Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is dependent on a PKCzeta-ROS pathway.

BACKGROUND & AIMS Intestinal myofibroblasts (IMFs) express cyclooxygenase 2 (COX-2) early on in polyp progression and respond to pro-inflammatory cytokines. Interleukin (IL)-1alpha induces COX-2 expression in IMF via mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and nuclear factor kappa B (NF-kappaB)-dependent pathways. Because NF-kappaB activity can be mediated by PKC activation and reactive oxygen species (ROS) generation, we examined the relationship of these pathways to IL-1alpha-induced COX-2 expression. METHODS The effects of specific PKC inhibitors and antioxidants on PKC activation, ROS generation, and COX-2 expression were studied. RESULTS Immunoprecipitation/kinase (IPK) analysis showed that IL-1alpha increased PKC alpha, delta, and zeta activity 4.5-, 3.1-, and 2.6-fold, respectively, within 5 minutes. Single-cell fluorescence microscopy of 2',7'-dichlorofluorescin diacetate (DCF)-loaded cells showed that IL-1alpha increased ROS levels 2-fold within 15 minutes and this increase was inhibited by 10 micromol/L bisindolylymaleimide I (BIS), a pan-specific PKC inhibitor that also inhibits COX-2 expression. Chelerythrine chloride (CC) (0.5 micromol/L) inhibited classic and novel PKC activity, but not PKCzeta, and enhanced IL-1alpha-mediated ROS generation 4.0-fold and COX-2 expression 1.8-fold. The use of a PKCzeta pseudosubstrate prevented IL-1 from increasing ROS greater than control levels and abolished IL-1alpha-induced COX-2 expression. Small inhibitory RNA (siRNA) for PKCzeta confirmed its role in COX-2 expression. Antioxidants inhibited ROS generation and diminished IL-1alpha-induced COX-2 expression by 80%, without affecting PKC activation. Neither the PKC inhibitors nor the antioxidants prevented NF-kappaB-mediated transcription as determined by reporter gene analysis. CONCLUSIONS PKCzeta and threshold ROS generation are critical for IL-1alpha-induced COX-2 expression and act concomitantly with NF-kappaB translocation in IMF.
The Afghan Air War

Abstract : The Sept. 11, 2001 terror attacks in New York City and Washington, D.C., changed forever the way Americans viewed national security. For the US Air Force and its partners in joint airpower the attacks and resulting Global War on Terrorism erased distinctions between fighting over there and the defense of the United States. American strategy will be affected for decades to come. The large-scale US response to an act of terrorism was a first for the American military. Operation Enduring Freedom, the US overseas response, was in its most intense phase in the period October 2001 through January 2002, but it was not a massive air war. The sortie count from its start on Oct. 7 through the final takeover of Afghan cities was half that of Operation Allied Force in 1999 and nowhere near the effort of the Gulf War in 1991. Air Force pilots flew some of the longest missions in history, but the success of the campaign was never seriously in question. What made Enduring Freedom unique was that, in a war unlike any other, joint airpower was able to respond on command in a harsh and politically complex environment. Airpower set the conditions for the coalition campaign and achieved success from the first night onward. Airmen took it all in stride. They conducted a campaign that, initially, filled the pundits with doubts, but they made it look routine, adapting to tactical constraints and bringing precise firepower to bear wherever needed, despite the obstacles. The overarching US Global War on Terrorism does not fit neatly into the cause-and-effect calculations of international politics. Military force mingles with diplomacy, international financial sanctions, cyber-defense, law enforcement, and many other forms of response. It is in part the by-product of several regional security policies, from the effort to contain Iraq to the US relationship with Israel. It is directly a product of the emergence of a non-national group-al Qaeda-ideologically bent on destruction.
Velocity and disturbance observer for non-model based load and friction compensation

