Miracle-dz/UniFAR-FTUs huggingface dataset:
Down‐regulation of p16 and MGMT promotes the anti‐proliferative and pro‐apoptotic effects of 5‐Aza‐dC and radiation on cervical cancer cells

Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O‐6‐methylguanine‐DNA methyltransferase (MGMT) was reversed, although their expression was suppressed. 5‐Aza‐dC inhibited E6 and E7 expression and up‐regulated p53, p21, and Rb expression. Cells transfected with siRNAs targeting p16 and MGMT as well as cells stimulated with 5‐Aza‐dC were arrested in S phase, and the expression of p53, p21, and Rb was up‐regulated more significantly. However, when cells were stimulated with 5‐Aza‐dC after transfection with siRNAs targeting p16 and MGMT, proliferation decreased significantly, and the percentage of cells in the sub‐G1 peak and in S phase was significantly increased, suggesting a marked increase in apoptosis. But E6 and E7 overexpression could rescue the observed effects in proliferation. Furthermore, X‐ray radiation caused cells to arrest in G2/M phase, but cells transfected with p16‐ and MGMT‐targeted siRNAs followed by X‐ray radiation exhibited a significant decrease in proliferation and were shifted toward the sub‐G1 peak, also indicating enhanced apoptosis. In addition, the effects of 5‐Aza‐dC and X‐ray radiation were most pronounced when MGMT expression was down‐regulated. Therefore, down‐regulation of p16 and MGMT expression enhances the anti‐proliferative effects of 5‐Aza‐dC and X‐ray radiation. This discovery may provide novel ideas for the treatment of cervical cancer.
The Oncogene Nup98-HOXA9 Induces Gene Transcription in Myeloid Cells*

The nucleoporin Nup98 gene is frequently rearranged in acute myelogenous leukemia (AML). In most cases this results in fusion of the N terminus of Nup98 to the DNA binding domain of a homeodomain transcription factor. The prototype of these fusions, Nup98-HOXA9, is associated with human AML and induces AML in mouse models. To understand the mechanisms by which Nup98-HOXA9 causes AML, we expressed it in myeloid cells and identified its target genes using high density oligonucleotide microarrays. The analysis was performed in triplicate and was confirmed by quantitative real time PCR. Of the 102 Nup98-HOXA9 target genes identified, 92 were up-regulated, and only 10 were down-regulated, suggesting a transcriptional activation function. A similar analysis of wild-type HOXA9 revealed 13 target genes, 12 of which were up-regulated, and 1 was down-regulated. In contrast, wild-type Nup98 had no effect on gene expression, demonstrating that the HOXA9 DNA binding domain is required for gene regulation. Co-transfection experiments using a luciferase reporter linked to the promoter of one of the Nup98-HOXA9 target genes confirmed up-regulation at the transcriptional level by Nup98-HOXA9 but not by either HOXA9 or Nup98. These data indicate that Nup98-HOXA9 is an aberrant transcription factor whose activity depends on the HOXA9 DNA binding domain but has a stronger and wider transcriptional effect than HOXA9. Several of the genes regulated by Nup98-HOXA9 are associated with increased cell proliferation and survival as well as drug metabolism, providing insights into the pathogenesis and epidemiology of Nup98-HOXA9-induced AML.
MMSE-Based Filter Designs for Cognitive Multiuser Two-Way Relay Networks

This paper considers cognitive multiuser two-way relay networks (MU-TRNs) where multiple secondary users (SUs) concurrently exchange their data with other SUs with an aid of a two-way relay in licensed primary networks. In this paper, we particularly focus on linear relay filter designs that effectively minimize the mean square error of SUs while providing a certain level of quality of service for the primary network. To this end, we first propose an iterative algorithm that identifies a solution based on an alternating optimization technique. Then, a closed-form relay filter design is presented, which employs a high signal-to-noise ratio approximation to reduce the computational complexity. Through the simulation results, we confirm that the proposed closed-form relay filter design outperforms conventional approaches and provides the performance close to the proposed iterative algorithm with much reduced complexity.
Active Learning and Visual Analytics for Stance Classification with ALVA

