Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the inactivation of rat fatty acid synthase by C75: inhibition of partial reactions and protection by substrates.

C75, a synthetic inhibitor of FAS (fatty acid synthase), has both anti-tumour and anti-obesity properties. In this study we provide a detailed kinetic characterization of the mechanism of in vitro inhibition of rat liver FAS. At room temperature, C75 is a competitive irreversible inhibitor of the overall reaction with regard to all three substrates, i.e. acetyl-CoA, malonyl-CoA and NADPH, exhibiting pseudo-first-order kinetics of the complexing type, i.e. a weak non-covalent enzyme-inhibitor complex is formed before irreversible enzyme modification. C75 is a relatively inefficient inactivator of FAS, with a maximal rate of inactivation of 1 min(-1) and an extrapolated K(I) (dissociation constant for the initial complex) of approx. 16 mM. The apparent second-order rate constants calculated from these values are 0.06 mM(-1). min(-1) at room temperature and 0.21 mM(-1). min(-1) at 37 degrees C. We also provide experimental evidence that C75 inactivates the beta-ketoacyl synthase (3-oxoacyl synthase) partial activity of FAS. Unexpectedly, C75 also inactivates the enoyl reductase and thioesterase partial activities of FAS with about the same rates as for inactivation of the beta-ketoacyl synthase. In contrast with the overall reaction, the beta-ketoacyl synthase activity and the enoyl reductase activity, substrates do not protect the thioesterase activity of rat liver FAS from inactivation by C75. These results differentiate inactivation by C75 from that by cerulenin, which only inactivates the beta-ketoacyl synthase activity of FAS, by forming an adduct with an active-site cysteine. Interference by dithiothreitol and protection by the substrates, acetyl-CoA, malonyl-CoA and NADPH, further distinguish the mechanism of C75-mediated inactivation from that of cerulenin. The most likely explanation for the multiple effects observed with C75 on rat liver FAS and its partial reactions is that there are multiple sites of interaction between C75 and FAS.
CD28‐mediated activation in CD45RA+ and CD45RO+ T cells: enhanced levels of reactive oxygen intermediates and c‐Rel nuclear translocation in CD45RA+ cells

We have analyzed the effect of complete T cell activation (anti‐CD3 plus anti‐CD28) on the activation of NF‐κB in CD45RA+ (naive) and CD45RO+ (memory/effector) T cells. Long exposure (24 h) induced stronger NF‐κB DNA binding in CD45RA+ cells than in CD45RO+ cells. Analysis of the nuclear c‐Rel protein indicated that after anti‐CD3+anti‐CD28 stimulation the level of c‐Rel was higher in CD45RA+ cells. Analysis of the cytoplasmic inhibitor IκBα indicated that anti‐CD3+anti‐CD28 stimulation induced a long‐lasting degradation in CD45RA+ cells but in CD45RO+ cells the degradation process was more rapid. Because the CD28 costimulus is known to induce the production of reactive oxygen intermediates (ROIs), the intracellular ROI levels in CD45RA+ and CD45RO+ cells were compared by flow cytometry. ROIs were produced in both cell types, but more strongly in CD45RA+ cells. The data presented in this study further emphasize the differences between CD45RA+ and CD45RO+ T lymphocytes in ROI‐dependent signaling pathways. J. Leukoc. Biol. 63: 775–780; 1998.
NUCLEIC ACIDS OF CHLOROPLASTS AND MITOCHONDRIA IN SWISS CHARD

Nucleic acids in young leaves of Swiss chard have been studied by light and electron microscope techniques. Leaf DNA has also been characterized by density gradient centrifugation and shown to contain a minor band of higher guanine plus cytosine (GC) content, presumably attributable to chloroplasts. The chloroplasts were faintly stained by the Feulgen reaction; radioautography demonstrated the incorporation of tritiated thymidine in the cytoplasm and in some nuclei. The Feulgen stainability and most of the radioactivity were removable with DNase. Under the electron microscope, both mitochondria and chloroplasts were found to contain filamentous and particulate components within the matrix areas. The morphology of the filamentous component was dependent on the fixation, being partially clumped after OSO4 or formalin, but finely filamentous after Kellenberger fixation. The filaments were stainable with uranyl acetate, and were extractable with DNase following formalin fixation under conditions in which nuclear DNA was also extracted. The particulate component, after formalin fixation and uranyl staining, was prominent in chloroplasts from young leaves, but was only sparsely distributed in mitochondria. The stainability was removed with ribonuclease. We have concluded that chloroplasts and mitochondria of Swiss chard possess a filamentous component that contains DNA, probably responsible for both cytoplasmic thymidine incorporation and the minor band in CsCl centrifugation. A particulate ribosome-like component that contains RNA is also present.
International Nonprofit Collaboration

