Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclooxygenase 2 Promotes Cell Survival by Stimulation of Dynein Light Chain Expression and Inhibition of Neuronal Nitric Oxide Synthase Activity

ABSTRACT Cyclooxygenase 2 (COX-2) inhibits nerve growth factor (NGF) withdrawal apoptosis in differentiated PC12 cells. The inhibition of apoptosis by COX-2 was concomitant with prevention of caspase 3 activation. To understand how COX-2 prevents apoptosis, we used cDNA expression arrays to determine whether COX-2 regulates differential expression of apoptosis-related genes. The expression of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase [PIN]) was significantly stimulated in PC12 cells overexpressing COX-2. The COX-2-dependent stimulation of DLC expression was, at least in part, mediated by prostaglandin E2. Overexpression of DLC also inhibited NGF withdrawal apoptosis in differentiated PC12 cells. Stimulation of DLC expression resulted in an increased association of DLC/PIN with neuronal nitric oxide synthase (nNOS), thereby reducing nNOS activity. Furthermore, nNOS expression and activity were significantly increased in differentiated PC12 cells after NGF withdrawal. This increased nNOS activity as well as increased nNOS dimer after NGF withdrawal were inhibited by COX-2 or DLC/PIN overexpression. An nNOS inhibitor or a membrane-permeable superoxide dismutase (SOD) mimetic protected differentiated PC12 cells from NGF withdrawal apoptosis. In contrast, NO donors induced apoptosis in differentiated PC12 cells and potentiated apoptosis induced by NGF withdrawal. The protective effects of COX-2 on apoptosis induced by NGF withdrawal were also overcome by NO donors. These findings suggest that COX-2 promotes cell survival by a mechanism linking increased expression of prosurvival genes coupled to inhibition of NO- and superoxide-mediated apoptosis.
Effects of faba beans with different concentrations of vicine and convicine on egg production, egg quality and red blood cells in laying hens

The faba bean (Vicia faba L.) is a potential source of proteins for poultry, mainly for laying hens whose protein requirements are lower than those of other birds such as growing broilers and turkeys. However, this feedstuff contains anti-nutritional factors, that is, vicine (V) and convicine (C) that are already known to reduce laying hen performance. The aim of the experiment reported here was to evaluate the effects of a wide range of dietary V and C concentrations in laying hens. Two trials were performed with laying hens fed diets including 20% or 25% of faba bean genotypes highly contrasting in V+C content. In Trial 1, faba beans from two tannin-containing cultivars, but with high or low V+C content were dehulled in order to eliminate the tannin effect. In addition to the contrasting levels of V+C in the two cultivars, two intermediate levels of V+C were obtained by mixing the two cultivars (70/30 and 30/70). In Trial 2, two isogenic zero-tannin faba bean genotypes with high or low V+C content were used. In both trials, a classical corn–soybean diet was also offered to control hens. Each experimental diet was given to 48 laying hens for 140 (Trial 1) or 89 (Trial 2) days. Laying performance and egg quality were measured. The redox sensitivity of red blood cells (RBCs) was assessed by measuring hemolysis and reduced glutathione (GSH) concentration in these cells. Egg weight was significantly reduced by the diets containing the highest concentrations of V+C (P<0.0001) in Trial 1 and slightly reduced (P<0.10) in Trial 2, but only weak linear relationships between egg weight and dietary V+C concentration were established. No negative effect of V+C level was observed for egg quality parameters. In contrast, certain parameters (i.e. Haugh units, yolk color) were improved by feeding low V+C diets (P<0.05). Hemolysis of RBCs was higher in hens fed high V+C diets. A decrease in GSH concentration in RBCs of hens fed the highest levels of V+C was observed. Faba bean genotypes with low concentrations of V+C can therefore be used in laying hen diets up to 25% without any detrimental effects on performance levels or egg characteristics, without any risk of hemolysis of RBCs.
Acetylcholine induces GABA release onto rod bipolar cells through heteromeric nicotinic receptors expressed in A17 amacrine cells

