Miracle-dz/UniFAR-FTUs huggingface dataset:
Product-Line Extensions and Pricing Strategies of Brand-Name Drugs Facing Patent Expiration

OBJECTIVES: This study proposed an alternative to brand loyalty as the explanation for the continued price rigidity of patent-expired brand-name prescription drugs despite the increase in market entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act. Study hypotheses were to test (1) whether market entries of new-product extensions are associated with market success of original brand-name drugs before generic drug entry, and (2) whether original brand-name drugs exhibit price rigidity to generic entry only when they are extended. METHODS: The design is a retrospective follow-up study for the prescription drug brands that lost their patents between 1987 and 1992. The drug brands were limited to nonantibiotic, orally administered drugs containing only 1 active pharmaceutical ingredient. Information on patent expiration, entry of a product extension, and market success were determined from the U.S. Food and Drug Administrations Orange Book, First DataBank, and American Druggist, respectively. Market success was defined as whether an original drug brand was listed in the top 100 prescriptions most frequently dispensed before facing generic entry. Product-line extension was defined as the appearance of another product that a company introduces within the same market after its existing product. Drug prices were average wholesale prices from the Drug Topics Red Book. The relationship between product-line extension and market success was examined using a logistic regression analysis. The price rigidity to entry was tested using a panel regression analysis. RESULTS: A total of 27 drug brands lost their patents between 1987 and 1992. Drug brands that achieved market success were 16 times more likely to be extended than were those that did not (OR=16, 95% confidence interval, 2.12-120.65). The price rigidity to entry existed in drug brands with extensions (b=2.65%, P less than 0.033), but not in those brands without extensions (b=-2.40%, P less than 0.001). CONCLUSIONS: This study provided some support for the alternative explanation to brand loyalty that a new product-line extension introduced for an original brand helps the original price be rigid despite the entry of generic drugs facilitated by the 1984 Drug Price Competition and Patent Term Restoration Act.
Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity

The present study was undertaken to gain insights into the mechanism of cell cycle arrest caused by honokiol, a constituent of oriental herb Magnolia officinalis. The honokiol treatment decreased the viability of PC-3 and LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which correlated with G0-G1 phase cell cycle arrest. The honokiol-mediated cell cycle arrest was associated with a decrease in protein levels of cyclin D1, cyclin-dependent kinase 4 (Cdk4), Cdk6, and/or cyclin E and suppression of complex formation between cyclin D1 and Cdk4 as revealed by immunoprecipitation using anti–cyclin D1 antibody followed by immunoblotting for Cdk4 protein. The honokiol-treated PC-3 and LNCaP cells exhibited a marked decrease in the levels of total and phosphorylated retinoblastoma protein (Rb), which correlated with the suppression of transcriptional activity of E2F1. Exposure of PC-3 and LNCaP cells to honokiol resulted in the induction of p21 (PC-3 and LNCaP) and p53 protein expression (LNCaP). However, small interfering RNA (siRNA)–mediated knockdown of either p21 (PC-3 and LNCaP) or p53 (LNCaP) protein failed to confer any protection against honokiol-induced cell cycle arrest. The honokiol treatment caused the generation of reactive oxygen species (ROS), and the cell cycle arrest caused by honokiol was partially but significantly attenuated in the presence of antioxidant N-acetylcysteine. In conclusion, the present study reveals that the honokiol-mediated G0-G1 phase cell cycle arrest in human prostate cancer cells is associated with the suppression of protein level/phosphorylation of Rb leading to inhibition of transcriptional activity of E2F1. [Mol Cancer Ther 2007;6(10):2686–95]
Experimental and Atomic Modeling of the Adsorption of Acid Azo Dye 57 to Sepiolite

