Miracle-dz/UniFAR-FTUs huggingface dataset:
Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents.

BACKGROUND The cyclooxygenase-2 (COX-2) inhibitor celecoxib is thought to act as a chemopreventive agent by sensitizing cancer cells to apoptotic signals. Other COX-2 inhibitors, such as rofecoxib, are two orders of magnitude less potent than celecoxib at inducing apoptosis. The molecular structures of celecoxib and rofecoxib were used as starting points to examine the structural features that contribute to this discrepancy. METHODS We used a systematic chemical approach to modify the structures of celecoxib and rofecoxib to produce a series of compounds that were tested for their effects on the viability of human prostate cancer PC-3 cells and their ability to induce apoptosis in these cells. Cell viability was measured by the trypan blue dye exclusion assay, and apoptosis was measured by an enzyme-linked immunosorbent assay that quantifies DNA cleavage and by western blot detection of poly(ADP-ribose) polymerase (PARP) cleavage. Western blotting was used to monitor the effects of the compounds on phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated kinase 2 (ERK2), two components of celecoxib-induced apoptosis signaling. Monte Carlo simulations were used to molecularly model the surface electrostatic potential and electron density of selected compounds. All statistical tests were two-sided. RESULTS The structural requirements for the induction of apoptosis in PC-3 cells were different from those for COX-2 inhibition. Structure-function analysis indicated that the induction of apoptosis by compounds derived from COX-2 inhibitors required a bulky terminal phenyl ring, a heterocyclic system with negative electrostatic potential, and a benzenesulfonamide or benzenecarboxamide moiety. These derivatives mediated apoptosis by facilitating the dephosphorylation of Akt and ERK2, irrespective of their COX-2 inhibitory activities. CONCLUSION A new class of compounds that induce apoptosis by targeting Akt and ERK2 signaling pathways in human prostate cancer cells can be synthesized by modifying existing COX-2 inhibitors.
Interactions between Organic and Inorganic Phases in PA- and PU/PA-Modified-Cement-Based Materials

In this paper, two types of acrylics, polyacrylate (PA), a copolymer of methyl methacrylate, acrylic acid, and others, and polyurethane-modified PA (PU/PA), are investigated in their interactions with inorganic phases in polymer-modified cement-based mixtures and in their mechanisms in improving both mechanical properties and durability of cement-based materials. In these investigations, the total organic carbon content (TOC) method is used to study the adsorption of polymer particles in mixtures. An aqueous tube test, x-ray diffraction (XRD), thermal gravity analysis (TGA), and Fourier transform infrared spectroscopy (FTIR) are employed to study the possible chemical reactions between the latexes and cement hydrates. Scanning electron microscopy (SEM) and energy-dispersive x-ray analysis (EDX) are used to observe the film formation and the final morphology of PA- and PU/PA-modified mortars. PU/PA latex is found to be relatively stable, and the behaviors of PU/PA-modified mixtures can be explained by Oham.
Control of the head in response to tilt of the body in normal and labyrinthine‐defective human subjects.

1. Head movement responses to discrete, unpredictable tilts of the trunk from earth upright were studied in normal and labyrinthine‐defective (LD) subjects. Tilts of the seated, restrained trunk, were delivered in pitch and roll about head‐centred axes and approximated raised cosine displacements with peak amplitudes of 20‐30 deg and durations of 1.5‐2 s. Subjects performed mental arithmetic with eyes closed or read earth‐fixed text. 2. At the onset of tilt the head momentarily lagged behind the trunk because of inertia. Subsequently, head control varied widely with three broad types: (i) head relatively fixed to the trunk (in normal subjects and some patients); (ii) head unstable, falling in the direction of gimbal tilt (typical of acute patients for pitch motion); (iii) compensatory head movement in the opposite direction to gimbal tilt (observed consistently in normal subjects and in well‐adapted patients). 3. EMG was well developed in subjects with compensatory head movement and consisted of an initial burst of activity at minimum latencies of 25‐50 ms (means 72‐108 ms), followed by a prolonged peak; both occurring in the ‘side up’ neck muscles, appropriate for righting the head. These muscles are shortened during the initial head lag so the responses cannot be stretch reflexes. In normal subjects their origin is predominantly labyrinthine but in patients they may be an ‘unloading response’ of the neck. 4. Head stability in space was superior with the visual task for all subjects but vision only partially compensated for labyrinthine signals in unstable patients. 5. Modelling the responses to tilt suggests that, in LD subjects, the short‐latency burst could be driven by signals from the neck of the relative acceleration between head and trunk tilt. The longer latency EMG could be driven by a signal of head tilt in space. Normally, this signal is probably otolithic. In patients it could be synthesized from summing proprioceptive signals of position of head on trunk with trunk tilt.
Lung Function Measurements in Rodents in Safety Pharmacology Studies

