Miracle-dz/UniFAR-FTUs huggingface dataset:
Asiatic Acid, a Triterpene, Induces Apoptosis and Cell Cycle Arrest through Activation of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways in Human Breast Cancer Cells

This study first investigates the anticancer effect of asiatic acid in two human breast cancer cell lines, MCF-7 and MDA-MB-231. Asiatic acid exhibited effective cell growth inhibition by inducing cancer cells to undergo S-G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels and reduced amounts of cyclinB1, cyclinA, Cdc2, and Cdc25C in a p53-independent manner. Asiatic acid also reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and the level of inactivated phospho-Cdc2 and phospho-Cdc25C. Asiatic acid treatment triggered the mitochondrial apoptotic pathway indicated by changing Bax/Bcl-2 ratios, cytochrome c release, and caspase-9 activation, but it did not act on Fas/Fas ligand pathways and the activation of caspase-8. We also found that mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2), and p38, but not c-Jun NH2-terminal kinase (JNK), are critical mediators in asiatic acid-induced cell growth inhibition. U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] or SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole], specific inhibitors of mitogen-activated protein kinase kinase and p38 kinase activities, significantly decreased or delayed apoptosis. Asiatic acid was likely to confine the breast cancer cells in the S-G2/M phase mainly through the p38 pathway, because both SB203580 and p38 small interfering RNA (siRNA) inhibition significantly attenuated the accumulation of inactive phospho-Cdc2 and phospho-Cdc25C proteins and the cell numbers of S-G2/M phase. Moreover, U0126 and ERK siRNA inhibition completely suppressed asiatic acid-induced Bcl-2 phosphorylation and Bax up-regulation, and caspase-9 activation. Together, these results imply a critical role for ERK1/2 and p38 but not JNK, p53, and Fas/Fas ligand in asiatic acid-induced S-G2/M arrest and apoptosis of human breast cancer cells.
Methods for Ripple Index evaluation in DC Low Voltage Distribution Networks

Power quality indices for ripple evaluation in DC low voltage networks are presented and discussed. Ripple is interpreted in a more general way than a simple periodic fluctuation of network voltage due to rectifying harmonics: the indices are conceived to cope with PQ definition of several standards in terms of frequency range and related phenomena. The proposed PQ indices are implemented for real-time execution; performances are evaluated in Matlab.
Targeting the PI3K Pathway in the Brain—Efficacy of a PI3K Inhibitor Optimized to Cross the Blood–Brain Barrier

Purpose: Glioblastoma (GBM), the most common primary brain tumor in adults, presents a high frequency of alteration in the PI3K pathway. Our objectives were to identify a dual PI3K/mTOR inhibitor optimized to cross the blood–brain barrier (BBB) and characterize its brain penetration, pathway modulation in the brain and efficacy in orthotopic xenograft models of GBM. Experimental Design: Physicochemical properties of PI3K inhibitors were optimized using in silico tools, leading to the identification of GNE-317. This compound was tested in cells overexpressing P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP). Following administration to mice, GNE-317 plasma and brain concentrations were determined, and phosphorylated biomarkers (pAkt, p4EBP1, and pS6) were measured to assess PI3K pathway suppression in the brain. GNE-317 efficacy was evaluated in the U87, GS2, and GBM10 orthotopic models of GBM. Results: GNE-317 was identified as having physicochemical properties predictive of low efflux by P-gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic models, achieving tumor growth inhibition of 90% and 50%, and survival benefit, respectively. Conclusions: These results indicated that specific optimization of PI3K inhibitors to cross the BBB led to potent suppression of the PI3K pathway in healthy brain. The efficacy of GNE-317 in 3 intracranial models of GBM suggested that this compound could be effective in the treatment of GBM. Clin Cancer Res; 18(22); 6239–48. ©2012 AACR.
The Many lives of AGN: Cooling flows, black holes and the luminosities and colours of galaxies