The automatic detection and classification of stance (e.g., certainty or agreement) in text data using natural language processing and machine-learning methods creates an opportunity to gain insight into the speakers’ attitudes toward their own and other people’s utterances. However, identifying stance in text presents many challenges related to training data collection and classifier training. To facilitate the entire process of training a stance classifier, we propose a visual analytics approach, called ALVA, for text data annotation and visualization. ALVA’s interplay with the stance classifier follows an active learning strategy to select suitable candidate utterances for manual annotaion. Our approach supports annotation process management and provides the annotators with a clean user interface for labeling utterances with multiple stance categories. ALVA also contains a visualization method to help analysts of the annotation and training process gain a better understanding of the categories used by the annotators. The visualization uses a novel visual representation, called CatCombos, which groups individual annotation items by the combination of stance categories. Additionally, our system makes a visualization of a vector space model available that is itself based on utterances. ALVA is already being used by our domain experts in linguistics and computational linguistics to improve the understanding of stance phenomena and to build a stance classifier for applications such as social media monitoring.
An efficient algorithm for computing Boolean function expressions of S-boxes

This paper attempts to address the problem of Boolean function expression calculation of S-boxes in block ciphers, which has been the algebraic basis of construction and evaluation of the secure S-boxes. By adopting the swap memory method (SMM), an efficient algorithm is developed to generate the Boolean function expressions directly from the truth tables. The algorithm exhibits a number of advantages such as conceptual simplicity, memory economy and applicability in handling multi-output problems. Furthermore, the algorithm can be executed in a parallel manner. A complete example is studied to illustrate the efficiency of the algorithm.
Incidence and prevalence of hospital-acquired infections in a cohort of patients admitted to medical departments.

INTRODUCTION Hospital-acquired infections (HAI) are a significant cause of morbidity and mortality. Only point prevalence analyses of HAI have been recorded in Denmark. The aim of this study was to investigate the incidence and prevalence of HAI in patients admitted to departments of internal medicine. MATERIAL AND METHODS The study involved seven departments and was designed as a cohort study based on reviews of medical records. Except for patients who had previously been admitted within the preceding 30 days, the study included all patients admitted for more than 48 hours during the 45-day study period. HAI was defined according to the criteria established by the Center for Disease Control and Prevention, USA. RESULTS The incidence of HAI was 1.7 (62/3,568) per 100 days at risk (95% confidence interval (CI) 1.4-2.2), while the total prevalence of HAI was 9.7% (345/3,568) (95% CI 8.7-10.6). Exposure to bladder catheter was associated with an increased risk of urinary tract infection, incidence rate ratio 4.9; (95% CI 1.8-11.5). For the initial 14 days of hospitalization, the incidence of HAI was independent, while the prevalence increased linearly with duration of admittance. CONCLUSION The incidence of HAI was relatively constant during the initial 14-day-period of hospitalization, suggesting that shortening the period will have no major impact on the incidence of HAI. The prevalence was 9.7%, which is in line with results from prior studies.
Optimizing triangulations by curvature equalization

An algorithm that attempts to improve a triangulation by shifting the vertices so that curvature within the triangles is nearly equal is presented. Unnecessary triangles are removed. The method is an effective way of guaranteeing that the triangle vertices are points of higher curvature, and that the triangle edges correspond to distinctive edges on the surfaces. Triangulations of surfaces with constant curvature-and hence no distinctive features-will gain nothing from this or any other optimization algorithm. As demonstrated by the results, the techinque of moving triangle vertices can improve some triangulation models. Greatest improvements occur with surfaces characterized by sharp edges, such as the pyramid and ridge models. Less improvement occurs on models that already approximate the surface topology and/or have less distinctive features. <<ETX>>
The Zebra fish cassiopeia Mutant Reveals that SIL Is Required for Mitotic Spindle Organization