The importance and popularity of interorganizational collaboration among nongovernmental organizations (NGOs) have grown considerably in recent years. Despite these growths, however, not much is known about why NGOs network the way they do or why NGO networks are structured the way they are. Using homophily theory and exponential random graph modeling, this study examines the patterns of interorganizational collaborative ties among infectious diseases international NGOs (INGOs) in 2007 (n = 94). The results suggest that these NGOs are more likely to collaborate when they have the same status, when they have similar (closer) founding dates, when they are headquartered in the same global hemisphere (north/south), when they have common funding partners, and when they are headquartered in the same geographic regions. Overall, the findings from this study suggest that various sources of homophily inform partner selection among infectious disease INGOs.
Design of Algorithms for Bioinformatics

We provide a detailed review of basic algorithm techniqueues as applied to bioinformatic problems. Dynamic programming and graph algorithms are of particular concern due to their wide range of applications in bioinformatics. Some of the bioinformatic problems do not have solutions in polynomial time and are called NP-Complete. For these problems, approximation algorithms may be used. We show several examples where approximation algorithms may be used to provide sub-optimal solutions to these problems. We finally provide sample results of our ongoing work on building phylogenetic trees for Yhaplogroup data.
Mouse Matrix Metalloprotease‐1a (Mmp1a) Gives New Insight Into MMP Function

Matrix metalloprotease‐1 (MMP1) has been implicated in many human disease processes, however the lack of a well characterized murine homologue has significantly limited the study of MMP1 and the development of MMP‐targeted therapeutics. The discovery of murine Mmp1a in 2001, the functional mouse homologue of MMP1, offers a valuable tool for modeling MMP1‐mediated processes in mice. Variation in physiologic expression levels of Mmp1a in mice as compared to MMP1 in humans highlights the importance of understanding the similarities and differences between the homologues. Recent studies have demonstrated tumor growth‐, invasion‐, and angiogenesis‐promoting functions of Mmp1a in lung cancer models, consistent with the analogous functions observed for human MMP1. Biochemical investigations have shown that point mutations in the pro‐domain of mouse Mmp1a weaken docking between the pro‐ and catalytic domains, generating an unstable zymogen primed for activation. The difficulty to effectively maintain Mmp1a in the zymogen form may account for the tight control of Mmp1a expression and reduced expression in normal tissue as compared to inflammatory states or cancer. This discovery raises important questions about the activation mechanisms and regulation of the MMP family in general. J. Cell. Physiol. 229: 1875–1880, 2014. © 2014 Wiley Periodicals, Inc.
Exploitation of the Low Fidelity of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase and the Nucleotide Composition Bias in the HIV-1 Genome To Alter the Drug Resistance Development of HIV

ABSTRACT The RNA genome of the lentivirus human immunodeficiency virus type 1 (HIV-1) is significantly richer in adenine nucleotides than the statistically equal distribution of the four different nucleotides that is expected. This compositional bias may be due to the guanine-to-adenine (G→A) nucleotide hypermutation of the HIV genome, which has been explained by dCTP pool imbalances during reverse transcription. The adenine nucleotide bias together with the poor fidelity of HIV-1 reverse transcriptase markedly enhances the genetic variation of HIV and may be responsible for the rapid emergence of drug-resistant HIV-1 strains. We have now attempted to counteract the normal mutational pattern of HIV-1 in response to anti-HIV-1 drugs by altering the endogenous deoxynucleoside triphosphate pool ratios with antimetabolites in virus-infected cell cultures. We showed that administration of these antimetabolic compounds resulted in an altered drug resistance pattern due to the reversal of the predominant mutational flow of HIV (G→A) to an adenine-to-guanine (A→G) nucleotide pattern in the intact HIV-1-infected lymphocyte cultures. Forcing the virus to change its inherent nucleotide bias may lead to better control of viral drug resistance development.
Coherence Miss Classification for Performance Debugging in Multi-Core Processors Guru