Acetylcholine (ACh) is a major retinal neurotransmitter that modulates visual processing through a large repertoire of cholinergic receptors expressed on different retinal cell types. ACh is released from starburst amacrine cells (SACs) under scotopic conditions, but its effects on cells of the rod pathway have not been investigated. Using whole-cell patch clamp recordings in slices of rat retina, we found that ACh application triggers GABA release onto rod bipolar (RB) cells. GABA was released from A17 amacrine cells and activated postsynaptic GABAA and GABAC receptors in RB cells. The sensitivity of ACh-induced currents to nicotinic ACh receptor (nAChR) antagonists (TMPH ~ mecamylamine > erysodine > DhβE > MLA) together with the differential potency of specific agonists to mimic ACh responses (cytisine >> RJR2403 ~ choline), suggest that A17 cells express heteromeric nAChRs containing the β4 subunit. Activation of nAChRs induced GABA release after Ca2+ accumulation in A17 cell dendrites and varicosities mediated by L-type voltage-gated calcium channels (VGCCs) and intracellular Ca2+ stores. Inhibition of acetylcholinesterase depolarized A17 cells and increased spontaneous inhibitory postsynaptic currents in RB cells, indicating that endogenous ACh enhances GABAergic inhibition of RB cells. Moreover, injection of neostigmine or cytisine reduced the b-wave of the scotopic flash electroretinogram (ERG), suggesting that cholinergic modulation of GABA release controls RB cell activity in vivo. These results describe a novel regulatory mechanism of RB cell inhibition and complement our understanding of the neuromodulatory control of retinal signal processing.
Oxygen uptake and energy expenditure for children during rock climbing activity.

The purpose of this study was to measure oxygen uptake and energy expenditure in children during rock climbing activity. 29 children (age = 10.9 ± 1.7 yr) participated in the study. A commercially available rock climbing structure with ample features for submaximal effort climbing provided continuous terrain. Participants were instructed to climb at a comfortable pace. Following an initial 5-min rest, each child climbed one sustained 5-min bout followed by 5-min sitting recovery for a total of 10 min (SUS). This was immediately followed by five 1-min climbing + 1-min recovery intervals for a second total of 10 min (INT). Expired air was analyzed continuously. Energy expenditure (EE) was determined via the Weir method for 10-s intervals throughout the full protocol. The total energy expenditure in kilocalories during the 10-min SUS period was 34.3 ± 11.3 kcal. Energy expenditure during the 10-min INT period averaged 39.3 ± 13.1 kcal and was significantly higher than during SUS (p < .05). The mean total EE for SUS + INT was 73.7 ± 24.2 kcal. EE was correlated with body mass; r = . 86. The rock climbing tasks employed in this study produced EE levels similar to what have been reported in children for stair climbing, sports/games activities, and easy jogging.
Accepted for Publication in Ieee Transacations on Computer-aided Design of Integrated Circuits and Systems, 2017 Falcon: Feature Driven Selective Classification for Energy-efficient Image Recognition

—Machine-learning algorithms have shown outstanding image recognition/classification performance for computer vision applications. However, the compute and energy requirement for implementing such classifier models for large-scale problems is quite high. In this paper, we propose Feature Driven Selective Classification (FALCON) inspired by the biological visual attention mechanism in the brain to optimize the energy-efficiency of machine-learning classifiers. We use the consensus in the characteristic features (color/texture) across images in a dataset to decompose the original classification problem and construct a tree of classifiers (nodes) with a generic-to-specific transition in the classification hierarchy. The initial nodes of the tree separate the instances based on feature information and selectively enable the latter nodes to perform object specific classification. The proposed methodology allows selective activation of only those branches and nodes of the classification tree that are relevant to the input while keeping the remaining nodes idle. Additionally, we propose a programmable and scalable Neuromorphic Engine (NeuE) that utilizes arrays of specialized neural computational elements to execute the FALCON based classifier models for diverse datasets. The structure of FALCON facilitates the reuse of nodes while scaling up from small classification problems to larger ones thus allowing us to construct classifier implementations that are significantly more efficient. We evaluate our approach for a 12-object classification task on the Caltech101 dataset and 10-object task on CIFAR-10 dataset by constructing FALCON models on the NeuE platform in 45nm technology. Our results demonstrate up to 3.66x improvement in energy-efficiency for no loss in output quality, and even higher improvements of up to 5.91x with 3.9% accuracy loss compared to an optimised baseline network. In addition, FALCON shows an improvement in training time of up to 1.96x as compared to the traditional classification approach.
Evaluation of a stabilizer for biped walk with toe support phase

We discuss a feedback controller to stabilize biped walking which has toe support phase mimicking human gait. Using a reference walking pattern proposed in our previous work [11], our stabilizer can realize reliable walking. To evaluate the quality of stabilization, we propose two indicators, the maximum floor reaction force and the root mean square of the CoM tracking error. From our walking experiments, these indicators suggest us two policies of control parameter tuning, (1) not to control ZMP at toe support, and (2) not to use the ZMP phase-lead compensation for sagittal motion. These findings were validated by simulations of linear inverted pendulum model. It is shown that the observed behavior of the controller is caused by large velocity dissipation at support exchange.
Involvement of Sodium Nitroprusside (SNP) in the Mechanism That Delays Stem Bending of Different Gerbera Cultivars

Longevity of cut flowers of many gerbera cultivars (Gerbera jamesonii) is typically short because of stem bending; hence, stem bending that occurs during the early vase life period is a major problem in gerbera. Here, we investigated the effects of sodium nitroprusside (SNP) on the delay of stem bending in the gerbera cultivars, Alliance, Rosalin, and Bintang, by examining relative fresh weight, bacterial density in the vase solution, transcriptional analysis of a lignin biosynthesis gene, antioxidant activity, and xylem blockage. All three gerbera cultivars responded to SNP by delaying stem bending, compared to the controls; however, the responses were dose- and cultivar-dependent. Among the treatments, SNP at 20 mg L-1 was the best to delay stem bending in Alliance, while dosages of 10 and 5 mg L-1 were the best for Rosalin and Bintang, respectively. However, stem bending in Alliance and Rosalin was faster than in Bintang, indicating a discrepancy influenced by genotype. According to our analysis of the role of SNP in the delay of stem bending, the results revealed that SNP treatment inhibited bacterial growth and xylem blockage, enhanced expression levels of a lignin biosynthesis gene, and maintained antioxidant activities. Therefore, it is suggested that the cause of stem bending is associated with the above-mentioned parameters and SNP is involved in the mechanism that delays stem bending in the different gerbera cultivars.
Free boundary problems in shock reflection/diffraction and related transonic flow problems

Shock waves are steep wavefronts that are fundamental in nature, especially in high-speed fluid flows. When a shock hits an obstacle, or a flying body meets a shock, shock reflection/diffraction phenomena occur. In this paper, we show how several long-standing shock reflection/diffraction problems can be formulated as free boundary problems, discuss some recent progress in developing mathematical ideas, approaches and techniques for solving these problems, and present some further open problems in this direction. In particular, these shock problems include von Neumann's problem for shock reflection–diffraction by two-dimensional wedges with concave corner, Lighthill's problem for shock diffraction by two-dimensional wedges with convex corner, and Prandtl-Meyer's problem for supersonic flow impinging onto solid wedges, which are also fundamental in the mathematical theory of multidimensional conservation laws.
Additive Anti-Tumor Effects of Lovastatin and Everolimus In Vitro through Simultaneous Inhibition of Signaling Pathways