The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies.
Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial

OBJECTIVE To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. RESEARCH DESIGN AND METHODS Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11–13 yr). Participants were 347,978 men aged 35–57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. RESULTS Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level—overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels. CONCLUSIONS These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.
A New Algorithm for Hiding Gray Images using Blocks

As vast channels for communication such as the Internet are becoming popular, the security of digital media becomes a greater concern. Steganography is one of the techniques used to make detecting the transmitted data over channels more difficult, as hiding a message reduces the probability of detecting this message. In this paper we suggest a new steganography algorithm for hiding a gray image in one another. The cover is divided into blocks of equal sizes. Each block size equals the size of the embedding image. The results drawn in this paper with the similarity = 0.9717 are more improved and give the clear picture of the object
Trp-145 Is Essential for the Binding of 25-Hydroxyvitamin D3 to Human Serum Vitamin D-binding Protein (*)

Chemical modification of specific amino acid residues in a protein has been a valuable tool in identifying amino acid residues that are responsible for ligand binding of a protein. In the present investigation, we targeted Trp and His residues in human serum vitamin D-binding protein (hDBP) by modifying them with specific chemical modifiers. We also evaluated the results of these modifications in the binding of 25-hydroxy[26(27)-3H]vitamin D3 ([3H]25-OH-D3) to hDBP. We observed a dose-dependent loss of binding activity by N-bromosuccinimide (specific for Trp). Similar results were observed with diethylpyrocarbonate (specific for His). Furthermore, loss of [3H]25-OH-D3-binding was protected by preincubation of hDBP samples with an excess of 25-hydroxyvitamin D3. These results strongly emphasized the importance of Trp (single residue at position 145) and 1 His residue (out of a total of 6) in the vitamin D sterol-binding by vitamin D-binding protein.
Learning Domain-Specific Word Embeddings from Sparse Cybersecurity Texts

Word embedding is a Natural Language Processing (NLP) technique that automatically maps words from a vocabulary to vectors of real numbers in an embedding space. It has been widely used in recent years to boost the performance of a vari-ety of NLP tasks such as Named Entity Recognition, Syntac-tic Parsing and Sentiment Analysis. Classic word embedding methods such as Word2Vec and GloVe work well when they are given a large text corpus. When the input texts are sparse as in many specialized domains (e.g., cybersecurity), these methods often fail to produce high-quality vectors. In this pa-per, we describe a novel method to train domain-specificword embeddings from sparse texts. In addition to domain texts, our method also leverages diverse types of domain knowledge such as domain vocabulary and semantic relations. Specifi-cally, we first propose a general framework to encode diverse types of domain knowledge as text annotations. Then we de-velop a novel Word Annotation Embedding (WAE) algorithm to incorporate diverse types of text annotations in word em-bedding. We have evaluated our method on two cybersecurity text corpora: a malware description corpus and a Common Vulnerability and Exposure (CVE) corpus. Our evaluation re-sults have demonstrated the effectiveness of our method in learning domain-specific word embeddings.
Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection.

