Miracle-dz/UniFAR-FTUs huggingface dataset:
Purines inhibit poly(ADP‐ribose) polymerase activation and modulate oxidant‐induced cell death

Purines such as adenosine, inosine, and hypoxanthine are known to have potent antiinflammatory effects. These effects generally are believed to be mediated by cell surface adenosine receptors. Here we provide evidence that purines protect against oxidant‐induced cell injury by inhibiting the activation of the nuclear enzyme poly(ADP‐ribose) polymerase (PARP). Upon binding to broken DNA, PARP cleaves NAD+ into nicotinamide and ADP‐ribose and polymerizes the latter on nuclear acceptor proteins such as histones and PARP itself. Overactivation of PARP depletes cellular NAD+ and ATP stores and causes necrotic cell death. We have identified some purines (hypoxanthine, inosine, and adenosine) as potential endogenous PARP inhibitors. We have found that purines (hypoxanthine > inosine > adenosine) dose dependently inhibited PARP activation in peroxynitritetreated macrophages and also inhibited the activity of the purified PARP enzyme. Consistently with their PARP inhibitory effects, the purines also protected interferon γ + endotoxin (IFN/LPS) ‐stimulated RAW macrophages from the inhibition of mitochondrial respiration and inhibited nitrite production from IFN/LPS‐stimulated macrophages. We have selected hypoxanthine as the most potent cytoprotective agent and PARP inhibitor among the three purine compounds, and investigated the mechanism of its cytoprotective effect. We have found that hypoxanthine protects thymocytes from death induced by the cytotoxic oxidant peroxynitrite. In line with the PARP inhibitory effect of purines, hypoxanthine has prevented necrotic cell death while increasing caspase activity and DNA fragmentation. As previously shown with other PARP inhibitors, hypoxanthine acted proximal to mitochondrial alterations as hypoxanthine inhibited the peroxynitrite‐induced mitochondrial depolarization and secondary superoxide production. Our data imply that purines may serve as endogenous PARP inhibitors. We propose that, by affecting PARP activation, purines may modulate the pattern of cell death during shock, inflammation, and reperfusion injury. —Virág, L. , Szabó, C. Purines inhibit poly(ADP‐ribose) polymerase activation and modulate oxidant‐induced cell death. FASEB J. 15, 99–107 (2001)
Cytokine responses to treadmill running in healthy and illness-prone athletes.

PURPOSE To characterize differences in cytokine responses to exercise of different intensities and durations between healthy and illness-prone runners. METHODS Trained distance runners were classified as healthy (no more than two episodes of upper-respiratory symptoms per year; N = 10) or illness-prone (four or more episodes per year; N = 8) and completed three treadmill tests: SHORT (30 min, 65% VO2max), LONG (60 min, 65% VO2max), and INTENSE (6 x 3 min, 90% VO2max). Blood samples were collected pre-, post-, 1 h, 10 h, and 24 h after exercise, and interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, and IL-1ra concentrations were determined. Repeated-measures ANOVA was used to assess changes in cytokine responses to exercise. Magnitudes of changes and differences between groups were characterized using Cohen's effect size (ES) criteria. RESULTS Resting IL-8, IL-10, and IL-1ra concentrations were 19-38% lower (ES:0.38-0.96; small to moderate differences) in illness-prone runners. Similarly, postexercise IL-10 concentrations were 13-20% lower (ES: 0.20-0.37; small differences), and IL-1ra concentrations were 10-20% lower (ES: 0.22-0.38; small differences) in illness-prone subjects. In contrast, IL-6 elevations were 84-185% higher (ES: 0.29-0.59, small differences) in illness-prone subjects. Postexercise responses of IL-2, IL-4, and IL-12 were small and not substantially different between the groups. CONCLUSIONS Cytokine responses to controlled treadmill running differ between healthy and illness-prone athletes. Illness-prone distance runners showed evidence suggestive of impaired inflammatory regulation in the hours after exercise that may account for the greater frequency of upper-respiratory symptoms experienced.
BeamECOC: A local search for the optimization of the ECOC matrix

