Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular cloning, expression, and characterization of E2F transcription factor 4 from Antheraea pernyi

Abstract The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L. Quantitative real-time polymerase chain reaction analysis revealed that E2F4 expression was highest in the integument, followed by the fat body, silk glands, and haemocytes. The expression of E2F4 was upregulated in larvae challenged by bacterial (Escherichia coli, Micrococcus luteus), viral (nuclear polyhedrosis virus), and fungal (Beauveria bassiana) pathogens. These observations indicated that E2F4 is an inducible protein in the immune response of A. pernyi and probably in other insects.
Convex and non-convex approaches for cost efficiency models with fuzzy data

Classical cost efficiency (CE) measurement models require exact and accurate knowledge of the input and output values for each decision making unit (DMU). However, the observed values of the input and output data in real-world problems are often imprecise or vague. In recent years, fuzzy data envelopment analysis (DEA) has been successfully used to deal with imprecise or vague data in efficiency measurement. In this paper, we incorporate fuzzy set theory into the traditional CE measurement. We propose two approaches based on the convex DEA and non-convex free disposable hull (FDH) approach with fuzzy variables. The purpose of this paper is two-fold: 1) we develop a CE analysis for non-parametric convex methods based on fuzzy set theory; 2) we further develop a non-convex CE analysis model where the non-convexity is formulated based on the FDH approach. We also present a numerical example to demonstrate the applicability of the proposed models and exhibit the efficacy of the procedures and algorithms.
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial–mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.
The Metabolic Phenotype of Prostate Cancer

Prostate cancer is the most common non-cutaneous cancer in men in the United States. Cancer metabolism has emerged as a contemporary topic of great interest for improved mechanistic understanding of tumorigenesis. Prostate cancer is a disease model of great interest from a metabolic perspective. Prostatic tissue exhibits unique metabolic activity under baseline conditions. Benign prostate cells accumulate zinc, and this excess zinc inhibits citrate oxidation and metabolism within the citric acid cycle, effectively resulting in citrate production. Malignant cells, however, actively oxidize citrate and resume more typical citric acid cycle function. Of further interest, prostate cancer does not exhibit the Warburg effect, an increase in glucose uptake, seen in many other cancers. These cellular metabolic differences and others are of clinical interest as they present a variety of potential therapeutic targets. Furthermore, understanding of the metabolic profile differences between benign prostate versus low- and high-grade prostate cancers also represents an avenue to better understand cancer progression and potentially develop new diagnostic testing. In this paper, we review the current state of knowledge on the metabolic phenotypes of prostate cancer.
Are the Dysnatremias a Permanent Threat to the Critically Ill Patients?

Backgroud The dysnatremias (hyponatremia and hypernatremia) are relatively common findings on admission of intensive care unit (ICU) patients and may represent a major risk. The aim of the study was to assess the ability of serum sodium levels and the Acute Physiology and Chronic Health Evaluation II (APACHE II) to predict mortality of surgical critically ill patients. Methods One hundred and ninety-five surgical patients (62% males and 38% females; mean age of 51.8 ± 17.3 years) admitted to the ICU in the postoperative phase were retrospectively studied. The patients were divided into survivors (n = 152) and non-survivors (n = 43). APACHE II, and serum sodium levels at admission, 48 h and discharge were analyzed by generation of receiver operating characteristic (ROC) curves. Results The mean APACHE II was 16.3 ± 8.3 (13.6 ± 6.1 for survivors and 25.5 ± 8.5 for non-survivors). The area under the ROC curve for APACHE II was 0.841 (0.782 - 0.889) and 0.721 (0.653 - 0.783), 0.754 (0.653 - 0.783) and 0.720 (0.687 - 0.812) for serum sodium level at admission, 48 h and discharge, respectively. Conclusion Even though APACHE II scoring system was the most effective index to predict mortality in the surgical critically ill patients, the serum sodium levels on admission may also be used as an independent predictor of outcome.
Angiogenic switch occurs late in squamous cell carcinomas of human skin

