Miracle-dz/UniFAR-FTUs huggingface dataset:
Keap1-dependent Proteasomal Degradation of Transcription Factor Nrf2 Contributes to the Negative Regulation of Antioxidant Response Element-driven Gene Expression*

Keap1 is a negative regulator of Nrf2, a bZIP transcription factor that mediates adaptation to oxidative stress. Previous studies suggested this negative regulation is a consequence of Keap1 controlling the subcellular distribution of Nrf2. We now report that Keap1 also controls the total cellular level of Nrf2 protein. In the RL34 non-transformed rat liver cell line, Nrf2 was found to accumulate rapidly in response to oxidative stress caused by treatment with sulforaphane, and the accumulation resulted from inhibition of proteasomal-mediated degradation of the bZIP protein. By heterologously expressing in COS1 cells epitope-tagged Nrf2 and an Nrf2ΔETGE mutant lacking the Keap1-binding site, in both the presence and absence of Keap1 we demonstrate that Nrf2 is subject to ubiquitination and proteasomal degradation independently of both Keap1 and the redox environment of the cell. In oxidatively stressed cells, this is the sole mechanism responsible for Nrf2 degradation. However, under homeostatic conditions Nrf2 is subject to a substantially more rapid mode of proteasomal degradation than it is in oxidatively stressed cells, and this rapid turnover of Nrf2 requires it to interact with Keap1. Within Nrf2, the N-terminal Neh2 domain is identified as the redox-sensitive degron. These data suggest that Keap1 negatively regulates Nrf2 by both enhancing its rate of proteasomal degradation and altering its subcellular distribution.
Design of a Nonlinear PID Neural Trajectory Tracking Controller for Mobile Robot based on Optimization Algorithm

This paper presents a trajectory tracking control algorithm for a nonholonomic wheeled mobile robot using optimization technique based nonlinear PID neural controller in order to follow a pre-defined a continuous path. As simple and fast tuning algorithms, particle swarm optimization algorithm is used to tune the nonlinear PID neural controller's parameters to find best velocity control actions for the mobile robot. Simulation results show the effectiveness of the proposed nonlinear PID control algorithm; this is demonstrated by the minimized tracking error and the smoothness of the velocity control signal obtained, especially with regards to the external disturbance attenuation problem.
The invasive plant Alliaria petiolata (garlic mustard) inhibits ectomycorrhizal fungi in its introduced range

1 Ectomycorrhizal (EM) fungi play key roles in forest ecosystems, but the potential effects of invasive plants on EM fungal communities have not been assessed. In this study, we tested whether the non‐mycorrhizal herbaceous plant Alliaria petiolata (garlic mustard) can alter the abundance of EM fungal communities in North America. 2 In three forests in New England, USA, we compared EM root tip abundance in soils where A. petiolata had invaded to adjacent areas without a history of A. petiolata invasion. At one site, we also intensively sampled EM root tip abundance across the edges of A. petiolata patches to determine the spatial pattern of A. petiolata effects on EM fungi. In a glasshouse experiment, we experimentally invaded soils with A. petiolata and Impatiens capensis, a native species and compared EM fungal colonization of white pine (Pinus strobus) seedlings grown in both soils. We also measured the effect of the A. petiolata allelochemical benzyl isothiocyanate on the growth of three species of EM fungi in pure culture. 3 In the field, EM fungal root tip biomass was lower in invaded soils, with the strongest reductions observed in forests dominated by conifers. Alliaria petiolata invasion did not have a significant effect on total root biomass. The influence of A. petiolata on EM fungal abundance in the field was localized, with the strongest inhibition observed within 10 cm of the edge of A. petiolata patches. 4 Pine seedlings growing in soils that were experimentally invaded with A. petiolata also had lower EM fungal root tip biomass compared to uninvaded soils. The native species I. capensis caused similar reductions in EM fungal colonization. Growth of pure cultures of all three species of EM fungi was completely inhibited by benzyl isothiocyanate. 5 Synthesis. Alliaria petiolata inhibits the growth of EM fungi in forests of its introduced range. Changes in EM fungal communities caused by the invasion of A. petiolata may influence tree seedling establishment and biogeochemical cycling.
Methyl-coenzyme M, an intermediate in methanogenic dissimilation of C1 compounds by Methanosarcina barkeri