ABSTRACT A critical step in cell division is formation of the mitotic spindle, which is a bipolar array of microtubules that mediates chromosome separation. Here, we report that the SCL-interrupting locus (SIL), a vertebrate-specific cytosolic protein, is necessary for proper mitotic spindle organization in zebrafish and human cells. A homozygous lethal zebrafish mutant, cassiopeia (csp), was identified by a genetic screen for mitotic mutant. csp mutant embryos have an increased mitotic index, have highly disorganized mitotic spindles, and often lack one or both centrosomes. These phenotypes are caused by a loss-of-function mutation in zebrafish sil. To determine if the requirement for SIL in mitotic spindle organization is conserved in mammals, we generated an antibody against human SIL, which revealed that SIL localizes to the poles of the mitotic spindle during metaphase. Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly.
The Impact of Economic Policies on Economic Growth in a Group of Arabic Countries: Empirical Verification using Non-Stationary Panel Model

The economic literature shows the existence of a real impact of the economic policies on economic growth. Since the 1980s, these policies in Arab countries have experienced significant reforms that sought to give them more flexibility and efficiency. This work proposes a study of the impact of monetary, fiscal and exchange rate policies on economic activity of a group of Arab countries in that to estimate a growth function on these countries using the nonstationary panel data model. From the results found, it was possible to identify the impact of the economic policies on economic activity.
Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives

Synthesis and antimicrobial evaluation of some 6-aryl-5-cyano-2-thiouracil derivatives A series of 6-aryl-5-cyano-2-thiouracil derivatives (1a-d) was synthesized by the reaction of ethyl cyanoacetate with thiourea and aldehydes. These products were used as intermediate compounds for the synthesis of a number of thiouracil derivatives (2a-d to 10a-d). All compounds were screened for antibacterial and antifungal activities. Some of the prepared compounds, 6-(4-fluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2a), 4-oxo-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (2d), 6-(4-fluorophenyl)-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-cabonitrile (7a) and 4-hydrazino-2-thioxo-6-(3,4,5-trimethoxyphenyl)-1,2-dihydropyrimidine-5-carbonitrile (7d) revealed promising antimicrobial activity. Sinteza i antimikrobno vrednovanje nekoliko 6-aril-5-cijano-2-tiouracil derivata Polazeći iz etil-cijanoacetata, tiouree i odgovarajućeg aldehida sintetizirana je serija 6-aril-5-cijano-2-tiouracil derivata (1a-d), koji su potom upotrijebljeni za dobivanje tiouracil derivata (2a-d do 10a-d). Svim spojevima ispitano je antibakterijsko i antimikotsko djelovanje. Neki od sintetiziranih spojeva, 6-(4-fluorofenil)-4-okso-2-tiokso-1,2,3,4-tetrahidropirimidin-5-karboksamid (2a), 4-okso-2-tiokso-6-(3,4,5-trimetoksifenil)-1,2,3,4-tetrahidropirimidin-5-karboksamid (2d), 6-(4-fluorofenil)-4-hidrazino-2-tiokso-1,2-dihidropirimidin-5-kabonitril (7a) i 4-hidrazino-2-tiokso-6-(3,4,5-trimetoksifenil)-1,2-dihidropirimidin-5-karbonitril (7d) imaju značajno antimikrobno djelovanje.
Improved Detection of Circulating Aspergillus Antigen by Use of a Modified Pretreatment Procedure

ABSTRACT Detection of circulating galactofuranose (galf) antigens, including galactomannan (GM), by the Platelia Aspergillus (PA) enzyme-linked immunosorbent assay (ELISA) is an important tool in the early diagnosis of invasive aspergillosis (IA). We used a modified pretreatment technique (MT) on consecutive negative PA ELISA plasma samples from IA patients in order to improve the detection of the fungal components present. Plasma samples (52) were collected from healthy donors, and 174 plasma samples with a galactomannan index (GMI) below 0.5 were collected from 25 unclassifiable and 23 IA patients. The PA ELISA reactivity of pretreated samples was determined before (conventional technique [CT]) and after (MT) filtration using a Microcon filter with a 50-kDa cutoff (Millipore). For the MT, the sensitivity of the PA ELISA increased from 42.9% (CT) to 78.6% (MT) using a cutoff for the GMI of 1.5 in the probable and proven group, whereas specificity slightly decreased from 98.7% to 96.1% in the control group. The 10-fold concentration step increased the GMI as high as 121-fold. The MT resulted not only in positive reactivity in samples that tested negative with the CT but also in the earlier detection of antigen by 2 to 17 days.
Synthesis of monodisperse silver nanoparticles for ink-jet printed flexible electronics