Sepiolite is a hydrated magnesium silicate with a microporous and mesoporous structure. The fibrous morphology and the alternating blocks and tunnels along the fiber direction of sepiolite make it an ideal material to sequester a variety of organic and inorganic contaminants. The adsorption of various surfactants by organo sepiolites have been experimentally investigated. How this hydrophobic material adsorbs dye molecules at the atomic level, however, is a great mystery. For this reason, the present study focused on the adsorption of acid azo 57 dye molecules to modified sepiolite. For this purpose, the amenability of sepiolite to remove the anionic textile dye (acid azo red dye 57) was first studied in detail. Additionally, a typical cationic surfactant, hexadecyltrimethylammonium Br (HTAB), was used to modify sepiolite to increase the adsorption capacity. Zeta potential measurements on the sepiolite and the HTAB modified sepiolite were also carried out. Moreover, Density Functional Theory (DFT) studies were performed to understand the mechanism of the adsorption of dye molecules to natural and modified sepiolite surfaces. On the basis of the experimental studies, three general systems were theoretically examined: (i) HTAB molecules on sepiolite basal surfaces to represent four Si tetrahedra, (ii) neutral or charged acid azo red dye 57 molecules on sepiolite basal surfaces to represent four Si tetrahedra, and (iii) HTAB on the surface of neutral or charged acid azo red dye 57 molecules as a substrate. The results clearly indicated good agreement between the experimental studies and the theoretical computational DFT studies. For example, the double layer structure found in experimental studies was also demonstrated in DFT studies and confirmed increased adsorption in the presence of acid azo dye 57.
Efficient sentence segmentation using syntactic features

To enable downstream language processing,automatic speech recognition output must be segmented into its individual sentences. Previous sentence segmentation systems have typically been very local,using low-level prosodic and lexical features to independently decide whether or not to segment at each word boundary position. In this work,we leverage global syntactic information from a syntactic parser, which is better able to capture long distance dependencies. While some previous work has included syntactic features, ours is the first to do so in a tractable, lattice-based way, which is crucial for scaling up to long-sentence contexts. Specifically, an initial hypothesis lattice is constructed using local features. Candidate sentences are then assigned syntactic language model scores. These global syntactic scores are combined with local low-level scores in a log-linear model. The resulting system significantly outperforms the most popular long-span model for sentence segmentation (the hidden event language model) on both reference text and automatic speech recognizer output from news broadcasts.
Classification of Canine Malignant Lymphomas According to the World Health Organization Criteria

A study was carried out to test the accuracy and consistency of veterinary pathologists, not specialists in hematopathology, in applying the World Health Organization (WHO) system of classification of canine lymphomas. This study represents an initiative of the ACVP Oncology Committee, and the classification has been endorsed by the World Small Animal Veterinary Association (WASVA). Tissue biopsies from cases of canine lymphoma were received from veterinary oncologists, and a study by pathologists given only signalment was carried out on 300 cases. Twenty pathologists reviewed these 300 cases with each required to choose a diagnosis from a list of 43 B and T cell lymphomas. Three of the 20 were hematopathologists who determined the consensus diagnosis for each case. The 17 who formed the test group were experienced but not specialists in hematopathology, and most were diplomates of the American or European Colleges of Veterinary Pathology. The overall accuracy of the 17 pathologists on the 300 cases was 83%. When the analysis was limited to the 6 most common diagnoses, containing 80% of all cases, accuracy rose to 87%. In a test of reproducibility enabled by reintroducing 5% of cases entered under a different identity, the overall agreement between the first and second diagnosis ranged from 40 to 87%. The statistical review included 43,000 data points for each of the 20 pathologists.
On oblivious PTAS's for nash equilibrium