Extracts of Methanosarcina barkeri possess a specific methyltransferase that catalyzes the transfer of the methyl group of methanol to 2-mercaptoethanesulfonic acid. Over a fourfold range in added 2-mercaptoethanesulfonic acid, the formation of 2-(methylthio)ethanesulfonic acid exhibited a 1:1 ratio to 2-mercaptoethanesulfonic acid added. This reaction required adenosine 5'-triphosphate; a maximal ratio (mole/mole) of 85 methyl groups was transferred per adenosine 5'-triphosphate added. The methyltransferase was found in extracts of methanol-grown cells as well as in extracts of hydrogen-grown cells. In extracts of cells grown on either substrate, 2-(methylthio)ethanesulfonic acid was formed from added methanol or methylamine but not from acetate.
TRANSITION MODELS TO ASSESS RISK FACTORS FOR NEW AND PERSISTENT TRYPANOSOME INFECTIONS IN CATTLE—ANALYSIS OF LONGITUDINAL DATA FROM THE GHIBE VALLEY, SOUTHWEST ETHIOPIA

The objective of this study was to apply transition models to distinguish between factors associated with both incident and persistent trypanosome infections. Data collected from 1,561 cattle were analyzed from a long-term study involving 8 herds in which both trypanosome infections (a total of 56,931 cattle sampling-months) and tsetse (Glossina spp.) challenge were monitored monthly from March 1986 to March 1998. Both pour-on and insecticide-target tsetse control programs and mass treatment with diminazene aceturate before tsetse control were associated with significant decreases in both incidence and persistence of trypanosome infection relative to noncontrol periods, as were seasonal and sex effects. The magnitudes of the effects were, however, often different for new and persistent infections. For persistence of infection, there were 2 trends. In general, the duration of infection increased during the study, despite the regular treatment with diminazene aceturate. The transition model had 2 major benefits. The first was to identify an increasing duration of infections with time, taking into account other factors associated with increasing infection risk. The second was to highlight different patterns in the effects of certain factors on new and persistent trypanosome infections.
Stemming the Tide of Suicide in Older White Men: A Call to Action

Preventing suicide has been identified as a national priority by recent commissions in the United States. Despite increased awareness of suicide as a public health problem, suicide in older adults remains a neglected topic in prevention strategies and research. This is especially true regarding elderly White men, who in terms of suicide rates have represented the most at-risk age group for the past half century. In light of the unprecedented aging of the United States as the baby boom generation enters late adulthood, suicide prevention initiatives that focus on aging males are needed to prevent a national crisis in geriatric mental health. This article provides a brief review of the perennially under-recognized reality of suicide in older men and prevention strategies that, if implemented, might help stem this rising tide of suicide in this vulnerable population.
Liver Ischemia: Apoptosis as a Central Mechanism of Injury

Injuries due to cold and warm (normothermic) ischemia remain an important source of morbidity and mortality in liver surgery and transplantation. While the mechanisms of injury are complex, involving apoptotic and necrotic types of cell death, accumulating evidence points to a central role for various apoptotic pathways in mediating cell death following ischemia. A number of antiapoptotic strategies have been shown to confer a high degree of protection, including improved animal survival following long ischemic insult. The future may lie in the identification of practical and effective antiapoptotic strategies to enhance tolerance to ischemic injury.
Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989–90 using a general practice database

Summary The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of 1989–90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21–92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups.
A Review of E-Payment System in E-Commerce

The Era of Information and Communication Technology (ICT) and digital innovation lead to dynamic changes in the business environment, where business transactions continue to shift from cash-based transactions to electronic-based transactions. The e-payment system was not introduced to replace cash but as a better alternative to cash and trade barter. Electronic payments can be understood as a payment mechanism using electronic media that does not involve cash. Electronic payment system (e-payment) is an important aspect of e-commerce. This study intends to review the available literature for e-payment systems on e-commerce with a view to highlighting the scope of the e-payment system, and the methodology used by previous researchers so as to identify research gaps and recommend for future studies.
Jasplakinolide's inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton.

