Miracle-dz/UniFAR-FTUs huggingface dataset:
The Antioxidant Transcription Factor Nrf2 Negatively Regulates Autophagy and Growth Arrest Induced by the Anticancer Redox Agent Mitoquinone*

Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ treatment led to irreversible inhibition of clonogenic growth of breast cancer cells through a combination of autophagy and apoptotic cell death mechanisms. Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme Q10. Inhibition of cancer cell growth by MitoQ was associated with G1/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The possible role of oxidative stress in MitoQ activity was investigated by measuring the products of hydroethidine oxidation. Increases in ethidium and dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2 protein levels, nuclear localization, and transcriptional activity also increased following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in autophagy and an increase in G1 cell cycle arrest in response to MitoQ but had no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity.
Runaway Dendrites: Blame the Older Siblings

Commentary Temporal lobe epilepsy (TLE) is one of the most common intractable epilepsy syndromes encountered in the clinic. Hippocampal pathology in TLE patients includes loss of hilar cells and pyramidal neurons in CA1 and CA3, astroand microgliosis, and architectural abnormalities of the dentate granule cells (DGCs). The latter comprises three main structural alterations. First is an abnormal localization of the DGC soma, resulting in dispersion of the granule cell layer and hilar ectopic DGCs. Second, the axonal projections of DGCs (termed “mossy fibers”) remodel abnormally as well, resulting in mossy fiber sprouting into the dentate inner molecular layer, where DGCs normally receive synaptic inputs (1). Third, many DGCs exhibit abnormal dendritic trees with dendrites projecting into the hilus; these are known as hilar basal dendrites (HBDs) (2, 3). Multiple animal models of TLE exist. These models are typically created by local or systemic administration of chemicals, toxins, or electrical stimulation to induce status epilepticus (4). Although they differ in the degree to which they recapitulate the aforementioned neuropathologic abnormalities, the presence of mossy-fiber sprouting seems to be a constant finding (5). The presence of HBDs, however, has only been examined and identified in a subset of TLE models to date, including those involving intraperitoneal application of either kainic acid (KA) or pilocarpine (2, 3). Of interest, in both of these animal models, the induction of epilepsy markedly increases DGC neurogenesis (6). Furthermore, only DGCs maturing during, or especially those generated after, the epileptogenic insult exhibit persistent HBDs (7–9). The study by Murphy et al. aims to investigate whether HBDs might be present in the only known adult rodent model Abnormalities of Granule Cell Dendritic Structure Are a Prominent Feature of the Intrahippocampal Kainic Acid Model of Epilepsy Despite Reduced Postinjury Neurogenesis.
[Psychiatric and cognitive complications arising from subthalamic stimulation in Parkinson's disease].

INTRODUCTION AND DEVELOPMENT Subthalamic stimulation is a therapeutic option that can be used to treat advanced cases of Parkinson's disease. However, psychiatric or cognitive disorders have been reported in some patients treated using this technique. Age and a long disease history are two important risk factors for the appearance of these problems. The complications that have been reported include cases of depression, apathy, manias and psychosis. Surgery can also exacerbate the syndrome of addiction to levodopa that is sometimes observed. In contrast, sleep disorders usually improve with this technique. As far as the cognitive sphere is concerned, verbal fluency has been seen to deteriorate and the executive functions become impaired in patients over 69 years of age. These disorders are usually due to a number of different causes and have been attributed to the action of stimulating areas close to the subthalamic nucleus, to the presence of previously existing cognitive or psychiatric problems, to unrealistic expectations about this technique or to the individual's inability to adapt to the functional situation after surgery. CONCLUSIONS Although generally speaking these disorders are not usually serious, they must be borne in mind so that adequate treatment can be indicated.
The dose uptake ratio as an index of glucose metabolism: useful parameter or oversimplification?