We simulate the growth of galaxies and their central supermassive black holes by implementing a suite of semi-analytic models on the output of the Millennium Run, a very large simulation of the concordanceCDM cosmogony. Our procedures fol- low the detailed assembly history of each object and are able to track the evolution of all galaxies more massive than the Small Magellanic Cloud throughout a volume comparable to that of large modern redshift surveys. In this first paper we supple- ment previous treatments of the growth and activity of central black holes with a new model for 'radio' feedback from those AGN that lie at the centre of a quasistatic X-ray emitting atmosphere in a galaxy group or cluster. We show that for energetically and observationally plausible parameters such a model can simultaneously explain: (i) the low observed mass drop-out rate in cooling flows; (ii) the exponential cut-off at the bright end of the galaxy luminosity function; and (iii) the fact that the most massive galaxies tend to be bulge-dominated systems in clusters and to contain systematically older stars than lower mass galaxies. This success occurs because static hot atmo- spheres form only in the most massive structures, and radio feedback (in contrast, for example, to supernova or starburst feedback) can suppress further cooling and star formation without itself requiring star formation. We discuss possible physical mod- els which might explain the accretion rate scalings required for our phenomenological 'radio mode' model to be successful.
Effect of the Extracts of the Spiderflower, Cleome arabica, on Feeding and Survival of Larvae of the Cotton Leafworm, Spodoptera littoralis

Abstract Aqueous and organic (hexane, chloroform, and methanol) extracts of siliquae, stems and leaves, and seeds of Cleome arabica L. (Brassicales: Capparidaceae) were evaluated in the laboratory for their antifeeding and insecticidal effect on larvae of the cotton leafworm, Spodoptera littoralis (Boisduval) (Lepidoptera, Noctuidae), using a leaf dipping bioassay with castor bean, Ricinus communis L. (Malpighiales: Euphorbiaceae), leaf discs. The polar extracts caused significant mortality. At the highest dose, C. arabica extracts exhibited significant antifeeding and phagostimulating activities against S. littoralis larvae. Under no-choice conditions, the methanol extract of siliquae was the most active, and the antifeedant index calculated over 24 hr for 3rd instar larvae varied significantly from 16 to 37%. Using nutritional indices, it was established that there was a significant decrease in growth rate concomitant with a reduction in consumption. These results suggest the presence of anti-feeding and/or toxic substances in the extracts that may be useful in developing bio-insecticides based on C. arabica extracts for use in integrated pest management of leafworm and other agricultural pests.
Supersolar Super-Lyman Limit Systems

We present abundance measurements for two super-Lyman limit systems (SLLSs; quasar absorption-line systems with 1019 cm-2 < N < 1020.3 cm-2) selected from a set of metal-strong absorbers in the SDSS quasar database. After applying estimate corrections for photoionization effects, we derive gas-phase metallicities of [M/H] = +0.7 ± 0.2 dex for the SLLS at z = 1.7749 toward SDSS 0927+5621 and [M/H] = +0.05 ± 0.1 dex for the SLLS at z = 1.7678 toward SDSS 0953+5230. The former exhibits one of the highest gas metallicities of any astrophysical environment, and its total metal surface density exceeds that of nearly every known damped Lyα system. The properties of these absorbers—high metallicity and large velocity width (Δv > 300 km s-1)—resemble those of gas observed in absorption in the spectra of bright, star-forming galaxies at high redshift. We discuss the metal mass density of the SLLSs based on these observations and our SLLS survey, and we argue that a conservative estimate to the total metal budget at z = 2 is greater than 15% of the total, suggesting that metal-rich LLSs may represent the dominant metal reservoir in the young universe.
Graded Blood Pressure Reduction in Hypertensive Outpatients Associated With Use of a Device to Assist With Slow Breathing