If a class of games is known to have a Nash equilibrium with probability values that are either zero or Ω(1) -- and thus with support of bounded size -- then obviously this equilibrium can be found exhaustively in polynomial time. Somewhat surprisingly, we show that there is a PTAS for the class of games whose equilibria are guaranteed to have small --- O(1/n) -- values, and therefore large -- Ω(n) -- supports. We also point out that there is a PTAS for games with sparse payoff matrices, a family for which the exact problem is known to be PPAD-complete [Chen, Deng, Teng 2006]. Both algorithms are of a special kind that we call oblivious: The algorithm just samples a fixed distribution on pairs of mixed strategies, and the game is only used to determine whether the sampled strategies comprise an ε-Nash equilibrium; the answer is "yes" with inverse polynomial probability (in the second case, the algorithm is actually deterministic). These results bring about the question: Is there an oblivious PTAS for finding a Nash equilibrium in general games? We answer this question in the negative; our lower bound comes close to the quasi-polynomial upper bound of [Lipton, Markakis, Mehta 2003]. Another recent PTAS for anonymous games [Daskalakis, Papadimitriou 2007 and 2008, Daskalakis 2008] is also oblivious in a weaker sense appropriate for this class of games (it samples from a fixed distribution on unordered collections of mixed strategies), but its running time is exponential in 1/ε. We prove that any oblivious PTAS for anonymous games with two strategies and three player types must have 1/εα in the exponent of the running time for some α ≥ 1/3, rendering the algorithm in [Daskalakis 2008] (which works with any bounded number of player types) essentially optimal within oblivious algorithms. In contrast, we devise a poly n • (1/ε)O(\log2(1/ε)) non-oblivious PTAS for anonymous games with two strategies and any bounded number of player types. The key idea of our algorithm is to search not over unordered sets of mixed strategies, but over a carefully crafted set of collections of the first O(log 1/ε) moments of the distribution of the number of players playing strategy 1 at equilibrium. The algorithm works because of a probabilistic result of more general interest that we prove: the total variation distance between two sums of independent indicator random variables decreases exponentially with the number of moments of the two sums that are equal, independent of the number of indicators.
A dummy-based anonymization method based on user trajectory with pauses

A variety of services utilizing users' positions have become available because of rapid advances in Global Positioning System (GPS) technologies. Since location information may reveal private information, preserving location privacy has become a significant issue. We proposed a dummy-based method of anonymizing location to protect this privacy in our previous work that generated dummies based on various restrictions in a real environment. However, the previous work assumed a simplified mobility model in which users kept moving and did not stop. If we assume a more realistic mobility model in which users often pause to visit various attractions, it becomes increasingly more difficult to generate dummies that will move naturally. In this paper, we assumed that the users' movements are known in advance and propose a dummy-based anonymization method based on user movements, where dummies move naturally while stopping at several locations. We simulated user movements on real map information and verified the method we propose was more effective than the previous one.
Plasma Neutrophil Gelatinase-Associated Lipocalinin in the General Population: Association With Inflammation and Prognosis

Objective— Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited. Approach and Results— We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. Conclusions— Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.
A computational method for studying the relation between alternative splicing and DNA methylation

Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non-trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large-scale data sets.
Cancer stem cells and tumor metastasis

Previous studies have shown that tumors can induce angiogenesis and lymphangiogenesis, which plays an important role in promoting hematogenous and lymphogenous spread. In recent years, the cancer stem cell (CSC) theory has emerged as an attractive hypothesis for tumor development and progression. The theory proposes that one small subset of cancer cells has the characteristics of stem cells. These CSCs have the capability of both self-renewal and differentiation into diverse cancer cells, which play a decisive role in maintaining capacity for malignant proliferation, invasion, metastasis, and tumor recurrence. CSCs are involved in tumor metastasis, however, the details, and the possible relationship of CSCs, angiogenesis, lymphangiogenesis, and tumor metastasis is still ambiguous. The aim of this report is to summarize current studies of CSCs and tumor metastasis at the cellular level, with the goal of bringing new insights into understanding the role of CSCs in tumor metastasis.
Novel Approach to Real Polynomial Root-finding and Matrix Eigen-solving

Univariate polynomial root-finding is both classical and important for modern computing. Frequently one seeks just the real roots of a polynomial with real coefficients. They can be approximated at a low computational cost if the polynomial has no nonreal roots, but typically nonreal roots are much more numerous than the real ones. We dramatically accelerate the known algorithms in this case by exploiting the correlation between the computations with matrices and polynomials, extending the techniques of the matrix sign iteration, and exploiting the structure of the companion matrix of the input polynomial. We extend some of the proposed techniques to the approximation of the real eigenvalues of a real nonsymmetric matrix.
Bodily selves in relation: embodied simulation as second-person perspective on intersubjectivity