Angiogenesis is a crucial event in carcinogenesis and its onset has been associated with premalignant tumour stages. In order to elucidate the significance of angiogenesis in different stages of epithelial skin tumours, we analysed the vessel density in ten normal skin samples, 14 actinic keratosis (AK), 12 hypertrophic AKs, and in nine early- and 16 late-stage squamous cell carcinomas (SCCs). Mean vascular density was quantitated by counting the number of CD 31-immunostained blood vessels and by morphometric assessment of stained vessel area by computer-assisted image analysis. The results from both methods were well correlated. Mean vascular density was similar in normal dermis and in AK, and only slightly elevated in hypertrophic AKs and early SCC stages (tumour thickness < 2 mm). Only late-stage SCCs infiltrating the subcutis exhibited a significant increase in vascularization. Vessel density was independent of tumour localization, degree of proliferation and inflammatory cell infiltration. Furthermore, tumour vascularization was not correlated with the expression of vascular endothelial growth factor, a major angiogenic factor, as revealed by in situ hybridization and immunohistochemistry. The restriction of enhanced vascularization to increased tumour thickness may be a major reason for the rather low metastatic spread of cutaneous SCCs. © 2000 Cancer Research Campaign
Bioinformatics Applications Note Phylogenetics Hybridnet: a Tool for Constructing Hybridization Networks

Motivations: When reticulation events occur, the evolutionary history of a set of existing species can be represented by a hybridization network instead of an evolutionary tree. When studying the evolutionary history of a set of existing species, one can obtain a phylogenetic tree of the set of species with high confidence by looking at a segment of sequences or a set of genes. When looking at another segment of sequences, a different phylogenetic tree can be obtained with high confidence too. This indicates that reticulation events may occur. Thus, we have the following problem: given two rooted phylogenetic trees on a set of species that correctly represent the tree-like evolution of different parts of their genomes, what is the hybridization network with the smallest number of reticulation events to explain the evolution of the set of species under consideration? Results: We develop a program, named HybridNet, for constructing a hybridization network with the minimum number of reticulate vertices from two input trees. We first implement the O(3 d n)-time algorithm by Whidden et al. for computing a maximum (acyclic) agreement forest. Our program can output all the maximum (acyclic) agreement forests. We then augment the program so that it can construct an optimal hybridization network for each given maximum acyclic agreement forest. To our knowledge, this is the first time that optimal hybridization networks can be rapidly constructed.
Clonal Variability of PC12 Pheochromocytoma Cells with Respect to Catecholamine Biosynthesis

Abstract: Clonal variants of PC12 cells with respect to catecholamine biosynthesis were isolated, and the catecholamine content was measured by high performance liquid chromatography with electrochemical detection. The dopamine content of 13 subclones, which were selected and isolated in tyrosine‐free medium, was substantially higher than the control level: 0.91 ± 0.10 nmol/mg protein (mean ± SEM; n = 3). In contrast, the noradrenaline content showed a marked heterogeneity: only two subclones contained noradrenaline levels similar to or higher than the control level: 0.40 ± 0.05 (n = 5). The rest of them contained below the level of 0.20, and only negligible amounts of noradrenaline were found in four subclones. Thus, the noradrenaline‐to‐dopamine ratio varied widely between 0.003:1 and 0.53:1. This divergence of the noradrenaline content appears to be related to differing levels of dopamine β‐monooxygenase activity. The administration of ascorbate to the medium alone, however, did not restore the level of noradrenaline to the normal level in a subclone. Heterogeneity of the response to applied glucocorticoid was also demonstrated.
Analysis of the Free-Energy Surface of Proteins from Reversible Folding Simulations

Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical λ-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.
The C-Terminal Domain of DnaQ Contains the Polymerase Binding Site