Multi-core processors offer large performance potential for parallel applications, but writing these applications is notoriously difficult. Tuning a parallel application to achieve scalability, referred to as performance debugging, is often more challenging for programmers than conventional debugging for correctness. Parallel programs have several performance related issues that are not seen in sequential programs. In particular, increased cache misses triggered by data sharing (coherence misses) are a challenge for programmers. Data sharing misses can stem from true or false sharing and the solutions for the two types of misses are quite different. Therefore, to minimize coherence misses, it is not just sufficient for programmers to only identify the source of the extra misses. They should also have information about the type of coherence misses that are hurting performance. In this paper, we propose a programmer-centric definition of false sharing misses for use in performance debugging. We describe our algorithm to classify coherence misses based on this definition, and explore a practical and low cost solution that keeps no state at all. We find that the low cost solution can suffer from considerable inaccuracy that might mislead programmers in their performance debugging efforts.
Extended Ambient Term

Abstract The ambient term in a renderer is a constant color added to all points yielding a crude global approximation to indirect lighting. Because the ambient term ignores geometric occlusion conditions, it is computationally inexpensive. We present an extended ambient term that provides better results than the constant term but is still inexpensive, because it also does not compute occlusion conditions. It is based on the idea of finding a six-sided axis-aligned environment which is similar in color and area to the real scene, and deriving an approximation to indirect lighting by computing interreflections in the simplified scene.
RECOGNIZING INTERACTIONS BETWEEN HUMAN AND OBJECT BASED ON SOCIAL NETWORK ANALYSIS

Recognizing human-object interactions in videos is a very challenging problem in computer vision research. There are two major difficulties lying in this task: (1) The detection o f human body parts and objects is usually affected by the quality of the videos, for instance, low resolutions of the video s, camera motions, and blurring frames caused by fast motions, as well as the self-occlusions during human-object interac tions. (2) The spatial and temporal dynamics of human-objec t interaction are hard to model. In order to overcome those nat ural obstacles, we propose a new method using social network analysis (SNA) based features to describe the distribu tions and relationships of low level objects for human-obje ct interaction recognition. In this approach, the detected hu man body parts and objects are treated as nodes in social network graphs, and a set of SNA features including closeness, centrality and centrality with relative velocity are extracted for action recognition. A major advantage of SNA based feature set is its robustness to varying node numbers and erroneous node detections, which are very common in humanobject interactions. An SNA feature vector will be extracte d for each frame and different human-object interactions are classified based on these features. Two classification methods, including Support Vector Machine (SVM) and Hidden Markov Model (HMM), have been used to evaluate the proposed feature set on four different human-object interacti ons from HMDB dataset [1]. The experimental results demonstrated that the proposed framework can effectively captur e the dynamical characteristics of human-object interactio n and outperforms the state of art methods in human-object intera ction recognition.
Musical Ratios in Sounds from the Human Cochlea

The physiological roots of music perception are a matter of long-lasting debate. Recently light on this problem has been shed by the study of otoacoustic emissions (OAEs), which are weak sounds generated by the inner ear following acoustic stimulation and, sometimes, even spontaneously. In the present study, a high-resolution time–frequency method called matching pursuit was applied to the OAEs recorded from the ears of 45 normal volunteers so that the component frequencies, amplitudes, latencies, and time-spans could be accurately determined. The method allowed us to find that, for each ear, the OAEs consisted of characteristic frequency patterns that we call resonant modes. Here we demonstrate that, on average, the frequency ratios of the resonant modes from all the cochleas studied possessed small integer ratios. The ratios are the same as those found by Pythagoras as being most musically pleasant and which form the basis of the Just tuning system. The statistical significance of the results was verified against a random distribution of ratios. As an explanatory model, there are attractive features in a recent theory that represents the cochlea as a surface acoustic wave resonator; in this situation the spacing between the rows of hearing receptors can create resonant cavities of defined lengths. By adjusting the geometry and the lengths of the resonant cavities, it is possible to generate the preferred frequency ratios we have found here. We conclude that musical perception might be related to specific geometrical and physiological properties of the cochlea.
Learning of Fuzzy Cognitive Maps With Varying Densities Using A Multiobjective Evolutionary Algorithm