In this paper, a scheme for the simultaneous estimation of the external forces acting on a rigid body together with its velocity is presented. This estimation scheme is based only on the knowledge of the position information and it allows to compensate undesired effects acting on the rigid body, like friction or external unknown loads, without requiring any knowledge of these spurious effects. This goal is achieved by means of two interacting observers, one for the observation of the generalized momenta and another for velocity observation. This compensation scheme can be also used to give to the system the desired dynamics, therefore avoiding the problem of parameter uncertainties. The effectiveness of the proposed scheme is proved both in simulation and experimentally, with a laboratory setup composed by a linear electric drive.
A Novel Positron Emission Tomography Imaging Protocol Identifies Seizure-Induced Regional Overactivity of P-Glycoprotein at the Blood–Brain Barrier

Approximately one-third of epilepsy patients are pharmacoresistant. Overexpression of P-glycoprotein and other multidrug transporters at the blood–brain barrier is thought to play an important role in drug-refractory epilepsy. Thus, quantification of regionally different P-glycoprotein activity in the brain in vivo is essential to identify P-glycoprotein overactivity as the relevant mechanism for drug resistance in an individual patient. Using the radiolabeled P-glycoprotein substrate (R)-[11C]verapamil and different doses of coadministered tariquidar, which is an inhibitor of P-glycoprotein, we evaluated whether small-animal positron emission tomography can quantify regional changes in transporter function in the rat brain at baseline and 48 h after a pilocarpine-induced status epilepticus. P-glycoprotein expression was additionally quantified by immunohistochemistry. To reveal putative seizure-induced changes in blood–brain barrier integrity, we performed gadolinium-enhanced magnetic resonance scans on a 7.0 tesla small-animal scanner. Before P-glycoprotein modulation, brain uptake of (R)-[11C]verapamil was low in all regions investigated in control and post-status epilepticus rats. After administration of 3 mg/kg tariquidar, which inhibits P-glycoprotein only partially, we observed increased regional differentiation in brain activity uptake in post-status epilepticus versus control rats, which diminished after maximal P-glycoprotein inhibition. Regional increases in the efflux rate constant k2, but not in distribution volume VT or influx rate constant K1, correlated significantly with increases in P-glycoprotein expression measured by immunohistochemistry. This imaging protocol proves to be suitable to detect seizure-induced regional changes in P-glycoprotein activity and is readily applicable to humans, with the aim to detect relevant mechanisms of pharmacoresistance in epilepsy in vivo.
The agent-based Solow growth model with endogenous business cycles

This article describes a simulated monetary macro model with different types of interacting agents. As such, it is assigned to the field of agent-based computational economics (ACE), where agents become virtual objects in a computer simulation. The ACE model core with labor market and goods market interaction between households and firms is adopted from Lengnick (2013), whereas production technology and technological progress of firms are adopted from the neoclassical Solow (1956) model. Nominal interest rates are set in accordance with the Taylor (1993) principle, characterized by strong responses of monetary policy to deviations from inflation target. Although inflation desirably follows lagged output in a pro-cyclical manner, the dynamic system allows for long-run stability of inflation rates. Firms on aggregate level endogenously generate waves of higher and lower investment. A recurrent cyclical movement of aggregate economic activity, in particular demand, employment and inflation, is transmitted from these waves of investment activity. Cyclical patterns of boom and bust emerge with a frequency of approximately seven years just like Juglar-type cycles. Moreover, the model generates a short-run Phillips-curve relationship, long-run neutrality of monetary policy and business cycle patterns similar to the Goodwin (1967) model. Fiscal stabilization policy is shown to dampen macroeconomic fluctuations, thus allowing for a higher level of average employment. Calibration of model parameters is conducted to generate realistic orders of magnitude of important macroeconomic proportions. The newly developed model is a combination of ideas from different economic perspectives and contributes to macroeconomic model-building under the paradigm of agent-based computational economics.
Wheat starch digestion rate in broiler chickens is affected by cultivar but not by wheat crop nitrogen fertilisation