To study the effects of device‐guided breathing on office systolic blood pressure (SBP), five centers randomized 149 untrained hypertensives (50% male, age 59±10 years, baseline blood pressure 150±9/86±9 mm Hg, 77% taking drug therapy). One half received a device to guide slow breathing; all received a home blood pressure monitor and only simple, written instructions. The changes in office SBP (adjusted for office‐to‐home difference in baseline SBP and accumulated time spent in slow breathing, guided and measured by the device) were significantly (p<0.001 for trend) correlated with accumulated time spent in slow breathing. Greater decreases in SBP (−15.0±1.8 vs. −7.3±1.9 mm Hg) were observed for those who spent more (vs. less) than 180 minutes over 8 weeks in slow breathing, as well as those who just monitored their blood pressure at home (−9.2±1.6 mm Hg). Thus, even without training, hypertensive patients who receive a device to guide slow breathing significantly lowered their office SBP if the total time spent in slow breathing over 8 weeks exceeded a "threshold" value of 180 minutes.
Observational Learning in Large Anonymous Games

I present a model of observational learning with payoff interdependence. Agents, ordered in a sequence, receive private signals about an uncertain state of the world and sample previous actions. Unlike in standard models of observational learning, an agent’s payoff depends both on the state and on the actions of others. Agents want both to learn the state and to anticipate others’ play. As the sample of previous actions provides information on both dimensions, standard informational externalities are confounded with payoff externalities. I show that in spite of these confounding factors, when signals are of unbounded strength, there is learning in a strong sense: agents’ actions are ex post optimal given both the state of the world and others’ actions. With bounded signals, actions approach ex post optimality as the signal structure becomes more informative.
Effect of Pacing the Right Ventricular Mid‐Septum Tract in Patients with Permanent Atrial Fibrillation and Low Ejection Fraction

Introduction: Permanent right ventricular (RV) pacing leads have been traditionally implanted in the right ventricular apex (RVA). Nowadays, some deleterious effects of RVA pacing have been recognized. The aim of this study was to evaluate the effect of different sites of RV pacing in patients with permanent atrial fibrillation (AF) and low ejection fraction (LEF) needing a pacemaker (PM) implantation.
On joint distribution of adjacencies, descents and some Mahonian statistics

We prove several conjectures of Eriksen regarding the joint distribution on permutations of the number of adjacencies (descents with consecutive values in consecutive positions), descents and some Mahonian statistics. We also prove Eriksen's conjecture that a certain bistatistic on Viennot's alternative tableaux is Euler-Mahonian.
Low complexity word-level sequential normal basis multipliers

For efficient hardware implementation of finite field arithmetic units, the use of a normal basis is advantageous. In this paper, two classes of architectures for multipliers over the finite field GF(2/sup m/) are proposed. These multipliers are of sequential type, i.e., after receiving the coordinates of the two input field elements, they go through k, 1 /spl les/ k /spl les/ m, iterations (i.e., clock cycles) to finally yield all the coordinates of the product in parallel. The value of k depends on the word size w = /spl lceil/m/k/spl rceil/. For w > 1, these multipliers are highly area efficient and require fewer number of logic gates even when compared with the most area efficient multipliers available in the open literature. This makes the proposed multipliers suitable for applications where the value of m is large but space is of concern, e.g., resource constrained cryptographic systems. Additionally, if the field dimension m is composite, i.e., m = kn, then the extension of one class of the architectures yields a highly efficient multiplier over composite fields.
Combinatorial interactions of Serpent, Lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis

The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte production, respectively. In contrast U-shaped, a Friend of GATA class factor, antagonizes crystal cell formation. Here we show that Srp, Lozenge, and U-shaped interact in different combinations to regulate crystal cell lineage commitment. Coexpression of Srp and Lozenge synergistically activated the crystal cell program in both embryonic and larval stages. Furthermore, expression of Lozenge and SrpNC, a Srp isoform with N- and C-terminal zinc fingers, inhibited u-shaped expression, indicating that crystal cell activation coincided with the down-regulation of this repressor-encoding gene. In contrast, whereas U-shaped and SrpNC together blocked crystal cell production, coexpression of U-shaped with noninteracting Srp proteins failed to prevent overproduction of this hemocyte population. Such results indicated that U-shaped and SrpNC must interact to block crystal cell production. Taken together, these studies show that the specialized SrpNC isoform plays a pivotal role during crystal cell lineage commitment, acting as an activator or repressor depending on the availability of specific transcriptional coregulators. These findings provide definitive proof of the combinatorial regulation of hematopoiesis in Drosophila and an in vivo demonstration of GATA and Runx functional interaction in a blood cell commitment program.
The Ins and Outs of Small GTPase Rac1 in the Vasculature