In this study, monodisperse silver nanoparticles were synthesized with a new reduction system consisting of adipoyl hydrazide and dextrose at ambient temperature. By this facile and rapid approach, high concentration monodisperse silver nanoparticles were obtained on a large scale at low protectant/AgNO3 mass ratio which was highly beneficial to low cost and high conductivity. Based on the synthesized monodisperse silver nanoparticles, conductive inks were prepared with water, ethanol and ethylene glycol as solvents, and were expected to be more environmentally friendly. A series of electrocircuits were fabricated by ink-jet printing silver nanoparticle ink on paper substrate with a commercial printer, and they had low resistivity in the range of 9.18 × 10 − 8–8.76 × 10 − 8 Ω m after thermal treatment at 160 °C for 30 min, which was about five times that of bulk silver (1.586 × 10 − 8 Ω m). Moreover, a radio frequency identification (RFID) antenna was fabricated by ink-jet printing, and 6 m wireless identification was realized after an Alien higgs-3 chip was mounted on the printed antenna by the flip-chip method. These flexible electrocircuits produced by ink-jet printing would have enormous potential for low cost electrodes and sensor devices.
Metal gate work function engineering on gate leakage of MOSFETs

We present a systematic study of tunneling leakage current in metal gate MOSFETs and how it is affected by the work function of the metal gate electrodes. Physical models used for simulations were corroborated by experimental results from SiO/sub 2/ and HfO/sub 2/ gate dielectrics with TaN electrodes. In bulk CMOS results show that, at the same capacitance equivalent oxide thickness (CET) at inversion, replacing a poly-Si gate by metal reduces the gate leakage appreciably by one to two orders of magnitude due to the elimination of polysilicon gate depletion. It is also found that the work function /spl Phi//sub B/ of a metal gate affects tunneling characteristics in MOSFETs. It is particularly significant when the transistor is biased at accumulation. Specifically, the increase of /spl Phi//sub B/ reduces the gate-to-channel tunneling in off-biased n-FET and the use of a metal gate with midgap /spl Phi//sub B/ results in a significant reduction of gate to source/drain extension (SDE) tunneling in both n- and p-FETs. Compared to bulk FET, double gate (DG) FET has much lower off-state leakage due to the smaller gate to SDE tunneling. This reduction in off-state leakage can be as much as three orders of magnitude when high-/spl kappa/ gate dielectric is used. Finally, the benefits of employing metal gate DG structure in future CMOS scaling are discussed.
Efficacy of mobile context-aware notification management systems: A systematic literature review and meta-analysis

Notifications can be relevant but they can also decrease productivity when delivered at the wrong point in time. Smartphones are increasingly capable of detecting relevant context information with the goal to decrease the number of these badly timed interruptions. Accordingly, research on context-aware notification management systems (CNMSs) on mobile devices has received increasing attention recently, prototypes have been built and empirically evaluated. However, there exists no systematic overview of mobile CNMSs evaluating their efficacy. The objectives of the current work are therefore to identify relevant empirical studies that have assessed the efficacy of mobile CNMSs and to discuss the findings with respect to future work. A systematic literature review and meta-analysis was conducted to address these objectives. Consistent with prior work, two efficacy metrics were applied: response rate and response delay. A keyword-based search strategy was used and resulted in 1'634 studies, out of which 8 were relevant for the topic. Findings indicate that mobile CNMSs increase the response rate, while there was only little evidence that they reduce response time, too. Implications for researchers and practitioners are discussed and future research is outlined that aims at further increasing the efficacy of mobile CNMSs.
Protein Kinase D Mediates Mitochondrion-to-Nucleus Signaling and Detoxification from Mitochondrial Reactive Oxygen Species