1. A study was set up to investigate the influence of wheat cultivar and wheat crop nitrogen (N) fertilisation on starch (ST) digestion rate in broiler chickens. A total of 288 broiler chickens were used in a 3 × 2 factorial design with diets based on three varieties of wheat (Apache, Caphorn and Charger), each grown at two N application rates (40 and 170 kg of N/ha). 2. Starch digestion rate was determined by measuring the remaining starch and the mean retention time (MRT) in 4 segments of the small intestine (proximal and distal jejunum and proximal and distal ileum) and in excreta, using chromic oxide as a marker. 3. Varietal differences in starch content (714–746 g starch/kg DM) were smaller than differences caused by crop N fertilisation (705–755 g starch/kg DM). Nitrogen application increased wheat crude protein (CP) content from 94 to 130 g/kg DM. 4. The majority of the ST in all diets was digested by the time the digesta reached the distal ileum (average 0·84 in the distal jejunum and 0·96 in the proximal ileum). 5. Starch digestion differed among wheat cultivars in the proximal jejunum (from 0·43 to 0·57, P < 0·001). Afterwards no differences due to wheat cultivar or N fertilisation were found. 6. Starch digestion rate varied among wheat cultivars (from 2·45 to 3·28 h−1, P < 0·001), but did not vary with N fertilisation, whereas dietary CP digestion rate was not affected by wheat cultivar or N fertilisation level. The digestion rate of ST was faster than that of CP (average 2·78 vs. 1·53 h−1). 7. The current study suggests that wheat cultivars can be classified on their rate of ST digestion independently of the N fertilisation applied to the crop during growth.
Four Superoxide Dismutases Contribute to Bacillus anthracis Virulence and Provide Spores with Redundant Protection from Oxidative Stress

ABSTRACT The Bacillus anthracis genome encodes four superoxide dismutases (SODs), enzymes capable of detoxifying oxygen radicals. That two of these SODs, SOD15 and SODA1, are present in the outermost layers of the B. anthracis spore is indicated by previous proteomic analyses of the exosporium. Given the requirement that spores must survive interactions with reactive oxygen species generated by cells such as macrophages during infection, we hypothesized that SOD15 and SODA1 protect the spore from oxidative stress and contribute to the pathogenicity of B. anthracis. To test these theories, we constructed a double-knockout (Δsod15 ΔsodA1) mutant of B. anthracis Sterne strain 34F2 and assessed its lethality in an A/J mouse intranasal infection model. The 50% lethal dose of the Δsod15 ΔsodA1 strain was similar to that of the wild type (34F2), but surprisingly, measurable whole-spore SOD activity was greater than that in 34F2. A quadruple-knockout strain (Δsod15 ΔsodA1 ΔsodC ΔsodA2) was then generated, and as anticipated, spore-associated SOD activity was diminished. Moreover, the quadruple-knockout strain, compared to the wild type, was attenuated more than 40-fold upon intranasal challenge of mice. Spore resistance to exogenously generated oxidative stress and to macrophage-mediated killing correlated with virulence in A/J mice. Allelic exchange that restored sod15 and sodA1 to their wild-type state restored wild-type characteristics. We conclude that SOD molecules within the spore afford B. anthracis protection against oxidative stress and enhance the pathogenicity of B. anthracis in the lung. We also surmise that the presence of four SOD alleles within the genome provides functional redundancy for this key enzyme.
Does spatial assimilation lead to reproduction of gentrification in the global city?

ABSTRACT In the political economy of place, cities can be thought of as global commodities marketed to the “creative class” and highly skilled immigrants, while privileged suburban spaces are protected by place stratification. The spatial assimilation literature shows that assimilated immigrants and minorities move to White, Anglo suburbs, resulting in some White succession. Is there a positive association between spatial assimilation and gentrification? How have populations in gentrifying neighborhoods and those experiencing spatial assimilation changed? This study answers these questions using ecological analysis and propensity score matching to analyze normalized census tract data from the National Neighborhood Change Database (1970–2010). Gentrification and spatial assimilation are correlated: the former as increased, whereas the latter has plateaued. Percentage White declined in both types of neighborhood. Gentrifying neighborhoods see an influx of Hispanic immigrants but no other immigrant populations. More barriers to spatial assimilation than to gentrification appear to remain, a finding consistent with place stratification theory.
Feasibility study of multipinhole collimators for high resolution small animal imaging