Background The mTORC1-inhibitor everolimus shows limited efficacy in treating patients with gastro-entero-pancreatic or pulmonary neuroendocrine tumors (NETs), and poor outcome in patients with malignant pheochromocytoma or hepatic carcinoma. We speculated that any effect may be enhanced by antogonising other signaling pathways. Methods Therefore, we tested the effect of lovastatin—known to inhibit both ERK and AKT signaling—and everolimus, separately and in combination, on cell viability and signaling pathways in human midgut (GOT), pancreatic (BON1), and pulmonary (H727) NET, hepatocellular carcinoma (HepG2, Huh7), and mouse pheochromocytoma (MPC, MTT) cell lines. Results Lovastatin and everolimus separately significantly reduced cell viability in H727, HepG2, Huh7, MPC and MTT cells at clinically relevant doses (P ≤ 0.05). However, high doses of lovastatin were necessary to affect GOT or BON1 cell viability. Clinically relevant doses of both drugs showed additive anti-tumor effects in H727, HepG2, Huh7, MPC and MTT cells (P ≤ 0.05), but not in BON1 or GOT cells. In all cell lines investigated, lovastatin inhibited EGFR and AKT signaling. Subsequently, combination treatment more strongly inhibited EGFR and AKT signaling than everolimus alone, or at least attenuated everolimus-induced EGFR or AKT activation. Vice versa, everolimus constantly decreased pp70S6K and combination treatment more strongly decreased pp70S6K than lovastatin alone, or attenuated lovastatin-induced p70S6K activation: in BON1 cells lovastatin-induced EGFR inhibition was least pronounced, possibly explaining the low efficacy and consequent absent additive effect. Conclusion In summary, clinically relevant doses of lovastatin and everolimus were effective separately and showed additive effects in 5 out of 7 cell lines. Our findings emphasize the importance of targeting several interacting signaling pathways simultaneously when attempting to attenuate tumor growth. However, the variable reactions of the different cell lines highlight the necessity to understand the unique molecular aberrations in any tumor. Nevertheless, this combination seems worthy of being tested in vivo.
Post-Transcriptional Up-Regulation of PDGF-C by HuR in Advanced and Stressed Breast Cancer

Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.
Deprenyl is metabolized to methamphetamine and amphetamine in man.

CHOUINARD, G. & JONES, B.D. (1978). Schizophrenia as dopamine-deficiency disease. Lancet, ii, 99-100. CROW, T.J., DEAKIN, J.F. W. , JOHNSTONE, E.C. & LONGDEN, A. (1976). Dopamine and schizophrenia. Lancet, ii, 563-566. DEBONO, A.G. , MARSDEN, C.D. , ASSELMAN, P. & PARKES, J.D. (1976). Bromocriptine and dopamine receptor stimulation. Br. J. clin. Pharnac. , 3, 977-982. JOHNSTONE, E.C. , CROW, T.J., FRITH, C.D. , CARNEY, M.W. P. & PRICE, J.S. (1978). Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848-851. KAPIT, R.M. (1977). Schizophrenia and tardive dyskinesia: is schizophrenia also a 'denervation hypersensitivity'? Medical Hypotheses, 3, 207-2 10. OWEN, F. , CROW, T.J., POULTER, M. , CROSS, A.J., LONGDEN, A. & RILEY, G.J. (1978). Increased dopamine-receptor sensitivity in schizophrenia. Lancet, ii, 223-225. PEARCE, I. & PEARCE, J.M.S. (1978). Bromocriptine in Parkinsonism. Br. med. J., 1, 1402-1404. SHAW, K.M. , LEES, AJ. & STERN, G.M. (1978). Bromocriptine in Parkinson's disease. Lancet, i, 1255. WING, J.K. (1961). A simple and reliable subclassification of chronic schizophrenia. J. mental Sci., 107, 862-875.
Magnetic interconnection of Saturn's polar regions: comparison of modelling results with Hubble Space Telescope UV auroral images