The Rho family of small GTPases forms a 20-member family within the Ras superfamily of GTP-dependent enzymes that are activated by a variety of extracellular signals. The most well known Rho family members are RhoA (Ras homolog gene family, member A), Cdc42 (cell division control protein 42), and Rac1 (Ras-related C3 botulinum toxin substrate 1), which affect intracellular signaling pathways that regulate a plethora of critical cellular functions, such as oxidative stress, cellular contacts, migration, and proliferation. In this review, we describe the current knowledge on the role of GTPase Rac1 in the vasculature. Whereas most recent reviews focus on the role of vascular Rac1 in endothelial cells, in the present review we also highlight the functional involvement of Rac1 in other vascular cells types, namely, smooth muscle cells present in the media and fibroblasts located in the adventitia of the vessel wall. Collectively, this overview shows that Rac1 activity is involved in various functions within one cell type at distinct locations within the cell, and that there are overlapping but also cell type–specific functions in the vasculature. Chronically enhanced Rac1 activity seems to contribute to vascular pathology; however, Rac1 is essential to vascular homeostasis, which makes Rac1 inhibition as a therapeutic option a delicate balancing act.
Mental Illness Detection at the World Well-Being Project for the CLPsych 2015 Shared Task

This article is a system description and report on the submission of the World Well-Being Project from the University of Pennsylvania in the ‘CLPsych 2015’ shared task. The goal of the shared task was to automatically determine Twitter users who self-reported having one of two mental illnesses: post traumatic stress disorder (PTSD) and depression. Our system employs user metadata and textual features derived from Twitter posts. To reduce the feature space and avoid data sparsity, we consider several word clustering approaches. We explore the use of linear classifiers based on different feature sets as well as a combination use a linear ensemble. This method is agnostic of illness specific features, such as lists of medicines, thus making it readily applicable in other scenarios. Our approach ranked second in all tasks on average precision and showed best results at . 1 false positive rates.
Effect of reinforcement percentage of eucalyptus fibers on physico-mechanical properties of composite hand lay-up with polyester thermosetting matrix

ABSTRACT With the aim to produce more sustainable materials, the scientific community seeks alternatives to replace raw materials from nonrenewable sources. We evaluated the influence of inclusion at different levels of Eucalyptus grandis × Eucalyptus urophylla fibers on the physico-mechanical properties of polymer composites. Unsaturated orthophthalic polyester resin was applied. Fibers were used at following concentrations: 0, 5, 10, 15, 20, 25 and 30 wt%. Composites were evaluated in terms of to their microstructure and their mechanical and physical properties. Twenty five percent reinforcement was more suitable for composites’ production, without predominantly effect on their properties.
Nucleotide Excision Repair and Vitamin D—Relevance for Skin Cancer Therapy

Ultraviolet (UV) radiation is involved in almost all skin cancer cases, but on the other hand, it stimulates the production of pre-vitamin D3, whose active metabolite, 1,25-dihydroxyvitamin D3 (1,25VD3), plays important physiological functions on binding with its receptor (vitamin D receptor, VDR). UV-induced DNA damages in the form of cyclobutane pyrimidine dimers or (6-4)-pyrimidine-pyrimidone photoproducts are frequently found in skin cancer and its precursors. Therefore, removing these lesions is essential for the prevention of skin cancer. As UV-induced DNA damages are repaired by nucleotide excision repair (NER), the interaction of 1,25VD3 with NER components can be important for skin cancer transformation. Several studies show that 1,25VD3 protects DNA against damage induced by UV, but the exact mechanism of this protection is not completely clear. 1,25VD3 was also shown to affect cell cycle regulation and apoptosis in several signaling pathways, so it can be considered as a potential modulator of the cellular DNA damage response, which is crucial for mutagenesis and cancer transformation. 1,25VD3 was shown to affect DNA repair and potentially NER through decreasing nitrosylation of DNA repair enzymes by NO overproduction by UV, but other mechanisms of the interaction between 1,25VD3 and NER machinery also are suggested. Therefore, the array of NER gene functioning could be analyzed and an appropriate amount of 1.25VD3 could be recommended to decrease UV-induced DNA damage important for skin cancer transformation.
A Novel Approach of Optimum Multi-criteria Vertical Handoff Algorithm for Heterogeneous Wireless Networks

