The study of doping market: how to produce intelligence from Internet forums

Despite the predominant role played by Internet in the distribution of doping substances, little is currently known about the online offer of doping products. Therefore, the study focuses on the detection of doping substances and suppliers discussed in Internet forums. It aims at having a comprehensive understanding of products and sellers to lead an operational monitoring of the online doping market. Thirteen community forums on the Internet were investigated and one million topics were extracted with source code scrappers. Then, a semantic analysis was conducted with a semi-automatic process to classify the relevant words according to doping matters. Additionally, the ranking of doping products, active substances and suppliers in regards to the number of contributors to the forums were established and analyzed over time. Finally, promotion methods of suppliers were evaluated. The results show that anabolic androgenic steroids, used to enhance body image and performance, are the most discussed type of products. A temporal analysis illustrates the stability of the most popular products as well as the emergence of new products such as peptides (e.g. CJC-1295). 327 suppliers were detected, mostly with dedicated websites or direct sales by e-mail as selling methods. Globally, the implemented methodology shows its ability to detect products and suppliers as well as to follow their temporal trends. The intelligence will serve the definition of online monitoring strategies (e.g. the selection of appropriate keywords). Additionally, it also allows the adjustment of customs inspection strategies and anti-doping analysis by monitoring the popular and emerging substances

Review of health-related quality of life data in multiple myeloma patients treated with novel agents

In multiple myeloma (MM), health-related quality of life (HRQoL) data is becoming increasingly important, owing to improved survival outcomes and the impact of treatment-related toxicity on HRQoL. Researchers are more frequently including HRQoL assessments in clinical trials, but analysis and reporting of this data has not been consistent. A systematic literature review assessed the effect of novel agents (thalidomide, bortezomib and lenalidomide) on HRQoL in MM patients, and evaluated the subsequent reporting of these HRQoL results. A relatively small body of literature addresses HRQoL data in MM patients treated with novel MM therapeutic agents: 9 manuscripts and 15 conference proceedings. The literature demonstrates the complementary value of HRQoL when assessing clinical response, progression, overall survival and toxicity. However, weaknesses and inconsistencies in analysis and presentation of HRQoL data were observed, often complicating interpretation of the impact of treatment on HRQoL in MM. Further evaluation of HRQoL in MM patients treated with novel agents is required in larger cohorts, and ideally in head-to-head comparative studies. Additionally, the development of standardised MM-specific best practice guidelines in HRQoL data collection and analysis is recommended. These would ensure that future data are more useful in guiding predictive models and clinical decisions

Saturation of dephasing time in mesoscopic devices produced by a ferromagnetic state

We consider an exchange model of itinerant electrons in a Heisenberg ferromagnet and we assume that the ferromagnet is in a fully polarized state. Using the Holstein-Primakoff transformation we are able to obtain a boson-fermion Hamiltonian that is well-known in the interaction between light and matter. This model describes the spontaneous emission in two-level atoms that is the proper decoherence mechanism when the number of modes of the radiation field is taken increasingly large, the vacuum acting as a reservoir. In the same way one can see that the interaction between the bosonic modes of spin waves and an itinerant electron produces decoherence by spin flipping with a rate proportional to the size of the system. In this way we are able to show that the experiments on quantum dots, described in D. K. Ferry et al. [Phys. Rev. Lett. {\bf 82}, 4687 (1999)], and nanowires, described in D. Natelson et al. [Phys. Rev. Lett. {\bf 86}, 1821 (2001)], can be understood as the interaction of itinerant electrons and an electron gas in a fully polarized state.Comment: 10 pages, no figure. Changed title. Revised version accepted for publication in Physical Review

DOSE REQUIREMENTS AND PLASMA CONCENTRATIONS OF PIPECURONIUM DURING BILATERAL RENAL EXCLUSION AND ORTHOTOPIC LIVER TRANSPLANTATION IN PIGS