Multipinhole SPECT has the potential to overcome the inherent low efficiency of single pinhole gamma cameras typically used in small animal radionuclide imaging. By increasing the detector efficiency, multipinhole SPECT cameras allows to use reduced radionuclide dose and shorter scanning times than single pinhole gamma cameras. Reduced scanning times are advantageous for longitudinal studies where small animal models must be imaged several times. In addition, a spatial resolution of 1 mm or better is often required in drug delivery research and myocardial perfusion studies. In this article, we evaluate multipinhole collimator designs to obtain the best pinhole configuration that will increase the detector efficiency and maximize the use of a recently developed CZT with 128 times128 pixels. Additionally the multipinhole design minimize the overlap of the projection data to avoid artifacts in the tomographic reconstructions. For this purpose, we simulated the acquisition of projection data from point sources, microspheres phantoms, and resolution phantoms, by using a in house developed Monte Carlo program which accounts for the gamma photons interactions with the pinhole and detector crystal. The generated projection data was reconstructed using a standard ML-EM algorithm adapted for multipinhole radionuclide imaging. We determined the multipinhole collimator efficiency, resolution, and signal to noise ratio for several possible multipinhole configurations. A design of five pinhole arrays allowed high efficiency imaging (3.93 fold) while achieving a spatial resolution of 1 mm or better. Reconstruction of hot rod phantom data showed that a contrast of 90% between the hot rods and cold background was obtained after 45 iterations of the ML-EM algorithm.
The Effect of Remission of Poststroke Depression on Activities of Daily Living in a Double-Blind Randomized Treatment Study

Poststroke depression has been associated with impaired recovery of activities of daily living (ADL) during the first 2 years after stroke. This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind randomized treatment study. Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of 23 patients who met criteria for major depression (N = 16) or minor depression (N = 7) were selected and randomly assigned to either active treatment (nortriptyline) or placebo. Functional physical (i.e., ADL) impairment was assessed using the Johns Hopkins Functioning Inventory (JHFI). Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit. There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups, which would explain the significantly greater improvement among the remitted patients. Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication, nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery.
Focal agonist stimulation results in spatially restricted Ca2+ release and capacitative Ca2+ entry in bovine vascular endothelial cells

1 Intracellular Ca2+ ([Ca2+]i) signals were studied with spatial resolution in bovine vascular endothelial cells using the fluorescent Ca2+ indicator fluo‐3 and confocal laser scanning microscopy. Single cells were stimulated with the purinergic receptor agonist ATP resulting in an increase of [Ca2+]i due to intracellular Ca2+ release from inositol 1,4,5‐trisphosphate (IP3)‐sensitive stores. ATP‐induced Ca2+ release was quantal, i.e. submaximal concentrations mobilized only a fraction of the intracellularly stored Ca2+. 2 Focal receptor stimulation in Ca2+‐free solution by pressure application of agonist‐containing solution through a fine glass micropipette resulted in a spatially restricted increase in [Ca2+]i. Ca2+ release was initiated at the site of stimulation and frequently propagated some tens of micrometres into non‐stimulated regions. 3 Local Ca2+ release caused activation of capacitative Ca2+ entry (CCE). CCE was initially colocalized with Ca2+ release. Following repetitive focal stimulation, however, CCE became detectable at remote sites where no Ca2+ release had been observed. In addition, the rate of Ca2+ store depletion with repetitive local activation of release in Ca2+‐free solution was markedly slower than that elicited by ATP stimulation of the entire cell. 4 From these experiments it is concluded that both intracellular IP3‐dependent Ca2+ release and activation of CCE are controlled locally at the subcellular level. Moreover, redistribution of intracellular Ca2+ stored within the endoplasmic reticulum efficiently counteracts local store depletion and accounts for the spatial spread of CCE activation.
The “ups” and “downs” in Using Subtractive Cloning Techniques to Isolate Regulated Genes in Fish1