Error Correcting Output Coding (ECOC) is a multi-class classification technique in which multiple binary classifiers are trained according to a preset code matrix such that each one learns a separate dichotomy of the classes. While ECOC is one of the best solutions for multi-class problems, one issue which makes it suboptimal is that the training of the base classifiers is done independently of the generation of the code matrix.
Archaeological Evidence for Occupational Specialization Among the Classic Period Maya at Tikal, Guatemala

Abstract Recent models for the organization of Classic period Maya in the Guatemala lowlands suggest a complex system of stratified social classes. Much of the basic data supporting such theoretical models is derived from the evidence for the existence of numerous occupational specializations. Previously, the data have been largely inferential, but extensive and comprehensive excavations at Tikal over a period of 13 yr have provided significant information suggesting that the occupations of residents of specific buildings or house groups can be determined. This evidence also suggests techniques by which future excavations might be directed in order to augment existing information.
Evolutionary data purification for social media classification

We present a novel algorithm for the semantic labeling of photographs shared via social media. Such imagery is diverse, exhibiting high intra-class variation that demands large training data volumes to learn representative classifiers. Unfortunately image annotation at scale is noisy resulting in errors in the training corpus that confound classifier accuracy. We show how evolutionary algorithms may be applied to select a 'purified' subset of the training corpus to optimize classifier performance. We demonstrate our approach over a variety of image descriptors (including deeply learned features) and support vector machines.
Beam Steering for Electromagnetic Vortex Imaging Using Uniform Circular Arrays

The electromagnetic waves carrying orbital angular momentum can achieve azimuthal resolution for radar imaging without relative motion. However, the difference of main-lobe direction of different modes limits the echo energy. In this letter, the beam steering for vortex beams generated by a uniform circular array is performed by phased array technology. The main lobes of vortex beams carrying different modes can illuminate the target area with this method. The radiation field after beam steering is derived, and the phase distribution is thoroughly investigated. Then, the imaging model is established, and $l_p$ regularized least-squares algorithm is employed to reconstruct the two-dimensional target image. Simulation results demonstrate the effectiveness of the proposed beam steering method and that higher resolution can be achieved than Fourier transform method.
Flexibility of the Kir6.2 inward rectifier K+ channel pore

Interactions of sulfhydryl reagents with introduced cysteines in the pore-forming (Kir6.2) subunits of the KATP channel were examined. 2-Aminoethyl methanethiosulfonate (MTSEA+) failed to modify Cd2+-insensitive control-Kir6.2 channels, but rapidly and irreversibly modified Kir6.2[L164C] (L164C) channels. Although a single Cd2+ ion is coordinated by L164C, four MTSEA+ “hits” can occur, each sequentially reducing the single-channel current. A dimeric fusion of control-Kir6.2 and L164C subunits generates Cd2+-insensitive channels, confirming that at least three cysteines are required for coordination, but MTSEA+ modification of the dimer occurs in two hits. L164C channels were not modified by bromotrimethyl ammoniumbimane (qBBr+), even though qBBr+ caused voltage-dependent block (as opposed to modification) that was comparable to that of MTSEA+ or 3-(triethylammonium)propyl methanethiosulfonate (MTSPTrEA+), implying that qBBr+ can also enter the inner cavity but does not modify L164C residues. The Kir channel pore structure was modeled by homology with the KcsA crystal structure. A stable conformation optimally places the four L164C side chains for coordination of a single Cd2+ ion. Modification of these cysteines by up to four MTSEA+ (or three MTSPTrEA+, or two qBBr+) does not require widening of the cavity to accommodate the derivatives within it. However, like the KcsA crystal structure, the energy-minimized model shows a narrowing at the inner entrance, and in the Kir6.2 model this narrowing excludes all ions. To allow entry of ions as large as MTSPTrEA+ or qBBr+, the entrance must widen to >8 Å, but this widening is readily accomplished by minimal M2 helix motion and side-chain rearrangement.
The impact of gender on early ill-health retirement in people with heart disease and depression

