera</i> Evitt 1963 and <i>Spiniferites</i> Mantell 1850 in Pliocene to modern sediments: a summary of round table discussions

We present a summary of two round-table discussions held during two subsequent workshops in Montreal (Canada) on 16 April 2014 and Ostend (Belgium) on 8 July 2015. Five species of the genus Achomosphaera Evitt 1963 and 33 of the genus Spiniferites Mantell 1850 emend. Sarjeant 1970 occuring in Pliocene to modern sediments are listed and briefly described along with remarks made by workshop participants. In addition, several holotypes and topotypes are reillustrated. Three species previously assigned to Spiniferites are here considered/accepted as belonging to other genera: Impagidinium inaequalis (Wall and Dale in Wall et al. 1973) Londeix et al. 2009, Spiniferites rubinus (Rossignol 1962 ex Rossignol 1964) Sarjeant 1970, and Thalassiphora balcanica Baltes & 1971. This summary forms the basis for a set of papers that follows, where points raised during the workshops are explored in greater detail

Follistatin-controlled activin-HNF4 alpha-coagulation factor axis in liver progenitor cells determines outcome of acute liver failure

Background and Aims In patients with acute liver failure (ALF) who suffer from massive hepatocyte loss, liver progenitor cells (LPCs) take over key hepatocyte functions, which ultimately determines survival. This study investigated how the expression of hepatocyte nuclear factor 4 alpha (HNF4 alpha), its regulators, and targets in LPCs determines clinical outcome of patients with ALF. Approach and Results Clinicopathological associations were scrutinized in 19 patients with ALF (9 recovered and 10 receiving liver transplantation). Regulatory mechanisms between follistatin, activin, HNF4 alpha, and coagulation factor expression in LPC were investigated in vitro and in metronidazole-treated zebrafish. A prospective clinical study followed up 186 patients with cirrhosis for 80 months to observe the relevance of follistatin levels in prevalence and mortality of acute-on-chronic liver failure. Recovered patients with ALF robustly express HNF4 alpha in either LPCs or remaining hepatocytes. As in hepatocytes, HNF4 alpha controls the expression of coagulation factors by binding to their promoters in LPC. HNF4 alpha expression in LPCs requires the forkhead box protein H1-Sma and Mad homolog 2/3/4 transcription factor complex, which is promoted by the TGF-beta superfamily member activin. Activin signaling in LPCs is negatively regulated by follistatin, a hepatocyte-derived hormone controlled by insulin and glucagon. In contrast to patients requiring liver transplantation, recovered patients demonstrate a normal activin/follistatin ratio, robust abundance of the activin effectors phosphorylated Sma and Mad homolog 2 and HNF4 alpha in LPCs, leading to significantly improved coagulation function. A follow-up study indicated that serum follistatin levels could predict the incidence and mortality of acute-on-chronic liver failure. Conclusions These results highlight a crucial role of the follistatin-controlled activin-HNF4 alpha-coagulation axis in determining the clinical outcome of massive hepatocyte loss-induced ALF. The effects of insulin and glucagon on follistatin suggest a key role of the systemic metabolic state in ALF.Cancer Signaling networks and Molecular Therapeutic

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR