Miracle-dz/UniFAR-FTUs huggingface dataset:
Arsenic trioxide: An anti cancer missile with multiple warheads

Abstract The proven efficacy of ATO in the treatment of APL and the emerging importance of ATO in other diseases prompted extensive studies of the mechanisms of action of ATO in APL and in other types of cancers. In this review we will focus on downstream events in ATO-induced intrinsic and extrinsic apoptotic pathways with an emphasis on the role of pro-apoptotic and anti-apoptotic proteins and the role of p53 in ATO-induced apoptosis including its effect on cell cycle, its anti-mitotic effect and the role of apoptosis inducing factors (AIF) in ATO-induced apoptosis, chromatin condensation and nuclear fragmentation in myeloma cells as a model.
Morphology and Notes on Morphogenesis during Cell Division of Deviata polycirrata n. sp. and of Deviata bacilliformis ( Gelei, 1954) Eigner, 1995 (Ciliophora: Kahliellidae) from Argentina

ABSTRACT. Described herein are the morphology and certain morphogenetic stages of a new freshwater ciliate species, Deviata polycirrata n. sp. , and of Deviata bacilliformis recorded in the soil of a dried temporary pond from Argentina. Ciliates were studied alive and after silver impregnation with Protargol. Deviata polycirrata n. sp. measures 130–180 × 45–70 μm in vivo. The species possesses 8–9 long cirral rows on the right and 9–13 on the left of the oral zone, and 3 dorsal rows of dikinetids. The adoral zone is composed of 39–48 membranelles. There are four macronuclear nodules and usually two micronuclei. A single contractile vacuole is located equatorially on the left body margin. This new species mainly differs from its congeners in having a higher number of cirral rows, the three long dorsal rows of dikinetids (vs. usually one to two dorsal rows of dikinetids), and a higher number of adoral membranelles. The other species reported here, D. bacilliformis, is recorded for the first time in Argentina. Unlike previous observations on this species, on the dorsal surface there are cirral rows that are preceded by cilia (combined cirral rows), and stomatogenesis begins with the proliferation of non‐ciliferous basal bodies some distance posterior to the buccal vertex.
Modelling of Human Cardiovascular Response to Moderate Exercise

This paper investigates the steady state relationships between key central cardiovascular variables (i.e. stroke volume, heart rate, total peripheral resistance and cardiac output) and oxygen uptake rate (V̇ O2) during moderate incremental exercise. Ten untrained normal males exercised in an upright position on an electronically braked cycle ergometer with constant workloads ranging from 25 Watt to 125 Watt. Throughout the experiment V̇ O2 was determined breath by breath and heart rate (HR) was monitored beat by beat. During the last minute of each exercise session, cardiac output was measured beat by beat using a novel non-invasive ultrasound based device and blood pressure was measured using a tonometric measurement device. Based on the analysis of experimental data, nonlinear steady state relationships between key central cardiovascular variables and V̇ O2 were qualitatively observed except for HR which increased linearly as a function of increasing V̇ O2. Quantitative descriptions of these complex nonlinear behaviours were provided by nonparametric models which were obtained by using Support Vector Regression.
Ustekinumab for severe atopic dermatitis: an important negative study