This article addresses basic aspects of social cognition focusing on the pivotal role played by the lived body in the constitution of our experience of others. It is suggested that before studying intersubjectivity we should better qualify the notion of the self. A minimal notion of the self, the bodily self, defined in terms of its motor potentialities, is proposed. The discovery of mirror mechanisms for action, emotions and sensations led to the proposal of an embodied approach to intersubjectivity—embodied simulation (ES) theory. ES and the related notion of neural reuse provide a new empirically based perspective on intersubjectivity, viewed first and foremost as intercorporeality. ES challenges the notion that folk psychology is the sole account of interpersonal understanding. ES is discussed within a second-person perspective on mindreading.
Comparison of cyanobacterial bio-fertilizer with urea on three crops and two soils of Ethiopia

Although chemical fertilizers have long been used to meet the high demand of nitrogen (N), the most common limiting nutrient to plant growth, the frequent use of this fertilizer gradually deteriorates soil fertility in addition to its high cost, lower supply and agronomic use efficiency in Ethiopia. Nevertheless, N-fixing cyanobacterial biofertilizers are eco-friendly, and currently considered important to support the developing organic agriculture. Therefore, this study was conducted to evaluate the potential of cyanobacterial biofertilizer for the growth and yield of three commonly growing crops in Ethiopia: maize, kale, and pepper under Alfisol and Andosol, and to investigate the potential contribution of cyanobacteria biofertilizer in selected soil fertility parameters. Three independent factorial experiments were conducted simultaneously in the greenhouse. Each experiment included a factorial combination of four nitrogen fertilizer sources applied at recommendation rate for each crop (control, urea, dried cyanobacteria, and liquid cyanobacteria,) and two soil types with acidic and alkaline pH (Alfisols and Andosols, respectively) arranged in a complete randomized design (CRD) with three replications. Application of dried and liquid cyanobacterial biofertilizer treatments significantly improves the soil N, soil organic carbon (SOC) and available P, Fe and Zn. Cyanobacteria treatments were also found to reduce or maintain the mean soil pH. Accordingly, maximum values of all the vegetative growth attributes of kale, and maize were obtained from the application of two comparable-fertilizer treatments: air-dried cyanobacteria and urea while for pepper crops only dried cyanobacteria. Concentrations of N, P, Zn, and Fe in leaves of kale, pepper, and maize were also significantly increased by air-dried cyanobacterial biofertilizer. Overall, dried cyanobacteria improved the growth and yield of the three crops, and the fertility of the soils. Therefore, the use of dry cyanobacterial biofertilizer could be recommended as a supplementary N source to inorganic fertilizer for kale, pepper and maize production in both study sites. Key words: Alfisols, andosols, biofertilizers, cyanobacteria, N-fixing.
Diacritics restoration for Arabic dialect texts

In this paper we present a statistical approach for automatic diacritization of Algiers dialectal texts. This approach is based on statistical machine translation. We first investigate this approach on Modern Standard Arabic (MSA) texts using several data sources and extrapolated the results on available dialectal texts. For evaluation we used word and diacritization error rates and also precision and recall. Index Terms: Machine translation system, Modern Standard Arabic, automatic diacritization, Algiers’s dialect.
Secondary Traumatic Stress in Oncology Staff

As empathetic caregivers, oncology staff may be prone to secondary traumatic stress (STS). Secondary traumatic stress results from exposure to persons who have experienced trauma and from giving care to such persons. The presence of STS among oncology staff has not been documented. This correlational descriptive study examined STS among oncology staff at a 500-bed Magnet-designated community hospital by determining the presence of individual symptoms and frequency with which diagnostic criteria for STS are met. Also determined were associations between STS demographic characteristics and specific stress-reduction activities. In this study, 43 staff members from an inpatient oncology unit completed mailed surveys. The Secondary Traumatic Stress Scale assessed the frequency of intrusion, avoidance, and arousal symptoms associated with STS; also assessed were use/helpfulness of stress-reduction activities. In this first study to document the prevalence of STS among oncology staff, prevalence ranged from 16% (Bride's method) to 37% (cutoff-score method). Most common symptoms were difficulty sleeping, intrusive thoughts about patients, and irritability. Least common were avoidance of people, places, and things and disturbing dreams about patients. Current use of massage was significantly predictive of not having STS. Ethnicity of staff member was related to having STS. Further research is warranted evaluating STS prevalence in different groups of oncology staff along with the effect of STS on burnout and job retention.