UNLABELLED The dose uptake ratio (DUR) has been used as a quantitative index of glucose metabolism for tumor classification and monitoring response to treatment. In order to provide consistent results, DUR measurements should be made when the concentration of tracer has reached a plateau. The time of this plateau cannot be identified from a single static acquisition. METHODS In this study, we investigated the changes in DUR as a function of time in eight patients with stage III lung cancer. All patients underwent a quantitative dynamic 18F-FDG PET study before and after treatment and the data were analyzed with a three-compartment model. Using the fitted model parameters, the DUR was predicted at the plateau and intermediate times. RESULTS Tumor concentrations of 18F-FDG did not reach a plateau within the 90 min of imaging in any of the pre-treatment studies and only in one case post-treatment. The average time to reach 95% of the plateau value pre-treatment was 298 +/- 42 min (range: 130-500 min); in post-treatment, it was 154 +/- 31 min (range: 65-240 min). The difference between the plateau DUR and the 60-min value was 46% +/- 6% pre-treatment and 17% +/- 5% post-treatment. CONCLUSIONS These data indicate that DUR can vary widely with the time of measurement and that DUR should be interpreted with caution in any individual patient.
RELATIONSHIP BETWEEN CHOLINE AVAILABILITY AND ACETYLCHOLINE SYNTHESIS IN DISCRETE REGIONS OF RAT BRAIN

Abstract— The relationship between choline availability and the synthesis of acetylcholine in discrete brain regions was studied in animals treated with the organophosphorus cholinesterase inhibitor paraoxon. Administration of paraoxon (0.23 mg/kg) inhibited acetylcholinesterase activity by approx 90% in the striatum, hippocampus and cerebral cortex and increased acetylcholine levels to 149%, 124% and 152% of control values, respectively. Free choline levels were unaltered by paraoxon in the hippocampus and cerebral cortex, but were significantly decreased in the striatum to 74% of control. When animals were injected with choline chloride (60 mg/kg), 60 min prior to the administration of paraoxon, the paraoxon‐induced choline depletion in the striatum was prevented and the paraoxon‐induced acetylcholine increase was potentiated from 149% to 177% of control values. Choline pretreatment had no significant effect in either the hippocampus or cerebral cortex, brain regions that did not exhibit a decrease in free choline levels after paraoxon administration. Results indicate that choline administration, which had no significant effect on acetylcholine levels by itself, increased acetylcholine synthesis in the striatum in the presence of acetylcholinesterase inhibition. However, this effect was not apparent in either the hippocampus or the cerebral cortex at similar levels of enzyme inhibition. It appears that choline generated from the hydrolysis of acetylcholine may play a significant role in the regulation of neurotransmitter synthesis in the striatum, but not in the other brain areas studied. The evidence supports the concept that the regulatory mechanisms controlling the synthesis of acetylcholine in striatal interneurons may differ from those in other brain regions.
Ecology of parasite-vector interactions

Vector-borne diseases continue to be one of the most important determinants affecting human and animal health. Large numbers of people suffer from diseases like malaria, dengue, filariasis and leishmaniasis, especially in the tropics. Whereas these diseases were eradicated from the temperate climate zones, in recent years the rising incidence of 'emerging' vector-borne diseases such as bluetongue, West Nile Virus, Lyme disease, tick-borne encephalitis and the recent outbreaks of chikungunya and dengue in southern Europe provide evidence that these diseases are resilient and can disperse to other regions and continents where before they were not present or relevant. Many tools for the management of vector-borne diseases are currently under pressure because of increasing drug and insecticide resistance, as well as the realization of biological variation of parasites and vectors and their ecosystems. At the same time, progress in our understanding of genetics, immunology, population biology and epidemiology allow for a better understanding of parasite-vector interactions. Here the state-of-the-art of these interactions is being reviewed, and means for using this information for advanced strategies of vector-borne disease control are proposed. This 3rd edition of ECVD aims to provide a rapid overview of recent developments in the field of parasite-vector interactions and how this can be used for more effective and sustainable disease control.
The effect of total sleep deprivation on plasma melatonin and cortisol in healthy human volunteers.