Abstract. We consider the magnetic interconnection of Saturn's northern and southern polar regions controlled by the interplanetary magnetic field (IMF), studying in particular the more complex and interesting case of southward IMF, when the Kronian magnetospheric magnetic field structure is the most twisted. The simpler case of northward IMF is also discussed. Knowledge of the magnetospheric magnetic field structure is very significant, for example, for investigation of the electric fields and field-aligned currents in Saturn's environment, particularly those which cause the auroral emissions. Here we modify the paraboloid magnetospheric magnetic field model employed in previous related studies by including higher multipole terms in Saturn's internal magnetic field, required for more detailed considerations of inter-hemispheric conjugacy, together with inclusion of a spheroidal boundary at the ionospheric level. The model is employed to map Southern Hemisphere auroral regions observed by the Hubble Space Telescope (HST) in 2008 under known IMF conditions to both the equatorial plane and the northern ionosphere. It is shown that the brightest auroral features map typically to the equatorial region between the central ring current and the outer magnetosphere, and that auroral features should be largely symmetric between the two hemispheres, except for a small poleward displacement and latitudinal narrowing in the Northern Hemisphere compared with the Southern Hemisphere due to the quadrupole field asymmetry. The latter features are in agreement with the conjugate auroras observed under near-equinoctial conditions in early 2009, when IMF data are not available.
Epidural anesthesia for pilonidal sinus surgery: ropivacaine versus levobupivacaine

Background Epidural anesthesia is one of the best options for lower abdominal and lower limb surgery. However, there have been insufficient reports regarding the use of epidural anesthesia for pilonidal sinus surgery. The present study was performed to compare the clinical profiles of epidural block performed with 0.75% levobupivacaine and 0.75% ropivacaine in this procedure. Methods Thirty patients undergoing pilonidal sinus surgery were randomly allocated into two groups: one group received levobupivacaine and the other received ropivacaine at 0.75% in a volume of 10 ml. Arterial blood pressure, heart rate, oxygen saturation, the onset time of analgesia and duration of block, highest sensory block level, perioperative and postoperative side effects, and patients' and surgeons' satisfaction were recorded. Results Hemodynamic stability was maintained in both groups throughout surgery. The onset time of analgesia (the time from epidural injection of local anesthetic to reach L2 sensorial block) was 6.26 ± 3.49 min in the levobupivacaine group and 4.06 ± 1.75 min in the ropivacaine group (P = 0.116). The duration of sensorial block (time for regression of sensory block to L2) was 297.73 ± 70.94 min in group L and 332.40 ± 102.22 min in group R (P = 0.110). Motor block was not seen in any of the patients in the study groups. Patients' and surgeons' satisfaction with the anesthetic technique were mostly excellent in both groups. Conclusions In patients undergoing pilonidal sinus surgery, both levobupivacaine and ropivacaine produce rapid and excellent epidural block without leading to motor block or significant side effects. Although not statistically significant, the onset time of anesthesia was shorter and the duration of effect was longer with ropivacaine than with levobupivacaine in this study.
FAME 2: Reshaping the approach to patients with stable coronary artery disease

Contrary to its central role in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) in stable ischemic heart disease (SIHD) remains largely restricted to patients in whom medical treatment fails to control symptoms, or those with a large area of myocardium at risk and/or high risk findings on non-invasive testing.1,2 These recommendations are based on a number of studies – the largest of which is COURAGE – that failed to show any reduction in mortality or myocardial infarction (MI) with PCI compared to optimal medical therapy (OMT) in this group of patients.3 A possible limitation in these studies was relying on visual assessment of angiographic stenoses (which is now well-known to be imprecise) to determine lesions responsible for myocardial ischemia. Non-invasive stress testing – including imaging – may also be inaccurate in patients with multivessel coronary artery disease.4,5 These limitations have inadvertently led to the inclusion of patients with non-ischemic lesions in these studies, which may have diluted any potential benefit with PCI. Given the superiority of fractional flow reserve (FFR) in identifying ischemic lesions compared to angiography, Fractional flow reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) investigators hypothesized that when guided by FFR, PCI plus medical therapy would be superior to medical therapy alone in patients with SIHD.