In this paper is proposed method of intellectual vertical handover that allows performing unloading of wireless heterogeneous access networks using multi-criteria network evaluation. An algorithm of handover functioning is further improved using fuzzy logic based on cloud technology. An imitation model is created for investigation of heterogeneous network with realization of proposed algorithm of initiation of vertical handover. A process of service provisioning by heterogeneous network is investigated based on created model. In the process of modeling it is shown that proposed algorithm allows choosing optimal cell for each individual user among available cells of different access systems.
Stereotactic radiotherapy of the prostate: fractionation and utilization in the United States

Purpose To analyze the utilization and fractionation of extreme hypofractionation via stereotactic body radiotherapy (SBRT) in the treatment of prostate cancer. Materials and Methods Data was analyzed on men diagnosed with localized prostate cancer between 2004–2012 and treated with definitive-intent radiation therapy, as captured in the National Cancer Database. This database is a hospital-based registry that collects an estimated 70% of all diagnosed malignancies in the United States. Results There were 299,186 patients identified, of which 4,962 (1.7%) were identified as receiving SBRT as primary treatment. Of those men, 2,082 had low risk disease (42.0%), 2,201 had intermediate risk disease (44.4%), and 679 had high risk disease (13.7%). The relative utilization of SBRT increased from 0.1% in 2004 to 4.0% in 2012. Initially SBRT was more commonly used in academic programs, though as time progressed there was a shift to favor an increased absolute number of men treated in the community setting. Delivery of five separate treatments was the most commonly utilized fractionation pattern, with 4,635 patients (91.3%) receiving this number of treatments. The most common dosing pattern was 725 cGy × 5 fractions (49.6%) followed by 700 cGy × 5 fractions (21.3%). conclusions Extreme hypofractionation via SBRT is slowly increasing acceptance. Currently 700-725 cGy × 5 fractions appears to be the most commonly employed scheme. As further long-term data regarding the safety and efficacy emerges, the relative utilization of this modality is expected to continue to increase.
Drug-induced Hypersensitivity Syndrome(DIHS): A Reaction Induced by a Complex Interplay among Herpesviruses and Antiviral and Antidrug Immune Responses.

A relationship between viral infections and the simultaneous or subsequent development of allergic inflammation has often been observed in various clinical situations. Recent studies suggest an intimate relationship between reactivations of herpesviruses including human herpesvirus 6 (HHV-6) and the development of a severe systemic hypersensitivity reaction referred to as drug-induced hypersensitivity syndrome (DIHS). This syndrome has several important clinical features that cannot be solely explained by drug antigen-driven oligoclonal expansion of T cells: they include paradoxical worsening of clinical symptoms after discontinuation of the causative drug. In view of the similarity to GVHD or immune reconstitution syndrome (IRS) in clinical manifestations and emergence of viral infections, the clinical symptoms observed during the course of DIHS and GVHD are likely to be mediated by antiviral T cells that can cross-react with the drug and alloantigens, respectively. In considering common intrinsic properties of the causative drugs to potentially induce immunosuppression, re-constitution of a valid immune response to these viruses, which is typically observed in IRS, may be the most crucial process that takes place after withdrawal of the causative drug in patients with DIHS. Thus, this syndrome should be regarded as a reaction induced by a complex interplay among several herpesviruses (EB virus, HHV-6, HHV-7, and cytomegalovirus), antiviral immune responses, and drug-specific immune responses. This review includes discussion of the pathomechanism, the clinical symptoms, laboratory findings, pathological findings and therapy.