Twelve healthy volunteers were included in this study. Baseline curves for melatonin and cortisol were obtained after one night of adaptation to laboratory conditions. From 10:00 p.m. to 6:00 a.m., blood samples were drawn every hour. On the third night, the subjects were kept awake at the sleep unit. Curves for the two hormones were then obtained after 36 h of total sleep deprivation (SD). The levels of these hormones were evaluated by calculating the area under the curve at each hour in both situations (basal and after sleep deprivation). It was found that the melatonin levels were increased after sleep deprivation, whereas the cortisol levels remained the same. These results suggest a mechanism by which a reset of abnormal rhythms can occur in depression.
FREE AMINO ACIDS IN DEVELOPING RAT RETINA

—During postnatal growth the free amino acids pattern of rat retina differs at various developmental stages. The adult level for individual amino acids is reached on the 30th day of maturation. During differentiation the taurine, glutamic acid, GABA, glutamine, aspartic acid, glycine arginine, methionine and histidine levels increase while proline. alanine, ornithine and tyrosine decrease.
In Silico Mapping of Complex Disease-Related Traits in Mice

Experimental murine genetic models of complex human disease show great potential for understanding human disease pathogenesis. To reduce the time required for analysis of such models from many months down to milliseconds, a computational method for predicting chromosomal regions regulating phenotypic traits and a murine database of single nucleotide polymorphisms were developed. After entry of phenotypic information obtained from inbred mouse strains, the phenotypic and genotypic information is analyzed in silico to predict the chromosomal regions regulating the phenotypic trait.
Mutant Prevention Concentrations of Levofloxacin Alone and in Combination with Azithromycin, Ceftazidime, Colistin (Polymyxin E), Meropenem, Piperacillin-Tazobactam, and Tobramycin against Pseudomonas aeruginosa

ABSTRACT The mutant prevention concentrations (MPCs) of levofloxacin alone and in combination with ceftazidime, colistin (polymyxin E), meropenem, piperacillin-tazobactam, and tobramycin were established against Pseudomonas aeruginosa. Antibiotic combinations using levofloxacin with any antibiotic with individual activity against P. aeruginosa resulted in synergistic lowering (an at-least-fourfold reduction) of the isolate's MPC.
Optimization of word alignment clues

Statistical, linguistic, and heuristic clues can be used for the alignment of words and multi-word units in parallel texts. This article describes the clue alignment approach and the optimization of its parameters using a genetic algorithm. Word alignment clues can come from various sources such as statistical alignment models, co-occurrence tests, string similarity scores and static dictionaries. A genetic algorithm implementing an evolutionary procedure can be used to optimize the parameters necessary for combining available clues. Experiments on English/Swedish bitext show a significant improvement of about 6% in F-scores compared to the baseline produced by statistical word alignment.Most of the work described in this paper was carried out at the Department of Linguistics and Philology at Uppsala University. I would like to acknowledge technical and scientific support by people at the department in Uppsala.
LEAKAGE POWER REDUCTION IN CMOS CIRCUITS USING LEAKAGE CONTROL TRANSISTOR TECHNIQUE IN NANOSCALE TECHNOLOGY

In this paper, we propose a leakage reduction technique. Because high leakage currents in deep submicron regimes are becoming a major contributor to total power dissipation of CMOS circuits. Sub threshold leakage current plays a very important role in power dissipation. So to reduce the sub threshold leakage current we proposed an adaptive voltage level (AVL) technique. Which optimize the overall voltage across the half subtractor circuit in active mode. In this AVL technique, Two schemes are employed, one is AVLS (adaptive voltage level at supply) in which the supply voltage is reduced and the other is AVLG (adaptive voltage level at ground) in which the ground potential is increased. By applying this technique we have reduced the leakage current from 9.274pa to 5.428. That means this technique the leakage current 41.4% . the circuit is simulated on cadence virtuoso in 45nm CMOS technology. Simulation results revealed that there is a significant reduction in leakage current for this proposed cell with the AVL circuit reducing the supply voltage.
Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis

Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34+ progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. (Clinicaltrials.gov identifier: NCT00044122, NCT00001756)
Fear of InjuryWith Physical Activity Is Greater in AdultsWith Diabetes Than in AdultsWithout Diabetes

OBJECTIVE—Physical activity is a cornerstone of treatment for diabetes, yet people with diabetes perform less moderate and vigorous physical activity (MVPA) than people without diabetes. In contrast, whether differences in walking activity exist has been understudied. Diabetes-specific barriers to physical activity are one possible explanation for lower MVPA in diabetes. We hypothesized that people with diabetes would perform less walking and combined MVPA and would be less likely to anticipate increasing physical activity if barriers were theoretically absent compared with people without diabetes.
[Advances in pulmonology in year 2012].

Joanna Chorostowska-Wynimko, Urszula Demkow, Paweł Górski, Katarzyna Krenke, Marcin Kurzyna, Jan Kuś, Renata Langfort, Krystyna Maszkowska-Kopij, Kazimierz Roszkowski-Śliż, Wojciech Skorupa, Agnieszka Sobczyńska-Tomaszewska, Małgorzata Szołkowska, Adam Torbicki Samodzielna Pracownia Diagnostyki Molekularnej i Immunologii, Instytut Gruźlicy i Chorób Płuc w Warszawie Zakład Diagnostyki Laboratoryjnej i Immunologii Klinicznej Wieku Rozwojowego Warszawskiego Uniwersytetu Medycznego Klinika Pneumonologii i Alergologii I Katedry Chorób Wewnętrznych Uniwersytetu Medycznego w Łodzi Klinika Pneumonologii i Alergologii Wieku Dziecięcego Warszawskiego Uniwersytetu Medycznego Klinika Krążenia Płucnego i Chorób Zakrzepowo-Zatorowych Centrum Medycznego Kształcenia Podyplomowego, Europejskie Centrum Zdrowia w Otwocku I Klinika Chorób Płuc Instytutu Gruźlicy i Chorób Płuc w Warszawie Zakład Patomorfologii Instytutu Gr uźlicy i Chorób Płuc w Warszawie Przychodnia Przykliniczna Instytutu Gruźlicy i Chorób Płuc w Warszawie III Klinika Chorób Płuc Instytutu Gruźlicy i Chorób Płuc w Warszawie Medgen w Warszawie
Oral treatment with the melatonin agonist agomelatine lowers the intraocular pressure of glaucoma patients

Agomelatine is an agonist of melatonin that is used in the treatment of major depressive disorders. It has also shown an ability to decrease IOP in experiment animals and in normal human subjects. This pilot study addresses for the first time agomelatine effects on the IOP of patients affected by POAG.
The dMi‐2 chromodomains are DNA binding modules important for ATP‐dependent nucleosome mobilization

Drosophila Mi‐2 (dMi‐2) is the ATPase subunit of a complex combining ATP‐dependent nucleosome remodelling and histone deacetylase activities. dMi‐2 contains an HMG box‐like region, two PHD fingers, two chromodomains and a SNF2‐type ATPase domain. It is not known which of these domains contribute to nucleosome remodelling. We have tested a panel of dMi‐2 deletion mutants in ATPase, nucleosome mobilization and nucleosome binding assays. Deletion of the chromodomains impairs all three activities. A dMi‐2 mutant lacking the chromodomains is incorporated into a functional histone deacetylase complex in vivo but has lost nucleosome‐stimulated ATPase activity. In contrast to dHP1, dMi‐2 does not bind methylated histone H3 tails and does not require histone tails for nucleosome binding. Instead, the dMi‐2 chromodomains display DNA binding activity that is not shared by other chromodomains. Our results suggest that the chromodomains act at an early step of the remodelling process to bind the nucleosome substrate predominantly via protein–DNA interactions. Furthermore, we identify DNA binding as a novel chromodomain‐associated activity.
Assessment of energy expenditure in overweight women.