BACKGROUND Recurrence is a major factor leading to treatment failure and death in gastric cancer (GC) patients following surgical resection. Importantly, the prediction of recurrence is critical in improving clinical outcomes. We isolated a group of microRNAs (miRNAs) and evaluated their usefulness as prognostic markers for the recurrence of GC. PATIENTS AND METHODS A total of 65 GC patients were selected for systematic analysis, 29 patients with recurrence and 36 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize classifiers from primary tumor samples (n = 8). Following, we validated these predictors both in frozen fresh and paraffin-embedded tissue samples (n = 57) using quantitative PCR. RESULTS We have identified 17 differential miRNAs including 10 up-regulated and 7 down-regulated miRNAs in recurrence group. Using k-top scoring pairs (k-TSP) method, we further ascertained hsa-miR-375 and hsa-miR-142-5p as a classifier to recognize recurrence and nonrecurrence cases both in the training and test samples. Moreover, we validated this classifier in 34 frozen fresh tissues and 38 paraffin-embedded tissues with consistent sensitivity and specificity with training set; among them, 15 cases were matched. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-375 and low level of hsa-miR-142-5p (P < 0.001). In addition, we evaluated that hsa-miR-375 and hsa-miR-142-5p were involved in regulating target genes in several oncogenic signal pathways, such as TP53, MAPK, Wnt and vascular endothelial growth factor. CONCLUSION Our results indicate that the combination of hsa-miR-375 and hsa-miR-142-5p as a predictor of disease progression has the potential to predict recurrence risk for GC patients.
Capturing evolving visit behavior in clickstream data

Many online sites, both retailers and content providers, routinely monitor visitor traffic as a useful measure of their overall success. However, simple summaries such as the total number of visits per month provide little insight about individual-level site-visit patterns, especially in a changing environment such as the Internet. This article develops an individual-level model for evolving visiting behavior based on Internet clickstream data. We capture cross-sectional variation in site-visit behavior as well as changes over time as visitors gain experience with the site. In addition, we examine the relationship between visiting frequency and purchasing propensity at an e-commerce site. We find evidence supporting the notion that people who visit a retail site more frequently have a greater propensity to buy. We also show that changes (i.e., evolution) in an individual's visit frequency over time provides further information regarding which customer segments are likely to have higher purchasing conversion rates.
DOMAIN KEYWORD EXTRACTION TECHNIQUE : A NEW WEIGHTING METHOD BASED ON FREQUENCY ANALYSIS

On-line text documents rapidly increase in size with the growth of World Wide Web. To manage such a huge amount of texts,several text miningapplications came into existence. Those applications such as search engine, text categorization, summarization, and topic detection are based on feature extraction.It is extremely time consuming and difficult task to extract keyword or feature manually.So an automated process that extracts keywords or features needs to be established.This paper proposes a new domain keyword extraction technique that includes a
Three-Dimensional Image Reconstruction of Targets Under the Illumination of Terahertz Gaussian Beam—Theory and Experiment

In this paper, the wave equation based on phase shift migration technique is extended for terahertz 3-D imaging with quasi-optical transceivers. An analytical expression of the reconstructed 3-D point-spread function for targets under the illumination of a terahertz Gaussian beam was derived with this reconstruction technique. The quantitative relationship between the imaging quality and the parameters of the transmitted Gaussian beam was obtained, which provides a good criterion to be followed when designing the terahertz quasi-optical transceivers in the imaging systems. Moreover, the spatial sampling criterion was derived strictly which is also quantitatively related to the parameters of the transmitted Gaussian beam. Simulation results with fairly good agreement were given to verify the theoretical results derived in this paper. Finally, a monostatic prototype imager with a Gaussian beam transceiver was designed for the proof-of-principle experiments in 0.2-THz band. The 3-D imaging results of different targets and a mannequin with concealed threat objects were given to demonstrate the theoretical results obtained in this paper and the effectiveness of the 3-D terahertz image reconstruction for security applications.
DBI inflation in N = 1 supergravity

It was recently demonstrated that, when coupled to N=1 supergravity, the Dirac-Born-Infeld (DBI) action constructed from a single chiral superfield has the property that when the higher-derivative terms become important, the potential becomes negative. Thus, DBI inflation cannot occur in its most interesting, relativistic regime. In this paper, it is shown how to overcome this problem by coupling the model to one or more additional chiral supermultiplets. In this way, one obtains effective single real scalar field DBI models with arbitrary positive potentials, as well as multiple real scalar field DBI inflation models with hybrid potentials.
Patterns of widespread decline in North American bumble bees