ABSTRACT The Escherichia coli dnaQ gene encodes the 3′→5′ exonucleolytic proofreading (ɛ) subunit of DNA polymerase III (Pol III). Genetic analysis of dnaQ mutants has suggested that ɛ might consist of two domains, an N-terminal domain containing the exonuclease and a C-terminal domain essential for binding the polymerase (α) subunit. We have created truncated forms ofdnaQ resulting in ɛ subunits that contain either the N-terminal or the C-terminal domain. Using the yeast two-hybrid system, we analyzed the interactions of the single-domain ɛ subunits with the α and θ subunits of the Pol III core. The DnaQ991 protein, consisting of the N-terminal 186 amino acids, was defective in binding to the α subunit while retaining normal binding to the θ subunit. In contrast, the NΔ186 protein, consisting of the C-terminal 57 amino acids, exhibited normal binding to the α subunit but was defective in binding to the θ subunit. A strain carrying the dnaQ991allele exhibited a strong, recessive mutator phenotype, as expected from a defective α binding mutant. The data are consistent with the existence of two functional domains in ɛ, with the C-terminal domain responsible for polymerase binding.
A power-saving standby method to extend battery life in dual-mode cellular phones

Dual-mode cellular phones, including smartphones, are recently attracting much attention from both users and telecom operators throughout many countries. To avoid traffic concentration generated by these devices on 3G networks, it is important to lead users to connect with fixed networks via WLAN. However, keeping both 3G and WLAN interfaces on consumes a great deal of power, which considerably shortens the standby time. To achieve longer battery life, we propose a power-saving standby method (PSSM) whose features are: (1) constant deactivation of the WLAN interface except for when required; (2) no additional functions in a mobile operator's network; and (3) avoidance of a WLAN AP search distant from a cellular phone. We implemented PSSM as a BREW application and measured the electrical current in a cellular phone as well as the delay in email retrieval transaction. Experimental results using the prototype system show that PSSM achieves about 73%-134% longer battery life than a conventional dual-mode cellular phone, while PSSM keeps the application transaction delay short by reducing unproductive WLAN AP searches.
Aberrant Vimentin Methylation Is Characteristic of Breast Cancer

Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor genes, and other genes. Increased vimentin gene expression has been reported in various tumor cell lines and tissues including breast cancer. In addition, methylation of the vimentin gene was described as a marker in several malignant tumors. Objective: The aim of this study is to determine the existence of a potential relationship between the methylation state of the vimentin gene and its prognostic value in breast cancer patients and its correlation with vimentin protein expression in the serum. Patients and Methods: The methylation status of the vimentin gene was examined in primary infiltrating ductaltumors and the surrounding normal tissues derived from 50 breast cancer patients enrolled for either modified radical mastectomy or conservative breast surgery using quantitative methylation-specific polymerase chain reaction (qMSP), serum vimentin levels were determined using ELISA, and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Out of 50 breast cancer patients, 18 (36%) exhibited positive methylation of vimentin gene while 32 (64%) exhibited negative vimentin genemethylation in their tumors. Subsequently clinicopathological data were correlated with the vimentin genemethylation score. A significant association was found between negative vimentin methylation, and both serum vimentin protein level (p 0.001) and the triple negative breast cancer subtype (TNBCs) (p = 0.004). Using receiver-operating characteristic (ROC) curve analysis, a cut off value of and the ROC curve showed an area under the curve (AUC) of 0.684 (p = 0.029). Conclusion: Our study showed that the vimentin gene is frequently hypomethylated in breast cancer tissues, and that negative methylation status is always associated with high serum vimentin protein expression levels. Also we reported a significant association between negative vimentin methylation and TNBC subtype which is known to have an aggressive clinical course. Taken together, these results might have important implications for the design of novel therapeutic interventions for breast cancer patients. However, further studies with larger sample size are needed to validate these observations.
Combined EEG-fMRI and tractography to visualise propagation of epileptic activity

In a patient with refractory temporal lobe epilepsy, EEG-fMRI showed activation in association with left anterior temporal interictal discharges, in the left temporal, parietal and occipital lobes. Dynamic causal modelling suggested propagation of neural activity from the temporal focus to the area of occipital activation. Tractography showed connections from the site of temporal lobe activation to the site of occipital activation. This demonstrates the principle of combining EEG-fMRI and tractography to delineate the pathways of propagation of epileptic activity.
Constellation design for transmission over nonlinear satellite channels