BACKGROUND Jasplakinolide, a cyclodepsipeptide produced by an Indo-Pacific sponge, Jaspis johnstoni, has been reported to inhibit the growth of breast cancer cells. PURPOSE The effects of jasplakinolide on the proliferation of three human immortalized prostate carcinoma cell lines (PC-3, LNCaP, and TSU-Pr1) were studied. The growth-inhibitory effect of jasplakinolide on the PC-3 cell line was studied in detail to elucidate its mechanism of action. METHODS Cell counts were used to study growth inhibition. A protein-based microplate assay was used to assess the time of exposure needed to cause persistent growth inhibition and to study the effects of jasplakinolide analogues. Metabolic changes were assessed by following the incorporation of radiolabeled precursors. The effects of jasplakinolide on the cytoskeleton were studied by fluorescent microscopy, using rhodamine phalloidin (RP) and antibodies to cytoskeletal components. Changes in RP binding were quantified by extracting bound fluorescent material from fixed cells and measuring the amount of fluorescence in a spectrofluorometer. RESULTS The growth of PC-3, LNCaP, and TSU-Pr1 cells was potently inhibited by exposure to jasplakinolide for 48 hours; doses of jasplakinolide that led to 50% growth inhibition were 65 nM for PC-3 cells, 41 nM for LNCaP cells, and 170 nM for TSU-Pr1 cells. In PC-3 cells, exposure to 160 nM for 48 hours led to total growth inhibition, which persisted for several days even after drug removal. Several jasplakinolide analogues also inhibited the growth of PC-3 cells, although analogues in which the rigidity of the macrolide ring was altered were ineffective. No early changes in the synthesis of DNA, RNA, or protein or in intracellular adenosine triphosphate levels were seen in the PC-3 cells after exposure to jasplakinolide. Growth inhibition by jasplakinolide was accompanied by striking morphologic changes. Exposure for several doublings led to multinucleated cells. Further investigation of these changes in the PC-3 cells revealed a dramatic and early disruption of the actin cytoskeleton and a statistically significant decrease in RP binding. The doses of jasplakinolide, the time of exposure, and the pattern of growth inhibition by structural analogues corresponded with the changes seen in actin distribution. CONCLUSIONS Jasplakinolide represents a novel marine natural product with potent in vitro antiproliferative activity against human prostate carcinoma cell lines, and it appears to target the actin cytoskeleton. IMPLICATIONS Jasplakinolide is a potential candidate for further preclinical development and a lead structure for a novel class of therapeutic agents that can disrupt the actin cytoskeleton in mammalian cells.
Input-series common transformer connected PS-FB DC-DC converters for pulsed MIG welding

A pulsed Metal Inert Gas (PMIG) welding system is built based on the input-series common transformer connected phase-shifted full-bridge (PS-FB) DC/DC converters. Because the input-series connected converters share the same transformer magnetic core, equal sharing of input voltage can be achieved automatically without special voltage sharing control. To enhance the reliability of the system, a hybrid peak current control strategy consisting of arc length loop, average current loop and peak current loop is adopted. The system stability is analyzed based on the small signal model. The effectiveness of the proposed topology and its control strategy are verified by experimental results of a 15kW-50kHz welding machine.
Convertisseurs de forte puissance en commutation douce : association de structures "tout-silicium" à mécanismes de commutation duaux

Cette these traite de la caracterisation de nouvelles structures de convertisseurs de forte puissance fonctionnant en commutation douce. Ce mode de fonctionnement est obtenu sans elements reactifs, grâce a une association de convertisseurs (onduleur de tension et commutateur de courant) constitues d'interrupteurs a mecanismes de commutation duaux. La commutation douce permet notamment une meilleur surete de fonctionnement et une diminution considerable des pertes par commutation. Ces structures, qualifiees de tout-silicium, sont capables d'assurer une conversion continu-continu ou continu-alternatif. Elles peuvent tres bien se substituer aux systemes classiques de type hacheur et aux onduleurs MLI de forte puissance. Dans le cas d'un echange d'energie de type continu-alternatif, ces convertisseurs peuvent delivrer des courants quasi-sinusoidaux avec un facteur de deplacement unitaire. Par ailleurs, un autre avantage de ces structures reside dans une integration naturelle d'un isolement galvanique a la frequence de commutation des interrupteurs. Sur le meme principe, il est possible de realiser des structures multicellulaires. Celles-ci permettent une reduction appreciable des contraintes sur les interrupteurs et une amelioration des performances externes des convertisseurs. En outre, un choix judicieux de la frequence de commutation effectue au moyen d'une procedure de dimensionnement optimal conduit a une diminution de l'encombrement du transformateur d'isolement. Les structures permettant une conversion continu-continu ou continu-alternatif sont valides par des essais experimentaux sur une maquette de 50 kW controlee par un systeme numerique a DSP.
Gamma knife radiosurgery using 90 Gy for trigeminal neuralgia.

OBJECT The purpose of this paper was to assess the treatment of trigeminal neuralgia (TN) with the higher than normal dose of 90 Gy. METHODS Forty-two patients with typical TN were treated over a 3-year period with gamma knife radiosurgery. Every patient received a maximum dose of 90 Gy in a single 4-mm isocenter targeted to the root entry zone of the trigeminal nerve. Thirty of 42 patients had undergone no prior treatments. The median follow-up period was 14 months (range 2-30 months). Thirty-one patients (73.8%) achieved complete relief of pain. Nine patients (21.4%) obtained good pain control. Complications were limited to increased facial paresthesia in seven patients (16.7%) and dysgeusia in four patients (9.5%). CONCLUSIONS The authors conclude that the use of 90 Gy is a safe and effective dose for the treatment of TN.
New therapies in systemic lupus erythematosus.

A new understanding of the pathogenesis of autoimmunity, the mechanisms of action of older drugs, the advent of target-specific biological therapies and pharmacogenomics has created multiple treatment options for the patient with systemic lupus erythematosus. These include topical therapies, more selective non-steroidal anti-inflammatory agents, hormonal interventions and a new generation of immune suppressives. Currently available strategies also include the use of intravenous gamma globulin, apheresis, stem-cell transplantation and antileprosy preparations alone or in combination with immune suppressives. A handful of biologicals have been studied in clinical trials. After two decades without new options for lupus patients practitioners now have a full menu of improved therapeutic options.
DNA Lean Philosophy and TOC for Develop, Innovate and Improve Processes

EXPLORATORY RESEARCH. Analysis and review of fundamentals, principles, definitions and concepts around the DNA of the Lean Philosophy and Theory of Restrictions, to Develop, Innovate and Improve any Process.PROBLEM: How? Develop, Innovate and Improve Processes, applying the TPS - Toyota Production System and TOC for improvement and innovation in the management of the processes of the transformative and productive operations, in the creation and exchange of value and benefits.CONCLUSIONS:: Research exposed that the continuous improvement of all is achieved, focusing on improving the flow to increase the speed with which the system creates and delivers value, is the basis or the DNA of the TPS and TOC, for which it would be enough to identify the target value (truput) per unit of time that is creating the system, as well as what is the constraint (bottleneck or problem) that limits the capacity, to then develop innovations and improvements, which increase the trutput, applying the 4 principles followed by Ohno and the 5 steps of TOC.
Binary Mixtures of n-Alkanes for Tunable Thermohydraulic Microactuators