1 Bagel J, Tyring S, Rice KC et al. Open-label study of etanercept treatment in patients with moderate-to-severe plaque psoriasis who lost a satisfactory response to adalimumab. Br J Dermatol 2017; 177:411–8. 2 Vender R. An open-label, prospective cohort pilot study to evaluate the efficacy and safety of etanercept in the treatment of moderate to severe plaque psoriasis in patients who have not had an adequate response to adalimumab. J Drugs Dermatol 2011; 10:396–402. 3 Chastek B, Fox KM, Watson C et al. Psoriasis treatment patterns with etanercept and adalimumab in a United States health plan population. J Dermatolog Treat 2013; 24:25–33. 4 Puig L. Treatment of moderate to severe plaque psoriasis with biologics: analysis of the additional cost of temporary dose escalation vs switch to another biologic after failure of maintenance therapy. Actas Dermosifiliogr 2014; 105:401–12. 5 Abrouk M, Nakamura M, Zhu TH et al. The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients. J Dermatolog Treat 2017; 1–7. 6 Elewski BE, Puig L, Mordin M et al. Psoriasis patients with Psoriasis Area and Severity Index (PASI) 90 response achieve greater healthrelated quality-of-life improvements than those with PASI 75–89 response: results from two phase 3 studies of secukinumab. J Dermatolog Treat 2017; 7:1–8. 7 Warren RB, Mrowietz U, von Kiedrowski R et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 389:528–37. 8 Express Script Drug Trend Report 2016. Available at: http:// www.lab. express-scripts.com/lab/drug-trend-report (last accessed 6 April 2017). 9 Sagonowsky E. Amgen hikes prices by single digits, with Enbrel matching AbbVie’s Humira boost. Fiercepharma 23 January 2017. Available at: http://www.fiercepharma. com/pharma/amgenboosts-enbrel-price-days-after-abbvie-hike-humira (last accessed 6 April 2017). 10 Ahn CS, Gustafson CJ, Sandoval LF et al. Cost effectiveness of biologic therapies for plaque psoriasis. Am J Clin Dermatol 2013; 14:315–26.
Aerothermodynamic Aspects of Railgun-Assisted Launches of Projectiles With Sub- and Low-Earth-Orbit Payloads

A Railgun-concept for the launch of small payloads into low-Earth orbits is currently under investigation. The first major project milestone foresees a 32-MJ railgun system able to launch nonpropelled projectiles with experiments for high-atmospheric research to an altitude of 115 km. This will be followed by a system to launch single-stage rocket-propelled projectiles to put in orbit nanosatellites using a 3.4-GJ railgun with a length of 180 m. One of the main issues to be investigated is the extreme thermal conditions the projectile's surfaces are exposed to, namely high temperatures and high thermal loads. These are caused by friction and turbulent flow properties, when the projectile rushes through the dense Earth's atmosphere in less than 30 s. The important questions to be answered for the design of a hypersonic projectile are the determination of the duration, magnitude, and location of the maximum temperatures with respect to the projectile's surface and its corresponding internal structure. For the determination of the complicated physical conditions, a two-step approach is used. In a so-called predesign phase, the HF3T code of the DLR is applied to estimate time-dependent temperature changes on the projectile's surface and/or within the material's structure as a function of the trajectory parameters. Finally, the three-degree-of-freedom trajectory program TRAJECTORY 3D of DLR is used to generate a detailed time-dependent data set, which includes the values for projectile velocity, Mach and Reynolds numbers, and atmospheric properties as a function of altitude. This data set is exchangeable with the TAU code of DLR for the solution of the Navier-Stokes equations, enabling pseudo-unsteady flow solutions along the trajectory. The solutions resulting from both approaches are then compared with emphasis on the surface temperature distributions. This strategy allows the verification of the feasibility of the proposed design solution for the railgun launched hypersonic projectiles
Characterization of the substrate binding site in rat liver 3alpha-hydroxysteroid/dihydrodiol dehydrogenase. The roles of tryptophans in ligand binding and protein fluorescence.

Rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), a member of the aldoketoreductase superfamily, inactivates circulating steroid hormones using NAD(P)H as cofactor. Despite determination of the 3alpha-HSD.NADP+ binary complex structure, the functional elements that dictate the binding of steroids remain unclear (Bennett, M.J., Schlegel, B.P., Jez, J.M., Penning, T.M., and Lewis, M. (1996) Biochemistry 35, 10702-10711). Two tryptophans (Trp86 and Trp227) near the active site may have roles in substrate binding, and their fluorescence may be quenched upon binding of NADPH. Trp86 is located within an apolar cleft, while Trp227 is found on an opposing loop near the active site. A third tryptophan, Trp148, is on the periphery of the structure. To investigate the roles of these tryptophans in protein fluorescence and ligand binding, we generated three mutant enzymes (W86Y, W148Y, and W227Y) by site-directed mutagenesis. Spectroscopic measurements on these proteins showed that Trp148 contributed the most to the enzyme fluorescence spectra, with Trp227 adding the least. Trp86 was identified as the tryptophan quenched by bound NADPH through an energy transfer mechanism. The W86Y mutant altered binding of cofactor (a 3-fold increase in Kd for NADPH) and steroid (a 7-fold increase in Kd for testosterone). This mutation also dramatically decreased the catalytic efficiency observed with one-, two-, and three-ring substrates and decreased the binding affinity for nonsteroidal anti-inflammatory drugs but had little effect on the binding of aldose reductase inhibitors. Interestingly, mutation of Trp227 significantly impaired steroid binding (a 22-fold increase in Kd for testosterone), but did not alter binding of cofactor, smaller substrates, or inhibitors. Kinetically, the W148Y mutant was similar to wild-type enzyme. Our results demonstrate that Trp86 and the apolar cleft is part of the substrate binding pocket. In addition, we propose a role for Trp227 and its associated loop in binding steroids, but not small substrates or inhibitors, most likely through interaction with the C- and D-rings of the steroid. This work provides the first evidence that tryptophans on opposite sides of the apolar cleft are part of the steroid binding pocket and suggests how the enzyme may discriminate between nonsteroidal anti-inflammatory drugs and aldose reductase inhibitors like zopolrestat. A model of how androstanedione binds in the apolar cleft is developed. These data provide further evidence that loop structures in members of the aldoketoreductase superfamily are critical determinants of ligand binding.
Enucleative surgery in an infant with giant cystic nephroma.

In 1992 we began a pilot study investigating whether nephron sparing surgery is a reasonable alternative to nephrectomy in select children with unilateral primary renal tumor.1 In that study when nephron sparing surgery was not performed in vivo, the feasibility of tumor enucleation was assessed ex vivo. In 1 infant a cystic partially differentiated nephroblastoma was easily enucleated ex vivo, leaving an amount of renal parenchyma that was much greater than assessed on preoperative imaging. Therefore, we elected to attempt in vivo enucleation in an infant with a giant central multilocular cystic renal tumor. We report the results of the procedure and discuss treatment details.
A cubic matrix-fracture geometry model for radial tracer flow in naturally fractured reservoirs

This study presents a general solution for the radial flow of tracers in naturally fractured reservoirs, with cubic blocks matrix-fracture geometry. Continuous and finite step injection of chemical and radioactive tracers are considered. The reservoir is treated as being composed of two regions: a mobile where dispersion and convection take place and a stagnant where only diffusion and adsorption are allowed. Radioactive decay is considered in both regions. The model of this study is thoroughly compared under proper simplified conditions to those previously presented in the literature. The coupled matrix to fracture solution in the Laplace space is numerically inverted by means of the Crump algorithm. A detailed validation of the model with respect to solutions previously presented and/or simplified physical conditions solutions (i.e., homogeneous case) or limit solutions (i.e., naturally fractured nearly homogeneous) was carried out. The influence of the three of the main dimensionless parameters that enter into the solution was carefully investigated. A comparison of results for three different naturally fractured systems, vertical fractures (linear flow), horizontal fractures (radial flow) and the cubic geometry model of this study, is presented.
THE MUTATION OF PSEUDOMONAS PUTREFACIENS TO GLUCOSE UTILIZATION AND ITS ENZYMATIC BASIS

Pseudomoas putrefaciens, an organism causing surface taint in butter, was discovered by Derby and Hammer (1931), who described it as producing acid readily from maltose and sucrose, but not from glucose, in the conventional indicator-broth media. Later Long and Hammer (1941) and Wolochow, Thornton, and Hood (1942) reported that acid production from glucose was highly variable. In the sixth edition of Bergey's Manual (1948) this organism is listed as having "no action on glucose. " Particularly in view of the ready utilization of maltose and sucrose by P. putrefaciens, a clarification of the question of its ability to attack glucose appeared desirable.
The role of decapping proteins in the miRNA accumulation in Arabidopsis thaliana