PURPOSE To compare field measures of average daily energy expenditure (ADEE) against criterion data by the doubly labeled water method (DLW) in overweight women. METHODS The subject were 20 overweight (BMI 29.9 +a- 3.0 kg.m-2) premenopausal women. Energy expenditure was measured by DLW and by the factorial method (activity diary, two techniques differing by method to obtain resting energy expenditure, REE), heart-rate monitoring (HR, two techniques differing by the FLEX-point to discriminate sedentary and activity HR), accelerometer, and pedometer. RESULTS The ADEE(DLW) was 10.26 +a- 1.1 MJ.d-1. The mean bias (ADEE by the alternative minus ADEE(DLW) was smallest for the accelerometer (+ 0.08 +a- 1.63 MJ) and HR-FLEX10 (+ 0.11 +a- 1.67 MJ). The HR-FLEX(0) technique (lower FLEX-point) overestimated ADEE by + 1.18 (+a- 1.97 MJ). However, the random error (SD of bias) was smaller for both factorial techniques (REE measured: -0.48 +2- 0.81 MJ; REE calculated from the WHO equation: -0.22 +2- 0.88 MJ). CONCLUSION The results show that simple factorial methods may assess ADEE with small random errors in population with a rather narrow range of physical activity. The accelerometer and HR with the higher FLEX-point have comparable results with smaller bias but larger random error compared with the factorial techniques.
Automatic modulation classification algorithm using higher-order cumulants under real-world channel conditions

An automatic modulation classification algorithm for application in communications via multipath fading channels, without a priori information on channel characteristics, based on normalized sixth-order cumulants is described. In comparison with existing approaches, proposed algorithm can achieve much better classification accuracy in distinguishing BPSK from complex-valued modulation techniques. Theoretical analysis is verified via extensive simulations, under real-world channel propagation conditions.
Early disturbances in cardiorespiratory control

Early disturbances in cardiorespiratory control can manifest as apnea of prematurity, acute life-threatening events (ALTE) or sudden infant death syndrome (SIDS), and congenital central hypoventilation (CCHV) syndrome. The main clinical and functional characteristics of early cardiorespiratory control disturbances are briefly reviewed in this article. Current hypotheses suggesting a shared mechanism for these disturbances are discussed.
Towards exploratory faceted search systems

Towards Exploratory Faceted Search Systems Alex Ksikes In this thesis, we cover what we believe would be the main ingredients of an exploratory search system (ESS). In a nutshell, these are textual queries, facets, visual results, social search and query-by-example. The goal of the thesis is to show how all of these elements could readily be integrated into a typical faceted search system that users are already accustomed to. In this respect, we propose that the future of exploratory search might be a traditional faceted search system, but with the added ingredients of information visualizations and query-by-example. To illustrate our ideas we have built two freely available web applications. The first one, Biomed Search, has been positively received by the community and o↵ers some novel characteristics. First, in order to improve on both precision and recall, Biomed Search indexes not only the text caption but also the text that refers to the image. Second, the interface uses a common pattern of zooming in on a particular search result in order to display more information. User feedback on Biomed Search has hinted towards faceted search, visual search results and query-by-example. The second system, Cloud Mining, is an attempt at implementing the vision set forth in this thesis. The system is a framework used to instantiate ESSs. It o↵ers the novel characteristics of facet views as well as multiple-item based searches combined with textual queries. Cloud Mining paves the way to a completely pluggable search framework, in which every component would be driven by a community of users. The system was tested on large publicly available datasets and all its software components are available under an open source license. The main contributions of this thesis come as lessons learned, suggestions or recommendations as to how to extend the current paradigm of faceted search into the one of exploratory search. The search results and facets should be extended with di↵erent views. Query by example should be integrated with Bayesian Sets as it reduces the handling of complex content based searches to choosing the right plugin. Finally, the system should be thought as a framework to instantiate ESSs, in which every one of its component is a community driven plugin. These customized tailored tools, when applied to a dataset of interest, could o↵er a collective intelligence approach to information overload.