We have studied five pigs undergoing bilateral clamping of the renal pedicles, seven pigs undergoing orthotopic liver transplantation and three control animals without surgery in order to examine the roles of the kidney and liver in the plasma clearance of pipecuronium. An i.v. infusion of pipecuronium was controlled to maintain a constant 90-95 % twitch depression throughout the investigation. The right sciatic nerve was stimulated continuously with supra-maximal stimuli at 0.1 Hz and the force of the corresponding evoked isometric muscle contraction was recorded continuously. Control pigs needed an infusion rate of pipecuronium 8-10.7 μg kg−1 min−1. In the renal group, it was necessary to reduce the infusion rate of pipecuronium by about 25% after clamping both renal vascular pedicles (P < 0.05 compared with controls); in pigs undergoing liver transplantation, it was necessary to reduce the rate by approximately 80% after clamping hepatic vessels (P < 0.05 compared with controls and from the period after clamping of renal vessels). After hepatic recirculation, the infusion rate of pipecuronium was increased progressively to a rate which corresponded to 50% of baseline values (P < 0.05 compared with the anhepatic phase and from controls). Plasma concentrations of pipecuronium were comparable in the three animal groups and did not change significantly during the study. These data suggest that the liver plays a more important role than the kidney in the plasma clearance of pipecuronium in pig

Electron transport and energy relaxation in dilute magnetic alloys

We consider the effect of the RKKY interaction between magnetic impurities on the electron relaxation rates in a normal metal. The interplay between the RKKY interaction and the Kondo effect may result in a non-monotonic temperature dependence of the electron momentum relaxation rate, which determines the Drude conductivity. The electron phase relaxation rate, which determines the magnitude of the weak localization correction to the resistivity, is also a non-monotonic function of temperature. For this function, we find the dependence of the position of its maximum on the concentration of magnetic impurities. We also relate the electron energy relaxation rate to the excitation spectrum of the system of magnetic impurities. The energy relaxation determines the distribution function for the out-of-equilibrium electrons. Measurement of the electron distribution function thus may provide information about the excitations in the spin glass phase.Comment: 15 pages, 5 figure

The C5 variant of the butyrylcholinesterase tetramer includes a noncovalently bound 60 kDa lamellipodin fragment

© 2017 by the authors. Licensee MDPI. Humans with the C5 genetic variant of butyrylcholinesterase (BChE) have 30–200% higher plasma BChE activity, low body weight, and shorter duration of action of the muscle relaxant succinylcholine. The C5 variant has an extra, slow-moving band of BChE activity on native polyacrylamide gel electrophoresis. This band is about 60 kDa larger than wild-type BChE. Umbilical cord BChE in 100% of newborn babies has a C5-like band. Our goal was to identify the unknown, 60 kDa protein in C5. Both wild-type and C5 BChE are under the genetic control of two independent loci, the BCHE gene on Chr 3q26.1 and the RAPH1 (lamellipodin) gene on Chr 2q33. Wild-type BChE tetramers are assembled around a 3 kDa polyproline peptide from lamellipodin. Western blot of boiled C5 and cord BChE showed a positive response with an antibody to the C-terminus of lamellipodin. The C-terminal exon of lamellipodin is about 60 kDa including an N-terminal polyproline. We propose that the unknown protein in C5 and cord BChE is encoded by the last exon of the RAPH1 gene. In 90% of the population, the 60 kDa fragment is shortened to 3 kDa during maturation to adulthood, leaving only 10% of adults with C5 BChE

Purification of recombinant human butyrylcholinesterase on Hupresin®

© 2018 Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin® was evaluated for its ability to purify truncated, recombinant human butyrylcholinesterase (rHuBChE) expressed in a stably transfected Chinese Hamster Ovary cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin® eluted with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin® binds AChE so tightly that AChE is not released with buffers, but is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE

Microscopic mechanisms of dephasing due to electron-electron interactions

We develop a non-perturbative numerical method to study tunneling of a single electron through an Aharonov-Bohm ring where several strongly interacting electrons are bound. Inelastic processes and spin-flip scattering are taken into account. The method is applied to study microscopic mechanisms of dephasing in a non-trivial model. We show that electron-electron interactions described by the Hubbard Hamiltonian lead to strong dephasing: the transmission probability at flux $\Phi=\pi$ is high even at small interaction strength. In addition to inelastic scattering, we identify two energy conserving mechanisms of dephasing: symmetry-changing and spin-flip scattering. The many-electron state on the ring determines which of these mechanisms will be at play: transmitted current can occur either in elastic or inelastic channels, with or without changing the spin of the scattering electron.Comment: 11 pages, 16 figures Submitted to Phys. Rev.

Lysosome-mediated processing of chromatin in senescence

Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression