Miracle-dz/UniFAR-FTUs huggingface dataset:
Computing the Set of all the Distant Horizons of a Terrain

We study the problem of computing the set of all distant horizons of a terrain, represented as either: (1) the set of all edges that appear on the distant horizon from at least one viewing direction; (2) for every edge e, the set of direction intervals for which e appears on the distant horizon; or (3) a search structure to query for the edges on the distant horizon, or the precise distant horizon, from a fixed viewing direction. We describe an algorithm that solves the first and second forms of the problem in O(n2+∊) time for any constant ∊ > 0 where n is the number of edges of the terrain. This algorithm can be extended to compute a search structure for (3) in O(n2+∊) time. The search structure can return the s edges on the distant horizon in O(log n + s) time. We show solving problem (1) is 3SUM hard. Furthermore, we construct a terrain with a single local maximum in which Θ(n) edges each have Θ(n) direction intervals, showing that our solution to (2) cannot be significantly improved, in the worst case, even for such restricted terrains. This takes advantage of a novel construction in which the convex hull of a set of n linearly moving points, whose trajectories do not intersect, changes Ω(n2) times.
Heart rate, blood lactate concentration, and time–motion analysis of female basketball players during competition

Abstract The aim of this study was to examine the physiological demands and movement patterns of female basketball players after changes in the rules of the game. Nine varsity players were studied during nine official games. Each game was videotaped to identify the frequencies of the main movements performed, heart rate was recorded continuously, and blood samples were collected to determine blood lactate concentration when the competition rules allowed. The main results showed that the players performed on average 652 ± 128 movements per game, which corresponded to a change in activity every 2.82 s. Mean heart rate was 165 ± 9 beats · min−1 (89.1% of maximum heart rate) for total time and 170 ± 8 beats · min−1 (92.5% of maximum) for live time. Mean blood lactate concentration was 5.2 ± 2.7 mmol · l−1 (55.9% of maximum blood lactate concentration). In addition, heart rates were significantly higher in the first half than the second half of games. These results indicate: (1) a greater physiological load compared with previous studies on female players tested before the rules modification (Beam & Merrill, 1994; McArdle et al., 1971) and (2) lower movement frequencies compared with male players competing under modern rules (Ben Abdelkrim et al., 2007). These observations must be taken into account by coaches and conditioning specialists working with female players.
A Chinese Chan-based lifestyle intervention improves memory of older adults

This study aims to explore the potential benefits of a Chinese Chan-based lifestyle intervention on enhancing memory in older people with lower memory function. Forty-four aged 60–83 adults with various level of memory ability participated in the study. Their memories (including verbal and visual components) were assessed before and after 3 months intervention. The intervention consisted of 12 sessions, with one 90 min session per week. The intervention involved components of adopting a special vegetarian diet, practicing a type of mind–body exercises, and learning self-realization. Elderly with lower memory function at the baseline (i.e., their performance on standardized memory tests was within 25th percentile) showed a significant memory improvement after the intervention. Their verbal and visual memory performance has showed 50 and 49% enhancement, respectively. In addition, their improvement can be considered as a reliable and clinically significant change as reflected by their significant pre–post differences and reliable change indices. Such robust treatment effect was found to be specific to memory functions, but less influencing on the other cognitive functions. These preliminary encouraging results have shed some light on the potential applicability of the Chinese Chan-based lifestyle intervention as a method for enhancing memory in the elderly population.
Drugs or diet? – Developing novel therapeutic strategies targeting the free fatty acid family of GPCRs

Free fatty acids (FFAs) are metabolic intermediates that may be obtained through the diet, synthesized endogenously, or produced via fermentation of carbohydrates by gut microbiota. In addition to serving as an important source of energy, FFAs are known to produce a variety of both beneficial and detrimental effects on metabolic and inflammatory processes. While historically, FFAs were believed to produce these effects only through intracellular targets such as peroxisome proliferator‐activated receptors, it has now become clear that FFAs are also agonists for several GPCRs, including a family of four receptors now termed FFA1‐4. Increasing evidence suggests that FFA1‐4 mediate many of the beneficial properties of FFAs and not surprisingly, this has generated significant interest in the potential of these receptors as therapeutic targets for the treatment of a variety of metabolic and inflammatory disorders. In addition to the traditional strategy of developing small‐molecule therapeutics targeting these receptors, there has also been some consideration given to alternate therapeutic approaches, specifically by manipulating endogenous FFA concentrations through alteration of either dietary intake, or production by gut microbiota. In this review, the current state of knowledge for FFA1‐4 will be discussed, together with their potential as therapeutic targets in the treatment of metabolic and inflammatory disorders. In particular, the evidence in support of small molecule versus dietary and microbiota‐based therapeutic approaches will be considered to provide insight into the development of novel multifaceted strategies targeting the FFA receptors for the treatment of metabolic and inflammatory disorders.
Detection of Ventilator Autotriggering by an Esophageal Catheter Used to Monitor the Neural Input and Diaphragm Excitation

Patient-ventilator synchrony has been the focus of attention in the field of mechanical ventilation for quite some time now. Toward that end, the modern ventilators are equipped with very sensitive pneumatic triggering mechanisms, which allow for minimal wasting of patient effort. The increasingly sensitive pneumatic triggers have the potential to cause autotriggering, where stimuli other than neural signals (eg, cardiac oscillations) can trigger the mechanical breath. Although autotriggering has been well documented in brain-dead patients, its existence is difficult to prove in patients who have the ability to trigger breath through neural diaphragmatic activity. The only way to be sure that the triggered breath is indeed from the neural diaphragmatic activity rather than a spurious change in pressure or flow is to monitor neural signals during triggered mechanical breaths. Autotriggering can have deleterious effects including diaphragmatic atrophy, increased duration on the mechanical ventilator, and increased stay in the intensive care unit. Esophageal catheters, with the ability to measure phrenic nerve and diaphragmatic activity, allow for the detection of the extent of autotriggering. This article demonstrates the hitherto unknown but potentially common occurrence of autotriggering through nonneural stimuli and their amelioration by making the pneumatic autotriggering less sensitive. The full extent of the phenomenon and its deleterious effects remain to be explored in larger patient populations.
Discovery of Ixabepilone

The discovery of the antineoplastic agent paclitaxel and its unique activity as a microtubule-stabilizing agent resulted in dramatic improvements in the treatment of breast, ovarian, and non-small cell lung cancers. Despite the potent antitumor activity of taxanes such as paclitaxel, efficacy of these agents has been limited by development of taxane-resistant tumors in patients. This review describes, with some historical context, our successful efforts to discover a next-generation microtubule-stabilizing agent for the treatment of cancer. In collaboration with the Gesellschaft für Biotechnologische Forschung, we evaluated the epothilones, originally isolated from the myxobacterium Sorangium cellulosum, as potential anticancer agents. Experiments performed at Bristol-Myers Squibb confirmed the ability of these agents to induce tubulin polymerization, cell cycle arrest, and apoptosis. Epothilones A and B showed potent cytotoxic activity toward paclitaxel-sensitive and paclitaxel-resistant cells expressing P-glycoprotein or mutant tubulin. Because the parent epothilones were subject to inactivation via esterase cleavage, we used semisynthetic approaches to prepare analogues without this liability. BMS-247550 (ixabepilone), the lactam analogue of epothilone B, showed increased metabolic stability, potent tubulin polymerization activity, and retained activity against paclitaxel-resistant lines. Based on its shown efficacy in clinical trials, ixabepilone was approved by the Food and Drug Administration in 2007 for treatment of drug-resistant/refractory metastatic or locally advanced breast cancer. [Mol Cancer Ther 2009;8(2):275–81]
Zds1 regulates PP2ACdc55 activity and Cdc14 activation during mitotic exit through its Zds_C motif

Summary At anaphase onset, highly active mitotic cyclin-dependent kinase (Cdk) is inactivated to promote exit from mitosis and completion of cytokinesis. The budding yeast Cdc14p phosphatase is a key mitotic regulator that counteracts cyclin-dependent kinase (Cdk) activity during mitotic exit. Separase, together with Zds1p, promotes the downregulation of the protein phosphatase 2A in conjunction with its Cdc55p regulatory subunit (PP2ACdc55) in early anaphase, enabling accumulation of phosphorylated forms of Net1p and release of Cdc14p from the nucleolus. Here we show that the C-terminal domain of Zds1p, called the Zds_C motif, is required for Zds1-induced release of Cdc14p, and the N-terminal domain of the protein might be involved in regulating this activity. More interestingly, Zds1p physically interacts with Cdc55p, and regulates its localization through the Zds_C motif. Nevertheless, expression of the Zds_C motif at endogenous levels cannot induce timely release of Cdc14p from the nucleolus, despite the proper (nucleolar) localization of Cdc55p. Our results suggest that the activity of PP2ACdc55 cannot be modulated solely through regulation of its localization, and that an additional regulatory step is probably required. These results suggest that Zds1p recruits PP2ACdc55 to the nucleolus and induces its inactivation by an unknown mechanism.
Death in Asthmatics

In recent years it has become accepted that asthma is not the benign disorder which leads to discomfort but never to death that it was thought to be 30 years ago. Following the pioneer paper of Huber and Koessler (1922), a number of workers have published series of fatal cases and commented on the pathological findings. This literature has been reviewed by Unger (1952), by Earle (1953), and by Robertson and Sinclair (1954) and more recent reports are those of Alexander (1958) and Williams and Leopold (1958). It is obvious from a study of this literature that the term asthma is often used to include cases of varying aetiology and to describe a syndrome rather than a disease. Until a clearer notion of the pathogenesis of asthma is obtained some confusion of terminology will inevitably continue. Meanwhile it is firmly established that asthma can be lethal, though the role of allergy, of infection, and of several other factors is not yet fully elucidated. In this paper we hope to show that the comparison of clinical and pathological features of fatal cases of asthma can still provide useful information.
Mitochondrial depolarization following hydrogen sulfide exposure in erythrocytes from a sulfide-tolerant marine invertebrate

SUMMARY Sulfide-tolerant marine invertebrates employ a variety of mechanisms to detoxify sulfide once it has entered their bodies, but their integumentary, respiratory epithelium and circulatory cells may still be exposed to toxic sulfide concentrations. To investigate whether sulfide exposure is toxic to mitochondria of a sulfide-tolerant invertebrate, we used the fluorescent dyes JC-1 and TMRM to determine the effect of sulfide exposure on mitochondrial depolarization in erythrocytes from the annelid Glycera dibranchiata. In erythrocytes exposed to 0.11-1.9 mmol l-1 sulfide for 1 h, the dyes showed fluorescence changes consistent with sulfide-induced mitochondrial depolarization. At the highest sulfide concentration, the extent of depolarization was equivalent to that caused by the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). Even when induced by as little as 0.3 mmol l-1 sulfide, the depolarization was not reversible over a subsequent 5 h recovery period. The mechanism of toxicity was likely not via inhibition of cytochrome c oxidase (COX), since other COX inhibitors and other mitochondrial electron transport chain inhibitors did not produce similar effects. Furthermore, pharmacological inhibition of the mitochondrial permeability transition pore failed to prevent sulfide-induced depolarization. Finally, increased oxidation of the free radical indicators H2DCFDA and MitoSOX™ in erythrocytes exposed to sulfide suggests that sulfide oxidation increased oxidative stress and superoxide production, respectively. Together, these results indicate that sulfide exposure causes mitochondrial depolarization in cells of a sulfide-tolerant annelid, and that this effect, which differs from the actions of other COX inhibitors, may be via increased free radical damage.
Selective oxidation of glycerol under acidic conditions using gold catalysts.

H-mordenite-supported PtAu nanoparticles are highly active and selective in the oxidation of glycerol under acidic conditions, which allows the direct preparation of free acids (see picture). The high selectivity for C{sub 3} compounds results from the negligible formation of H{sub 2}O{sub 2}, in contrast to PtAu nanoparticles supported on activated carbon.
A Benzothiophene Inhibitor of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Inhibits Tumor Necrosis Factor α Production and Has Oral Anti-Inflammatory Efficacy in Acute and Chronic Models of Inflammation

Activation of the p38 kinase pathway in immune cells leads to the transcriptional and translational regulation of proinflammatory cytokines. Mitogen-activated protein kinase-activated protein kinase 2 (MK2), a direct downstream substrate of p38 kinase, regulates lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) production through modulating the stability and translation of these mRNAs. Developing small-molecule inhibitors of MK2 may yield anti-inflammatory efficacy with a different safety profile relative to p38 kinase inhibitors. This article describes the pharmacologic properties of a benzothiophene MK2 inhibitor, PF-3644022 [(10R)-10-methyl-3-(6-methylpyridin-3-yl)-9,10,11,12-tetrahydro-8H-[1,4]diazepino[5′,6′:4,5]thieno[3,2-f]quinolin-8-one]. PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits MK2 activity (Ki = 3 nM) with good selectivity when profiled against 200 human kinases. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity (IC50 = 160 nM). PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood with IC50 values of 1.6 and 10.3 μM, respectively. Inhibition of TNFα in U937 cells and blood correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of MK2 activity. PF-3644022 displays good pharmacokinetic parameters in rats and is orally efficacious in both the rat acute LPS-induced TNFα model and the chronic streptococcal cell wall-induced arthritis model. Dose-dependent inhibition of TNFα production in the acute model and inhibition of paw swelling in the chronic model is observed with ED50 values of 6.9 and 20 mg/kg, respectively. PF-3644022 efficacy in the chronic inflammation model is strongly correlated with maintaining a Cmin higher than the EC50 measured in the rat LPS-induced TNFα model.
Optimal Parameter Selection in Support Vector Machines 1

The purpose of the paper is to apply a nonlinear programming algorithm to compute kernel and related parameters of a support vector machine (SVM) by a two-level approach. Available training data are split into two groups, one set for formulating a quadratic SVM with L2-soft margin and another one for minimizing the generalization error, where the optimal SVM variables are inserted. Subsequently, the SVM is again solved, but now for the entire set of training data, and the total generalization error is evaluated for a separate set of test data. Derivatives of the functions by which the optimization problem is defined, are evaluated in an analytical way, where an existing Cholesky decomposition needed for solving the quadratic SVM, is exploited. The approach is implemented and tested on a couple of standard data sets with up to 4,800 patterns. The results show a significant reduction of the generalization error, an increase of the margin, and a reduction of the number of support vectors in all cases where the data sets are sufficiently large. By a second set of test runs, kernel parameters are assigned to individual features. Redundant attributes are identified and suitable relative weighting factors are computed.
Similar serotonin‐2A receptor binding in rats with different coping styles or levels of aggression

Individual differences in coping style emerge as a function of underlying variability in the activation of a mesocorticolimbic brain circuitry. Particularly serotonin seems to play an important role. For this reason, we assessed serotonin‐2A receptor (5‐HT2AR) binding in the brain of rats with different coping styles. We compared proactive and reactive males of two rat strains, Wild‐type Groningen (WTG) and Roman high‐ and low avoidance (RHA, RLA). 5‐HT2AR binding in (pre)frontal cortex (FC) and hippocampus was investigated using a radiolabeled antagonist ([3H]MDL‐100907) and agonist ([3H]Cimbi‐36) in binding assays. No differences in 5‐HT2AR binding were observed in male animals with different coping styles. [3H]MDL‐100907 displayed a higher specific‐to‐nonspecific binding ratio than [3H]Cimbi‐36. Our findings suggest that in these particular rat strains, 5‐HT2AR binding is not an important molecular marker for coping style. Because neither an antagonist nor an agonist tracer showed any binding differences, it is unlikely that the affinity state of the 5‐HT2AR is co‐varying with levels of aggression or active avoidance in WTG, RHA and RLA. Synapse, 69:226–232, 2015. © 2015 Wiley Periodicals, Inc.
Multivariate Multi-Scale Permutation Entropy for Complexity Analysis of Alzheimer's Disease EEG