The two objectives of this paper are related to the use of n-alkanes in actuators. The first objective is to study the thermomechanics of binary mixtures of dotriacontane and hexatriacontane to see if a quasi-stable thermal expansion can be obtained, and the second one is to find the correspondence between dilatometry [pressure, volume, and temperature (pVT) measurement] and differential scanning calorimetry (DSC). Results show that there is indeed a concentration-dependent plateau in the expansion curves and that the width and horizontal position of this can be adjusted. As compared with pure n-alkanes, the plateaus of the mixtures widen by a factor of 2-4, and as compared with pure hexatriacontane, they shift their low-end temperatures by 5 to 10, in the 25% to 75% concentration range. The mixtures' plateaus (gathered around 0.06) are about 0.02 below those of the pure n-alkanes. It is shown that DSC can be used for a prediction of the thermomechanical properties of the substances, provided that a pVT reference exists, and the fact that the melting point increases with the pressure that is experienced with the dilatometer is considered. The qualitative similarity between the expansion and enthalpy curves is remarkable. About 25% to 30% of the total volume expansion is attributed to the solid-to-solid phase transition; the rest is attributed to thermal expansion and melting.
Two different Escherichia coli proP promoters respond to osmotic and growth phase signals

proP of Escherichia coli encodes an active transport system for proline and glycine betaine which is activated by both hyperosmolarity and amino acid-limited growth. proP DNA sequences far upstream from the translational start site are strongly homologous to the promoter of proU, an operon that specifies another osmoregulated glycine betaine transport system. Mutation and deletion analysis of proP and primer extension experiments established that this promoter, P1, was responsible for proP's strong expression in minimal medium and its response to osmotic signals. When cells were grown in complex medium, expression from a proP-lacZ fusion was induced three- to fourfold as growth slowed and cells entered stationary phase. Stationary-phase induction was dependent on rpoS, which encodes a stationary-phase sigma factor. Deletion of 158 bp of the untranslated leader sequence between P1 and the proP structural gene abolished rpoS-dependent stationary-phase regulation. Transcription initiation detected by primer extension within this region was absent in an rpoS mutant. proP is therefore a member of the growing class of sigma S-dependent genes which respond to both stationary-phase and hyperosmolarity signals.
Randomized, Double-Blind, Phase III Trial of Enzastaurin Versus Placebo in Patients Achieving Remission After First-Line Therapy for High-Risk Diffuse Large B-Cell Lymphoma.

PURPOSE To compare disease-free survival (DFS) after maintenance therapy with the selective protein kinase C β (PKCβ) inhibitor, enzastaurin, versus placebo in patients with diffuse large B-cell lymphoma (DLBCL) in complete remission and with a high risk of relapse after first-line therapy. PATIENTS AND METHODS This multicenter, phase III, randomized, double-blind, placebo-controlled trial enrolled patients who were at high risk of recurrence after rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients (N = 758) with stage II bulky or stage III to IV DLBCL, three or more International Prognostic Index risk factors at diagnosis, and a complete response or unconfirmed complete response after 6 to 8 cycles of R-CHOP were assigned 2:1 to receive oral enzastaurin 500 mg daily or placebo for 3 years or until disease progression or unacceptable toxicity. Primary end point was DFS 3 years after the last patient entered treatment. Correlative analyses of biomarkers, including cell of origin by immunohistochemistry and PKCβ expression, with efficacy outcomes were exploratory objectives. RESULTS After a median follow-up of 48 months, DFS hazard ratio for enzastaurin versus placebo was 0.92 (95% CI, 0.689 to 1.216; two-sided log-rank P = .541; 4-year DFS, 70% v 71%, respectively). Independent of treatment, no significant associations were observed between PKCβ protein expression or cell of origin and DFS or overall survival. CONCLUSION Enzastaurin did not significantly improve DFS in patients with high-risk DLBCL after achieving complete response to R-CHOP. Achievement of a complete response may have abrogated the prognostic significance of cell of origin by immunohistochemistry.