Objective: Depression and heart disease are major causes of early ill-health retirement. The effect of comorbid depression on the award of ill-health retirement in those with heart disease is unclear, however, and may differ by gender. Given the deleterious effects of ill-health retirement, identifying at-risk groups is important for guiding targeted interventions. Method: We retrospectively analysed baseline data of 20,655 participants from the 45 and Up Study (New South Wales, Australia), who had fully retired between the ages of 45 and 64. We examined the associations of depression and heart disease with ill-health retirement and then adjusted for the presence of common confounders. We then restricted the sample to the 1165 individuals with heart disease prior to retirement, to determine the impact of comorbid depression on IHR and analysed whether there was a differential impact by gender. Results: In the complete sample, 3836 out of 20,655 (18.6%) of the participants retired early due to ill health. Prior heart disease and depression were both independently and strongly associated with ill-health retirement. Those who retired due to ill health were also more likely to be men, less educated, report greater physical disability and were younger at retirement. Among the 1165 for whom heart disease predated any form of retirement, 40% retired due to ill health. Comorbid depression prior to ill-health retirement was strongly associated with an increased risk of this IHR in women (odds ratio = 2.85; 95% confidence interval = 1.20–6.77, p = 0.01), but not in men (interaction term, p = 0.045). Conclusions: Ill-health retirement is common in those with heart disease. Women appear to be particularly susceptible to the effects of comorbid depression. Given the policy emphasis on reducing the number of people leaving the workforce early, women with early heart disease may represent a particular group in whom interventions designed to detect and treat comorbid depression should be targeted.
Efficacy of Radiation Countermeasures Depends on Radiation Quality

The detonation of a nuclear weapon or a nuclear accident represent possible events with significant exposure to mixed neutron/γ-radiation fields. Although radiation countermeasures generally have been studied in subjects exposed to pure photons (γ or X rays), the mechanisms of injury of these low linear energy transfer (LET) radiations are different from those of high-LET radiation such as neutrons, and these differences may affect countermeasure efficacy. We compared 30-day survival in mice after varying doses of pure γ and mixed neutron/γ (mixed field) radiation (MF, Dn/Dt = 0.65), and also examined peripheral blood cells, bone marrow cell reconstitution, and cytokine expression. Mixed-field-irradiated mice displayed prolonged defects in T-cell populations compared to mice irradiated with pure γ photons. In mouse survival assays, the growth factor granulocyte colony-stimulating factor (G-CSF) was effective as a (post-irradiation) mitigator against both γ-photons and mixed-field radiation, while the thrombopoietin (TPO) mimetic ALXN4100TPO was effective only against γ irradiation. The results indicate that radiation countermeasures should be tested against radiation qualities appropriate for specific scenarios before inclusion in response plans.
Evolving Possibilistic Fuzzy Modeling for Realized Volatility Forecasting With Jumps

Equity asset volatility modeling and forecasting provide key information for risk management, portfolio construction, financial decision making, and derivative pricing. Realized volatility models outperform autoregressive conditional heteroskedasticity and stochastic volatility models in out-of-sample forecasting. Gain in forecasting performance is achieved when models comprise volatility jump components. This paper suggests evolving possibilistic fuzzy modeling to forecast realized volatility with jumps. The modeling approach is based on an extension of the possibilistic fuzzy c-means clustering and on functional fuzzy rule-based models. It employs memberships and typicalities to recursively update cluster centers. The evolving nature of the model allows adding or removing clusters using statistical distance-like criteria to update the model as dictated by input data. The possibilistic model improves robustness to noisy data and outliers, an essential requirement in financial markets volatility modeling and forecasting. Computational experiments and statistical analysis are done using value-at-risk estimates to evaluate and compare the performance of the evolving possibilistic fuzzy modeling with the heterogeneous autoregressive model, neural networks and current state-of-the-art evolving fuzzy models. The experiments use actual data from S&P 500 and Nasdaq (U.S.), FTSE (U.K.), DAX (Germany), IBEX (Spain), and Ibovespa (Brazil), major equity market indexes in global markets. The results show that the evolving possibilistic fuzzy model is highly efficient to model realized volatility with jumps in terms of forecasting accuracy.
Kinetics of Maize Leaf Elongation : III. Silver Thiosulfate Increases the Yield Threshold of Salt-Stressed Plants, but Ethylene Is Not Involved.