Abstract: An original multivariate multi-scale methodology for assessing the complexity of physiological signals is proposed. The technique is able to incorporate the simultaneous analysis of multi-channel data as a unique block within a multi-scale framework. The basic complexity measure is done by using Permutation Entropy, a methodology for time series processing based on ordinal analysis. Permutation Entropy is conceptually simple, structurally robust to noise and artifacts, computationally very fast, which is relevant for designing portable diagnostics. Since time series derived from biological systems show structures on multiple spatial-temporal scales, the proposed technique can be useful for other types of biomedical signal analysis. In this work, the possibility of distinguish among the brain states related to Alzheimer’s disease patients and Mild Cognitive Impaired subjects from normal healthy elderly is checked on a real, although quite limited, experimental database. Keywords:
Urban Built-up Areas in Transitional Economies of Southeast Asia: Spatial Extent and Dynamics

Urban built-up area, one of the most important measures of an urban landscape, is an essential variable for understanding ecological and socioeconomic processes in urban systems. With an interest in urban development in transitional economies in Southeast Asia, we recognized a lack of high-to-medium resolution (<60 m) built-up information for countries in the region, including Vietnam, Laos, Cambodia and Myanmar. In this study, we combined multiple remote sensing data, including Landsat, DMSP/OLS night time light, MODIS NDVI data and other ancillary spatial data, to develop a 30-m resolution urban built-up map of 2010 for the above four countries. Following the trend analysis of the DMSP/OLS time series and the 2010 urban built-up extent, we also quantified the spatiotemporal dynamics of urban built-up areas from 1992 to 2010. Among the four countries, Vietnam had the highest proportion of urban built-up area (0.91%), followed by Myanmar (0.15%), Cambodia (0.12%) and Laos (0.09%). Vietnam was also the fastest in new built-up development (increased ~8.8-times during the 18-year study period), followed by Laos, Cambodia and Myanmar, which increased at 6.0-, 3.6- and 0.24-times, respectively.
Circular dichroism and conformational polymorphism of DNA

Here we review studies that provided important information about conformational properties of DNA using circular dichroic (CD) spectroscopy. The conformational properties include the B-family of structures, A-form, Z-form, guanine quadruplexes, cytosine quadruplexes, triplexes and other less characterized structures. CD spectroscopy is extremely sensitive and relatively inexpensive. This fast and simple method can be used at low- as well as high-DNA concentrations and with short- as well as long-DNA molecules. The samples can easily be titrated with various agents to cause conformational isomerizations of DNA. The course of detected CD spectral changes makes possible to distinguish between gradual changes within a single DNA conformation and cooperative isomerizations between discrete structural states. It enables measuring kinetics of the appearance of particular conformers and determination of their thermodynamic parameters. In careful hands, CD spectroscopy is a valuable tool for mapping conformational properties of particular DNA molecules. Due to its numerous advantages, CD spectroscopy significantly participated in all basic conformational findings on DNA.
Personal Sexual History and Punitive Judgements for Rape

Although there have been numerous studies implicating extralegal factors as influencing the assessment of the seriousness of rape, few have considered the unique life experiences of the individual who makes such judgements. One exception, the Zillman and Bryant study, demonstrated that experimental subjects, after massive exposure to pornography, gave significantly shorter sentences to a rapist than did the controls. It is hypothesized that, if exposure to explicit sexual activity could function to desensitize one to the seriousness of rape, then an individual's sexual history could also function to alter perceptions of a rape event. On a sample of 350 university students, we tested the hypothesis that individuals with restricted sexual histories will be prone to view rape as a more serious offense than those with more extensive histories. A statistical analysis employing analysis of variance provided strong support for this hypothesis.