Bumble bees (Bombus) are vitally important pollinators of wild plants and agricultural crops worldwide. Fragmentary observations, however, have suggested population declines in several North American species. Despite rising concern over these observations in the United States, highlighted in a recent National Academy of Sciences report, a national assessment of the geographic scope and possible causal factors of bumble bee decline is lacking. Here, we report results of a 3-y interdisciplinary study of changing distributions, population genetic structure, and levels of pathogen infection in bumble bee populations across the United States. We compare current and historical distributions of eight species, compiling a database of >73,000 museum records for comparison with data from intensive nationwide surveys of >16,000 specimens. We show that the relative abundances of four species have declined by up to 96% and that their surveyed geographic ranges have contracted by 23–87%, some within the last 20 y. We also show that declining populations have significantly higher infection levels of the microsporidian pathogen Nosema bombi and lower genetic diversity compared with co-occurring populations of the stable (nondeclining) species. Higher pathogen prevalence and reduced genetic diversity are, thus, realistic predictors of these alarming patterns of decline in North America, although cause and effect remain uncertain.
Network-Based Analysis Reveals Functional Connectivity Related to Internet Addiction Tendency

Preoccupation and compulsive use of the internet can have negative psychological effects, such that it is increasingly being recognized as a mental disorder. The present study employed network-based statistics to explore how whole-brain functional connections at rest is related to the extent of individual’s level of internet addiction, indexed by a self-rated questionnaire. We identified two topologically significant networks, one with connections that are positively correlated with internet addiction tendency, and one with connections negatively correlated with internet addiction tendency. The two networks are interconnected mostly at frontal regions, which might reflect alterations in the frontal region for different aspects of cognitive control (i.e., for control of internet usage and gaming skills). Next, we categorized the brain into several large regional subgroupings, and found that the majority of proportions of connections in the two networks correspond to the cerebellar model of addiction which encompasses the four-circuit model. Lastly, we observed that the brain regions with the most inter-regional connections associated with internet addiction tendency replicate those often seen in addiction literature, and is corroborated by our meta-analysis of internet addiction studies. This research provides a better understanding of large-scale networks involved in internet addiction tendency and shows that pre-clinical levels of internet addiction are associated with similar regions and connections as clinical cases of addiction.
Automated Architectural Exploration for Signal Processing Algorithms

This paper presents a design environment for efficiently generating application-specific intellectual property (IP) cores for system level signal processing algorithms. We present our view of a framework that combines common electronic design automation (EDA) tools to alleviate the designer from manually constructing the hardware models and analyzing their performance. We use our framework to efficiently implement design optimizations that improve the performance of the overall hardware architectures. Our framework is well suited for designers with a range of signal processing and hardware expertise. Our framework generates the dedicated IP cores and estimates the performance such as area, critical path delay, and latency within seconds. Parts of our framework also compare different hardware designs for various digital signal processing (DSP) algorithms and allows the designer to make architectural decisions earlier in the hardware design process. We use a GUI-based framework invoked from MATLAB to automatically build and analyze the hardware designs. Our framework generates efficient hardware designs described in SystemC and Verilog code, along with the performance metrics for each architecture. We illustrate the use of our framework by exploring and analyzing architectural variations of two case studies: finite impulse response (FIR) filters and adaptive channel equalizers
Deformation Strengthening of Biopolymer in Nacre

Nacre is an ultratough natural nanocomposite found in mollusc shells. It consists of hard aragonite nanocrystals and a soft biopolymer matrix. Apart from maintaining the integrity of nacre's brick‐and‐mortar nanoarchitecture, the biopolymer plays a critical role in the strengthening and toughening of nacre. By directly probing the biopolymer strands using atomic force microscopy, it is revealed that the biopolymer in nacre has the capability to strengthen itself during deformation. This remarkable deformation–strengthening mechanism contributes significantly to the ultrahigh toughness of nacre, and can be explained by a coiled‐spring model. The findings explain the mystery of nacre's toughening mechanisms, provide additional design guidelines for developing biomimetic nanomaterials, and lay a constitutive foundation for modeling the deformation behavior of nacre.