The involvement of ethylene in the short-term responses of maize (Zea mays L.) leaf elongation to salinity was investigated. Leaf elongation rates (LER) were monitored with linear variable differential transformers. Salinity (80 mm NaCl) rapidly inhibited LER. Pretreatment with 4 mm silver thiosulfate (STS), an inhibitor of ethylene action, decreased LER of salt-stressed plants, but not that of controls. Investigation of the growth parameters affected by the interaction of STS and salinity indicated that the yield threshold was increased and the cell wall extensibility was decreased. All other growth parameters controlling cell elongation were unaffected. Further investigation indicated that ethylene production may not be involved in this reponse because treatments with 10 mum aminoethoxyvinylglycine, an ethylene biosynthesis inhibitor, did not affect the growth of salt-stressed plants, and no increase in ethylene production was detected in salt-stressed plants compared with controls. No changes in sensitivity to ethylene were evident because LER of both control and salt-stressed plants were inhibited to the same extent with exposure to 1.2 ppm ethylene. The above evidence indicated that ethylene was not involved in the short-term LER responses of salt-stressed maize.
Signal Transduction Stress-Induced CXCR 4 Promotes Migration and Invasion of Ewing Sarcoma

Ewing sarcoma is the second most common bone cancer in pediatric patients. Although the primary cause of death in Ewing sarcoma is metastasis, the mechanism underlying tumor spread needs to be elucidated. To this end, the role of the CXCR4/SDF-1a chemokine axis as a mediator of Ewing sarcoma metastasis was investigated. CXCR4 expression status was measured in primary tumor specimens by immunohistochemical staining and in multiple cell lines by quantitative reverse transcriptase PCR and flow cytometry. Migration and invasion of CXCR4-positive Ewing sarcoma cells toward CXCL12/SDF-1a were also determined. Interestingly, while CXCR4 status was disparate among Ewing sarcoma cells, ranging from absent to high-level expression, its expression was found to be highly dynamic and responsive to changes in the microenvironment. In particular, upregulation of CXCR4 occurred in cells that were subjected to growth factor deprivation, hypoxia, and space constraints. This upregulation of CXCR4 was rapidly reversed upon removal of the offending cellular stress conditions. Functionally, CXCR4-positive cells migrated and invaded toward an SDF1a gradient and these aggressive properties were impeded by both the CXCR4 small-molecule inhibitor AMD3100, and by knockdown of CXCR4. In addition, CXCR4-dependent migration and invasion were inhibited by small-molecule inhibitors of Cdc42 and Rac1, mechanistically implicating these Rho-GTPases as downstream mediators of the CXCR4-dependent phenotype. Implications:This study reveals the highly plastic and dynamic nature ofCXCR4 expression in Ewing sarcoma and supports amodel inwhich stress-induced upregulation ofCXCR4 contributes to tumormetastasis to lung and bone marrow, which express high levels of SDF-1a. Mol Cancer Res; 12(6); 953–64. 2014 AACR.
Comparative Systems Biology Analysis of Microbial Pathogens