Decapping 1 (DCP1), Decapping 2 (DCP2) and VARICOSE (VCS) are components of the decapping complex that removes the 7-methyl-guanosine 5′-diphosphate from the 5′ end of mRNAs. In animals, the decapping proteins are involved in miRNA-mediated gene silencing, whereas in plants the roles of the decapping proteins in the miRNA pathway are not well understood. Here we demonstrated that the accumulation of miRNAs decreased in dcp1, dcp2 and vcs mutants, indicating that DCP1, DCP2 and VCS are important for the miRNA pathway in Arabidopsis thaliana. The primary miRNAs (pri-miRNAs) did not increase and miRNA biogenesis components did not decrease in these mutants, suggesting that the miRNA decrease in decapping mutants is not due to the defect of pri-miRNA processing. We showed that the accumulation of miRNA targets increased concomitantly with the decrease of miRNA in the decapping mutants. Our results suggested that the seedling lethal phenotypes in the dcp1, dcp2 and vcs mutants are caused not only by the defect in decapping, but also by the disruption of miRNA-mediated gene regulation.
The regulation of post-germinative transition from the cotyledon- to vegetative-leaf stages by microRNA-targeted SQUAMOSA PROMOTER-BINDING PROTEIN LIKE13 in Arabidopsis

Abstract Germination and early seedling development are critical for successful stand establishment of plants. Following germination, the cotyledons, which are derived from embryonic tissue, emerge from the seed. Arabidopsis seedlings at post-germinative stages are supported mainly by the supply of nutrition from the cotyledons until vegetative leaves emerge and initiate photosynthesis. The switch to autotrophic growth is a significant transition at the post-germinative stage. Here, we provide evidence that down-regulation of SQUAMOSA PROMOTER-BINDING PROTEIN LIKE13 (SPL13) by microRNA156 (miR156) plays an important role in the regulation of the post-germinative switch from the cotyledon stage to the vegetative-leaf stage. Silent mutations created in the SPL13 sequence in the region that is complementary to the miR156 sequence caused the deregulation of the mutant form of SPL13 (mSPL13) mRNA from miR156. Mutant seedlings over-accumulated miRNA-resistant messages and exhibited a delay in the emergence of vegetative leaves compared to wild-type seedlings. The delay was not observed in control transgenic plants expressing non-mutated SPL13, indicating that the phenotype was caused specifically by the silent mutations and deregulation of SPL13 from miR156. Characterization of the SPL13 promoter indicated that this gene is expressed mainly in the hypocotyl and affects leaf primordium development. These results suggest that the repression of SPL13 by miR156 is essential for normal post-germinative growth in Arabidopsis.
Attentional Activation of the Cerebellum Independent of Motor Involvement

The cerebellum traditionally has been viewed as a neural device dedicated to motor control. Although recent evidence shows that it is involved in nonmotor operations as well, an important question is whether this involvement is independent of motor control and motor guidance. Functional magnetic resonance imaging was used to demonstrate that attention and motor performance independently activate distinct cerebellar regions. These findings support a broader concept of cerebellar function, in which the cerebellum is involved in diverse cognitive and noncognitive neurobehavioral systems, including the attention and motor systems, in order to anticipate imminent information acquisition, analysis, or action.
Unique strainmeter observations of Vulcanian explosions, Soufrière Hills Volcano, Montserrat, July 2003

Five Vulcanian explosions were triggered by collapse of the Soufrière Hills Volcano lava dome in 2003. We report strainmeter data for three explosions, characterized by four stages: a short transition between the onset of disturbance and a pronounced change in strain; a quasi‐linear ramp accounting for the majority of strain change; a more gradual continued decline of strain to a minimum value; and a strain recovery phase lasting hours. Remarkable ∼800 s barometric gravity waves propagated at ∼30 m s−1. Eruption volumes estimated from plume height and strain data are 0.32–0.42 × 106, 0.26–0.49 × 106, and 0.81–0.84 × 106 m3, for Explosions 3–5 respectively, consistent with quasi‐cylindrical conduit drawdown <2 km. The duration of vigorous explosion is given by the strain signature, indicating mass fluxes of order 107 kg s−1. Conduit pressures released reflect static weight of porous gas‐charged magma, and exsolution‐generated overpressures of order 10 MPa.
The Association Between Maxillary Sinus Mucosal Thickening and Periapical Radiolucency Using Cone-Beam Computed Tomography Scanning: A Retrospective Study

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Dopamine neurons of the monkey midbrain: contingencies of responses to stimuli eliciting immediate behavioral reactions.