ABSTRACT Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mechanisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-κB transcription factor, leading to induction of SOD2. Conversely, the FOXO3a transcription factor is dispensable for mROS-induced SOD2 induction. PKD-mediated MnSOD expression promotes increased survival of cells upon release of mROS, suggesting that mitochondrion-to-nucleus signaling is necessary for efficient detoxification mechanisms and cellular viability.
Identification of new members of Fertilisation Independent Seed Polycomb Group pathway involved in the control of seed development in Arabidopsis thaliana

In higher plants, double fertilisation initiates seed development. One sperm cell fuses with the egg cell and gives rise to the embryo, the second sperm cell fuses with the central cell and gives rise to the endosperm. The endosperm develops as a syncytium with the gradual organisation of domains along an anteroposterior axis defined by the position of the embryo at the anterior pole and by the attachment to the placenta at the posterior pole. We report that ontogenesis of the posterior pole in Arabidopsis thaliana involves oriented migration of nuclei in the syncytium. We show that this migration is impaired in mutants of the three founding members of the FERTILIZATION INDEPENDENT SEED (FIS) class, MEDEA (MEA), FIS2 and FERTILIZATION INDEPENDENT ENDOSPERM (FIE). A screen based on a green fluorescent protein (GFP) reporter line allowed us to identify two new loci in the FIS pathway, medicis and borgia. We have cloned the MEDICIS gene and show that it encodes the Arabidopsis homologue of the yeast WD40 domain protein MULTICOPY SUPRESSOR OF IRA (MSI1). The mutations at the new fis loci cause the same cellular defects in endosperm development as other fis mutations, including parthenogenetic development, absence of cellularisation, ectopic development of posterior structures and overexpression of the GFP marker.
Identifying securities to buy: The heuristic ri

In this study, we analyze the power of the individual return-to-volatility security performance heuristic (ri/stdi) to simplify the identification of securities to buy and, consequently, to form the optimal no short sales mean–variance portfolios. The heuristic ri/stdi is powerful enough to identify the long and shorts sets. This is due to the positive definiteness of the variance–covariance matrix – the key is to use the heuristic sequentially. At the investor level, the heuristic helps investors to decide what securities to consider first. At the portfolio level, the heuristic may help us find out whether it is a good idea to invest in equity to begin with. Our research may also help to integrate individual security analysis into portfolio optimization through improved security rankings.
Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2

Complete nucleotide sequencing of the RNAs of two unrelated neurovirulent isolates of Sabin-related poliovirus type 2 revealed that two nucleotides and one amino acid (amino acid 143 in the major capsid protein VP1) consistently departed from the sequences of the nonneurovirulent poliovirus type 2 712 and Sabin vaccine strains. This pattern of mutation appeared to be a feature common to all neurovirulent variants of poliovirus type 2.
Identification of higenamine in Radix Aconiti Lateralis Preparata as a beta2-adrenergic receptor agonist

AbstractAim:To screen beta2-adrenergic receptor (β2-AR) agonists from Radix Aconiti Lateralis Preparata (RALP) as potential drug leads for asthma using a sensitive cell-based agonist assay.Methods:The β2-AR gene was stably expressed by Chinese hamster ovary (CHO) cells also stably expressing a cyclic adenosine monophosphate (AMP) response element-linked enhanced green fluorescent protein reporter gene. The cells were used to screen agonists from high-performance liquid chromatographic fractions of an extract of RALP. The fraction with the highest activity was selected for further compound isolation and the study of the structure-activity relationship. Its active compound was further identified by chromatography and mass spectrometry.Results:Bioactivity-directed fraction-ation of the crude extract of RALP led to the isolation and characterization of the effective compound, namely hignamine. It could dose-dependently relax the isolated guinea pig trachea strip precontraction with acetylcholine with EC50 value of (2.60±0.36) × 10−5 mol/L. Further in vivo studies also displayed that hignamine could protect experimental asthma model induced by histamine in guinea pigs to prolong the latent periods of asthma.Conclusion:Hignamine, as a β2-AR agonist existing in the extract of RALP, is the key compound contributing to the successful relief of the bronchoconstriction.