Author(s): Monk, Jonathan Mayock | Advisor(s): Palsson, Bernhard O | Abstract: Genome-scale models of microbial metabolism have become a commonly used tool in the systems biology toolbox. These tools can predict, based solely on an organism’s genome sequence, its metabolic capabilities and unique phenotypes in different conditions and under unique perturbations. Furthermore, an array of in-silico methods have been developed that can be applied to these models to more deeply characterize an organism, re-engineer it and even to design effective ways to interrupt and kill it. This dissertation discusses the creation and analysis of multiple genome-scale models of metabolism for different microbial pathogens. Chapter 1 describes aspects of systems biology that are used throughout this thesis. Topics include the theory and practice of metabolic network reconstruction, genome-scale modelling and flux balance analysis. Chapter 2 focuses on the reconstruction and analysis of multiple genome-scale metabolic reconstructions of diverse Escherichia coli strains. The results highlight strain-specific adaptations to nutritional environments.Chapter 3 details comparative genome-scale modelling of multiple S. aureus strains to identify strain-specific pathogenic characteristics and unique metabolic capabilities that are related to infectious capabilities.Chapter 4 engages in a comparative metabolic network analysis and modelling of four Leptospira species that provide insight into pathogenesis of Leptospirosis.Chapter 5 examines seven industrially relevant strains of E. coli using transcriptomics and genome-scale models to quantifying variation between the strains that will likely have an impact on host strain selection for metabolic engineering applications.Chapter 6 conducts an in-depth analysis of existing metabolic network reconstructions and identifies areas where they may need further development.Chapter 7 details the construction of an updated comprehensive and high-quality genome-scale reconstruction for Escherichia coli K-12 MG1655. The model is experimentally validated with gene-knockout studies. Extension to the model are provided, including an application involving production of reactive oxygen species.Chapter 8 describes the reconstruction of a metabolic network and associated three-dimensional protein structures for Staphlyococcus aureus USA300. The model is used to examine basic S. aureus biochemistry.Chapter 9 examines the current state and predicted future of systems biology applications for studying, examining and comparing microbial pathogens.
Channel Coding for Future Space Missions: New Requirements and Trends

Future space missions will put severe constraints on communication links in terms of data rates, bandwidth occupancy, complexity, and performance. The requirements imposed by the new missions and their consequences on channel code design are presented in the first part of the paper. All relevant issues, including code rates, frame lengths, modulation formats, performance metrics, complexity, and others, are discussed. In the second part of the paper, long erasure correcting codes are presented and their properties explained. These codes operate at the upper layers of the space link protocol and constitute an attractive new frontier for zero packet loss in future space communications.
Status Distinction and Legitimation of Power as Reflected in Changing Patterns of Consumption in Late Prehispanic Peru

Patterns in household consumption reflect changing strategies of control, finance, and legitimation used by the Inka empire after their conquest of the northern Wanka of Central Peru. Changes in consumption reflect differential access to goods. In pre-Inka Wanka II, the evidence of social stratification was relatively marked; in Wanka III—under Inka domination—this difference continued but narrowed significantly. The symbolic referents of prestige wares that distinguished elites from commoners changed from local styles to those conforming to Inka stylistic canons. We also recognize changing participation in activities associated with economic control and legitimation. In Wanka II, elite households yielded evidence of greater involvement in storage and feasting. In Wanka III, the overall quantities of items associated with these activities fell and the difference between elites and commoners was diminished as the state co-opted local elite prerogatives of status and power.
Extended VQM model for predicting 3D video quality considering ambient illumination context

To speed-up the proliferation of advanced 3-Dimensional (3D) technologies into the consumer market, the influence of these technologies on the perception of 3D video should be determined. Currently, this can only be achieved using either subjective assessment techniques or 2D objective quality evaluation models. Even though the subjective assessment techniques are better than the objective models from the accuracy point of view, they are time consuming and costly. Thus, 2D objective quality evaluation models correlating with Human Visual System (HVS) should be used to predict the 3D video quality perception of users in a reliable way with less effort. Video Quality Metric (VQM), which is a standardized 2D objective quality measurement model due to its well correlation with HVS, is used to predict 3D video quality perception of users reliably. However, ambient illumination context of the viewing environment, which has an effect on 3D video quality perception, is not considered in the quality assessments by VQM. Content adaptation is one of the key applications that need to use the perceived 3D quality assessments under different ambient illumination conditions at regular basis for ensuring improved video experience of users. Therefore, the standardized VQM model is extended using ambient illumination context and content related contexts (i.e., motion, structural feature, and luminance contrast) to predict 3D video quality measurement under a particular ambient illumination condition. The results prove that the extended VQM model can be efficiently utilized to predict the video quality perception of 3D video under a particular ambient illumination condition.