In this paper we use a variation of simulated annealing algorithm for optimizing two-dimensional constellations with 32 signals. The main objective is to maximize the symmetric pragmatic capacity under the peak-power constraint. The method allows the joint optimization of constellation and binary labeling. We also investigate the performance of the optimized constellation over nonlinear satellite channel under additive white Gaussian noise. We consider the performance over systems with and without pre-distorters. In both cases the optimized constellations perform considerably better than the conventional Amplitude Phase Shift Keying (APSK) modulations, used in the current digital video broadcasting standard (DVB-S2) on satellite channels. Based on our optimized constellations, we also propose a new labeling for the 4+12+16-APSK constellation of the DVB-S2 standard which is Gray over all rings.
Visual Web Information Extraction with Lixto

We present new techniques for supervised wrapper generation and automated web information extraction, and a system called Lixto implementing these techniques. Our system can generate wrappers which translate relevant pieces of HTML pages into XML. Lixto, of which a working prototype has been implemented, assists the user to semi-automatically create wrapper programs by providing a fully visual and interactive user interface. In this convenient user-interface very expressive extraction programs can be created. Internally, this functionality is reected by the new logicbased declarative language Elog. Users never have to deal with Elog and even familiarity with HTML is not required. Lixto can be used to create an \XML-Companion" for an HTML web page with changing content, containing the continually updated XML translation of the relevant information.
Antenna Violation Avoidance/Fixing for X-clock routing

As the IC fabrication technology gets into the nanometer era, antenna effect plays an important role in determining the yield and reliability of VLSI circuits. This work proposes a discharge-path-based antenna effect detection method. Based on the proposed detection method, two novel jumper insertion and layer assignment algorithms are presented for fixing antenna violations. Additionally, via delay is considered in delay calculation, and wire sizing technique is applied for clock skew compensation. Given an X-architecture clock tree with n clock sinks, layer configuration, and the upper bound for antenna effect, the proposed PADJILA algorithm runs in O(n2) to achieve antenna violation free. Experimental results on benchmarks show that our work significantly outperforms than the existing works.
Defect Analysis and Reliability Assessment for Transactional Web Applications

In this research, we analyze defects collected from different failure sources and use it for reliability assessment. Failure is the inability of a system or component to perform its required functions within specified performance requirements. Reliability is the probability of failure-free operations, and it is one of the most important quality attribute for the users of web applications. Reliability analysis and modeling can help Web service providers to assess current reliability, predict future reliability, and quantify potential improvement to reach reliability target. The failure information and the related workload measurements are required input for various reliability models under variable work load such as modeling transactional web applications. In this paper, we used session tracking data in addition to web server logs to characterize and measure the variable application workload. Session data provides accurate measurements of web applications' usage time such as the number of transactions that are required for reliability analysis. In addition to web failures recorded in web logs and defect tracking system, we also considered failures from the server side application error logs to quantify unique failures that occur on the web server. We applied different reliability assessment approaches covering time domain and input domain on data from our case study application and demonstrated the applicability and effectiveness of our approach.
Time-dependent solutions for particle-size segregation in shallow granular avalanches

Rapid shallow granular free-surface flows develop in a wide range of industrial and geophysical flows, ranging from rotating kilns and blenders to rock-falls, snow slab-avalanches and debris-flows. Within these flows, grains of different sizes often separate out into inversely graded layers, with the large particles on top of the fines, by a process called kinetic sieving. In this paper, a recent theory is used to construct exact time-dependent two-dimensional solutions for the development of the particle-size distribution in inclined chute flows. The first problem assumes the flow is initially homogeneously mixed and is fed at the inflow with homogeneous material of the same concentration. Concentration shocks develop during the flow and the particles eventually separate out into inversely graded layers sufficiently far downstream. Sections with a monotonically decreasing shock height, between these layers, steepen and break in finite time. The second problem assumes that the material is normally graded, with the small particles on top of the coarse ones. In this case, shock waves, concentration expansions, non-centred expanding shock regions and breaking shocks develop. As the parameters are varied, nonlinearity leads to fundamental topological changes in the solution, and, in simple-shear, a logarithmic singularity prevents a steady-state solution from being attained.