Fuzzy cognitive maps (FCMs) are cognition fuzzy influence graphs, which are based on fuzzy logic and neural networks. Many automated learning algorithms have been proposed to reconstruct FCMs from data, but most learned maps using such methods are much denser than those constructed by human experts. To this end, we first model the FCM learning problem as a multiobjective optimization problem, and then propose a multiobjective evolutionary algorithm, labeled as MOEA-FCM, to learn FCM models. MOEA-FCM is able to learn FCMs with varying densities at the same time from input historical data, which can provide candidate solutions with different properties for decision makers. In the experiments, the performance of MOEA-FCM is validated on both synthetic and real data with varying sizes and densities. The experimental results demonstrate the efficiency of MOEA-FCM and show that MOEA-FCM can not only reconstruct FCMs with high accuracy without expert knowledge, but also create a diverse Pareto optimal front which consists of FCMs with varying densities. The significance of this study is that decision makers can choose different FCM models provided by MOEA-FCM based on their practical requirements.
The ‘other’ Europeans: the semiotic imperative of style in Euro Visions by Magnum Photos

In this article, the author examines Euro Visions, the exhibition created by Magnum Photos to portray the new countries that joined the European Union in 2004 and 2007. She begins by observing that this project’s deviations from the world-leading agency’s trademark humanist style of photography were discursively ascribed to Euro Visions photographers’ authorial style. In this regard, she identifies two key semiotic resources – typing and juxtaposition – that were mobilized as markers of individual style. She then argues that both typing and juxtaposition should instead be seen as generic semiotic resources rooted in corporate styles of visual communication, which contribute to othering the ‘new’ Europeans. She also argues that in Euro Visions, the notion of ‘distinctive’ authorial style was deployed as symbolic currency for a global(ist) market that rewards cultural production and, broadly, aestheticization. She finally posits that, in projects like Euro Visions, what is mostly (generic) design may get passed off as (specific) representation, and that this aestheticization of styles and identities may be mystified as the substantial honouring of difference and diversity.
Therapeutic Discovery High-Throughput Screen Identifies Novel Inhibitors of Cancer Biomarker a-Methylacyl Coenzyme A Racemase ( AMACR / P 504 S )

a-methylacyl coenzyme A racemase (AMACR) is a metabolic enzyme whose overexpression has been shown to be a diagnostic indicator of prostatic adenocarcinoma and other solid tumors. Here, we confirm that attenuation of AMACR expression diminishes the growth of prostate cancer cell lines by using stably expressed short-hairpin RNA constructs. This observation strongly suggests that the AMACR enzymemay be a target for therapeutic inhibition in prostate cancer. To this end, we report here a novel assay capable of screening libraries of diverse small molecules for inhibitors of AMACR activity. This assay facilitated the screening of approximately 5,000 unique compounds and the discovery of 7 distinct chemical entities capable of inhibiting AMACR at low micromolar concentrations. The most potent inhibitor discovered is the selenoorganic compound ebselen oxide [inhibitory concentration (IC50): 0.80 mmol/L]. The parent compound, ebselen (IC50: 2.79 mmol/L), is a covalent inactivator of AMACR (KI(inact): 24 mmol/L). Two of the AMACR inhibitors are selectively toxic to prostate cancer cell lines (LAPC4/LNCaP/PC3) that express AMACR compared to a normal prostate fibroblast cell line (WPMY1) that does not express the protein. This report shows the first high-throughput screen for the discovery of novel AMACR inhibitors, characterizes the first nonsubstrate-based inhibitors, and validates that AMACR is a viable chemotherapeutic target in vitro. Mol Cancer Ther; 10(5); 825–38. 2011 AACR.
Comparison of Three Pulpotomy Agents in Primary Molars: A Randomised Clinical Trial