1. This study investigates the behavioral conditions in which dopamine (DA) neurons of substantia nigra and adjoining areas A8 and A10 respond with impulses to visual and auditory trigger stimuli eliciting immediate arm- and eye-movement reactions. 2. In a formal task, the rapid opening of the door of a small, food-containing box located at eye level ahead of the animal served as visible and audible trigger stimulus. Most DA neurons on the contralateral side responded to this stimulus with a short burst of impulses with median onset latency of 50 ms and duration of 90 ms (75% of 164 neurons). Similar responses were seen in a comparable fraction of DA neurons during ipsilateral task performance, suggesting that responses were not specific for the limb being used. 3. When the sensory components of the door opening stimulus were separated, DA neurons typically responded in a similar manner to the moving visual stimulus of the opening door, the low-intensity sliding noise of the opening door, and the 1-kHz sound of 90-92 dB intensity emitted from a distant source at the onset of door opening. Responses to each component alone were lower in magnitude than to all three together. 4. In a variation of the task, a neighboring, identical food box opened in random alternation with the other box but without permitting animals to reach out (asymmetric, direct-reaction go/no-go task). With each sensory component, DA neurons typically responded both to opening of go and no-go boxes. Responses were enhanced when stimuli elicited limb movements in go trials. 5. Monkeys reacted to door opening with target-directed saccadic eye movements in the majority of both go and no-go trials. Neuronal responses were equally present during the occasional absence of eye movements. Thus responses were not specific for the initiation of individual arm or eye movements. 6. Neuronal responses were absent when the same stimuli occurred outside of the behavioral task with target-direct arm and eye movements lacking. This shows that responses were not of purely sensory nature but were related to the capacity of the stimulus for eliciting behavioral reactions. 7. In a variation of the go/no-go task, an instruction light illuminated 2-3 s before door opening prepared the animal to perform the reaching movement on door opening or to refrain from moving (asymmetric, instruction-dependent go/no-go task). (ABSTRACT TRUNCATED AT 400 WORDS)
Influence of Moderate Alcohol Intake on Thiopental Anesthesia

The relationship between alcohol intake over the week preceding anesthesia and various anesthetic parameters was examined in 119 women scheduled for termination of pregnancy under thiopental‐nitrous oxide anesthesia. In terms of pure alcohol, the weekly intake was 1.0±1.09 ml·kg‐1 (mean±s.d.), range 0–5.93. i.e. below average consumption in Denmark. Alcohol intake was negatively correlated with anesthetic sleeping time (P <0.01). Time and quality of anesthesia induction and frequency of anesthetic complications were not significantly correlated with the use of alcohol. Preanesthetic anxiety was not significantly correlated with any of the above data. Induction time and postoperative awareness were positively and sleeping time negatively correlated with age (P <0.05). The results indicate cross‐tolerance between alcohol and thiopental, even when the regular intake of the former is low, and increasing thiopental requirements with increasing age.
Pricing of Products and Complementary Services: A Study of the Online Game Industry

We model a monopolist who offers a product and a complementary service, where only the latter exhibits positive network externalities. We focus on the online game industry as a representative case in which the product (the game), unlike the service (access to the interactive online play mode), has zero marginal cost, and consider two-potential pricing strategies: 1) the bundle pricing, in which the vendor charges a single price for the product and the service; and 2) the separate pricing, in which the vendor sets the prices of the product and the service separately. We find that, in contrast to the common result in the bundling literature, bundling may increase consumer surplus, while the monopolist chooses not to offer the bundle. We offer theoretical evidence that this is due to the presence of network externalities.
Probing bacterial pathogenesis with genetics, genomics, and chemical biology: past, present, and future approaches

Classical genetic approaches for studying bacterial pathogenesis have provided a solid foundation for our current understanding of microbial physiology and the interactions between pathogen and host. During the past decade however, advances in several arenas have expanded the ways in which the biology of pathogens can be studied. This review discussed the impact of these advances on bacterial genetics, including the application of genomics and chemical biology to the study of pathogenesis.