Abstract Over the last decade, subtractive cloning approaches have been used extensively to isolate genes that are up- or down-regulated under various conditions. These techniques have provided the foundation for many subsequent studies concerning gene function and regulation and, as such, have been valuable tools for many biological fields. Over the past 10 years, we have used different subtractive cloning approaches to isolate genes in fish that are regulated in relation to hormonal stimulation or the stage of ovarian maturation. These include conventional cDNA subtraction followed by library screening, differential display PCR, suppression subtraction hybridization, and more recently, iterative PCR subtraction. We continue to use these techniques for the isolation of new genes involved in physiological processes in fish and bivalve molluscs. Examples that illustrate the use of these different subtractive cloning techniques are described, including where possible the advantages and disadvantages of each. In addition, the use of ancillary methods (e.g., “Reverse Northerns”) to facilitate the use of these subtractive approaches are discussed.
A New Stock Market Model with Adaptive Rational Equilibrium Dynamics

We revise the simplest ARED stock market model, where heterogeneous beliefs on the future prices of a risky asset have first shown to be responsible of wild (chaotic) price fluctuations. Two often unrealistic scenarios, namely traders allowed to supply shares into the market and market clearing realized at negative prices, are here prevented by limiting traders' demands to nonnegative values and considering more realistic price predictions. The numerical analysis confirms that chaotic price fluctuations are expected when the intensity of traders' choice among the available price predictors is high.
Heart Rate Estimation From Wrist-Worn Photoplethysmography: A Review

Photoplethysmography (PPG) is a low-cost, non-invasive, and optical technique used to detect blood volume changes in the microvascular tissue bed, measured from the skin surface. It has traditionally been used in commercial medical devices for oxygen saturation, blood pressure monitoring, and cardiac activity for assessing peripheral vascular disease and autonomic function. There has been a growing interest to incorporate PPG sensors in daily life, capable of use in ambulatory settings. However, inferring cardiac information (e.g. heart rate) from PPG traces in such situations is extremely challenging, because of interferences caused by motion. Following the IEEE Signal Processing Cup in 2015, numerous methods have been proposed for estimating particularly the average heart rate using wrist-worn PPG during physical activity. Details on PPG technology, sensor development, and applications have been well documented in the literature. Hence, in this paper, we have presented a comprehensive review of state-of-the-art research on heart rate estimation from wrist-worn PPG signals. Our review also encompasses brief theoretical details about PPG sensing and other potential applications–biometric identification, disease diagnosis using wrist PPG. This paper will set a platform for future research on pervasive monitoring using wrist PPG.
Antioxidant activity of sestrin 2 controls neuropathic pain after peripheral nerve injury.

AIMS Neuropathic pain is a chronic debilitating disease that is often unresponsive to currently available treatments. Emerging lines of evidence indicate that reactive oxygen species (ROS) are required for the development and maintenance of neuropathic pain. However, little is known about endogenous mechanisms that neutralize the pain-relevant effects of ROS. In the present study, we tested whether the stress-responsive antioxidant protein Sestrin 2 (Sesn2) blocks the ROS-induced neuropathic pain processing in vivo. RESULTS We observed that Sesn2 mRNA and protein expression was up-regulated in peripheral nerves after spared nerve injury, a well-characterized model of neuropathic pain. Sesn2 knockout (Sesn2(-/-)) mice exhibited considerably increased late-phase neuropathic pain behavior, while their behavior in acute nociceptive and in inflammatory pain models remained unaffected. The exacerbated neuropathic pain behavior of Sesn2(-/-) mice was associated with elevated ROS levels and an enhanced activating transcription factor 3 up-regulation in sensory neurons, and it was reversed by the ROS scavenger N-tert-Butyl-α-phenylnitrone. In contrast, administration of the ROS donor tert-butyl hydroperoxide induced a prolonged pain behavior in naive Sesn2(-/-) mice. INNOVATION We show that the antioxidant function of Sesn2 limits neuropathic pain processing in vivo. CONCLUSION Sesn2 controls ROS-dependent neuropathic pain signaling after peripheral nerve injury and may, thus, provide a potential new target for the clinical management of chronic neuropathic pain conditions.