INTRODUCTION Pulpotomy is an accepted treatment for the management of cariously exposed pulps in symptom free primary molars. The purpose of this study was to compare the clinical and radiological outcomes of three different single-visit vital pulp therapies including pulpotomy with electrosurgery (ES), formocresol (FC) and ferric sulfate (FS) in cariously exposed primary molar teeth. MATERIALS AND METHODS Seventy-six patients, 5-10 years old, were enrolled in this clinical investigation. One primary molar tooth of each patient was selected for this study. Samples were randomly divided into three groups. Teeth were treated with FC in group 1 (i.e. control group) (n=24), FS in group 2 (n=28), and ES in group 3 (n=24) using standardized pulpotomy procedures. All treated teeth were clinically and radiographically evaluated after 6 and 9 months. Statistical analysis was performed using Fishers exact test. RESULTS The overall success rate in groups 1, 2 and 3 was 87.5%, 82.1% and 83.3%, respectively. Favorable clinical and radiological success rates of FS and ES pulpotomy was observed which was comparable to FC. CONCLUSION FS and ES can be considered alternative materials for the pulpotomy of primary molars.
Ab initio simulations of geometrical frustration in supercooled liquid Fe and Fe-based metallic glass

We investigate short range order in liquid and supercooled liquid Fe and Fe-based metallic glass using ab initio simulation methods. We analyze the data to quantify the degree of local icosahedral and polytetrahedral order and to understand the role of alloying in controlling the degree of geometric frustration. Comparing elemental Fe to Cu P. Ganesh and M. Widom, Phys. Rev. B 74, 134205 2006 we find that the degree of icosahedral order is greater in Fe than in Cu, possibly because icosahedral disclination line defects are more easily incorporated into bcc environments than fcc. In Fe-based metallic glass-forming alloys FeB and FeZrB we find that introducing small concentrations of small B atoms and large Zr atoms controls the frustration of local icosahedral order.
APPROXIMATION IN ALGORITHMIC GAME THEORY : ROBUST APPROXIMATION BOUNDS FOR EQUILIBRIA AND AUCTIONS

1.1. Motivation. Many modern computer science applications involve autonomous, self-interested agents. It is therefore important for us to consider agents' strategic behavior in modelling the problems, where non-cooperative game theory can be very helpful. Unfortunately, as one can expect, strategic behavior of the agents often make full optimality di cult or impossible for various reasons. Three common reasons are the following:
Phytochemical Constituens of Cirsium setidens Nakai and Their Cytotoxicity against Human Cancer Cell Lines

Five terpenes (1-5), three fatty acids (6-8), two sterols (9 and 11), and a monogalactosyldiacyl glycerol (10) were isolated from the methylene chloride extract of the aerial part of Cirslum setidens. Their chemical structures were determined to be (z-tocopherol (1), 25-hydroperoxycycloart-23-en-3~-ol (2), 24-hydroperoxycycloart-25-en-3~-ol (3), mokko lactone (4), transphytol (5), 9, 12, 15-octadecatrienoic acid (6), 9, 12-octadecadienoic acid (7), hexadecanoic acid (8), acylglycosyl [3-sitosterol (9), (2R)-1, 2-O-(9z, 12z, 15z-dioctadecatrienoyl)-3-O-13-Dgalactopyranosyl glycerol (10) and ~-sitosterol glucoside (11) by spectral evidences. Compound 3 exhibited significant cytotoxic activity against five human cancer cell lines with its EDs0 values ranging from 2.66 to 11.25 ~M.
Determination of cyanidin-3-glucoside (red kernel food colour) in beverages by high performance liquid chromatography and a study of its degradation by quadruple time-of-flight mass spectrometry

A method for the determination of cyanidin-3-glucoside (red kernel colour, RKC) in various matrices, including carbonated soft drinks, fruit-based soft drinks, sugar confectionery and milk-based drinks, by high performance liquid chromatography (HPLC) based on UV–Vis detection (at 520 nm) have been developed. Pre-treatment procedures for various matrices have been optimised. For soft drinks, the pH values were adjusted to 2.0, and sugar confectionery and milk-based drinks were extracted with 30 and 50% methanol in 0.1% formic acid (pH ∼ 2.5) aqueous solutions, respectively. The limits of detection for the established methods ranged from 0.2 mg/kg for soft drinks to 2.0 mg/kg for the sugar confectionery and milk-based drinks with the relative standard deviations lower than 7%, which satisfy the method performance requirements for quality control for the beverages. The stability of the colourant RKC under various thermal and pH conditions was investigated by quadruple time-of-flight mass spectrometry (Q-TOF-MS). The main colourant component of RKC, cyanidin-3-glucoside (Cyd-3-Glu), lost the glucose entity under thermal treatment. A new component was identified when RKC degraded under various pH conditions and a degradation pathway is proposed. The results will assist in understanding the degradation mechanism of the colourant Cyd-3-Glu.