Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced external counterpulsation improved myocardial perfusion and coronary flow reserve in patients with chronic stable angina; evaluation by(13)N-ammonia positron emission tomography.

AIMS The mechanism by which enhanced external counterpulsation therapy exerts its beneficial effects on chronic and symptomatic stable angina is largely unknown. To clarify the mechanism of action of enhanced external counterpulsation, we used(13)N-ammonia positron emission tomography to evaluate myocardial perfusion. METHODS AND RESULTS This was not a randomized controlled study. Eleven patients (eight male, age: 61.6+/-9.7) with angina pectoris underwent enhanced external counterpulsation therapy for 35 1 h sessions. They underwent a treadmill exercise test and(13)N-ammonia positron emission tomography, both at rest and with dipyridamole, before and after enhanced external counterpulsation therapy. Neurohumoral factors and nitric oxide were also evaluated. Myocardial perfusion increased at rest after therapy (0.69+/-0.27 to 0.85+/-0.47 ml x min(-1) x g(-1), P<0.05). In ischaemic regions, particularly the anterior region, myocardial perfusion at rest and with dipyridamole and coronary flow reserve improved significantly after therapy (at rest: 0.71+/-0.26 to 0.86+/-0.31;P<0.05, with dipyridamole: 1.26+/-0.65 to 1.84+/-0.94;P<0.02, coronary flow reserve: 1.75+/-0.24 to 2.08+/-0.28;P<0.04). Exercise time was prolonged and the time to 1-mm ST depression improved markedly (P<0.01). After therapy, nitric oxide levels increased (P<0.02) and neurohumoral factors decreased. CONCLUSIONS Enhanced external counterpulsation therapy improved myocardial perfusion at rest and with dipyridamole and was associated with an increased exercise tolerance with(13)N-ammonia positron emission tomography and increased nitric oxide levels. These results suggest that one of the enhanced external counterpulsation mechanisms is development and recruitment of collateral vessels.
SCIENTIFIC HIGHLIGHT OF THE MONTH 21 1 Electronic Correlations from First Principles ? 21 2 Calculating effective local Coulomb interactions from first principles : from

We propose a mechanism for binding of diatomic ligands to heme based on a dynamical orbital selection process. This scenario may be described as bonding determined by local valence fluctuations. We support this model using linear-scaling first-principles calculations, in combination with dynamical mean-field theory, applied to heme, the kernel of the hemoglobin metalloprotein central to human respiration. We find that variations in Hunds exchange coupling induce a reduction of the iron 3d density, with a concomitant increase of valence fluctuations. We discuss the comparison between our computed optical absorption spectra and experimental data, our picture accounting for the observation of optical transitions in the infrared regime, and how the Hunds coupling reduces, by a factor of 5, the strong imbalance in the binding energies of heme with CO and O2 ligands. Phys. Rev. Lett. 110, 106402 (2013). Contact person: Cédric Weber (cedric.weber@kcl.ac.uk)
The impact of solubility and electrostatics on fibril formation by the H3 and H4 histones

The goal of this study was to examine fibril formation by the heterodimeric eukaryotic histones (H2A‐H2B and H3‐H4) and homodimeric archaeal histones (hMfB and hPyA1). The histone fold dimerization motif is an obligatorily domain‐swapped structure comprised of two fused helix:β‐loop:helix motifs. Domain swapping has been proposed as a mechanism for the evolution of protein oligomers as well as a means to form precursors in the formation of amyloid‐like fibrils. Despite sharing a common fold, the eukaryotic histones of the core nucleosome and archaeal histones fold by kinetic mechanisms of differing complexity with transient population of partially folded monomeric and/or dimeric species. No relationship was apparent between fibrillation propensity and equilibrium stability or population of kinetic intermediates. Only H3 and H4, as isolated monomers and as a heterodimer, readily formed fibrils at room temperature, and this propensity correlates with the significantly lower solubility of these polypeptides. The fibrils were characterized by ThT fluorescence, FTIR, and far‐UV CD spectroscopies and electron microscopy. The helical histone fold comprises the protease‐resistant core of the fibrils, with little or no protease protection of the poorly structured N‐terminal tails. The highly charged tails inhibit fibrillation through electrostatic repulsion. Kinetic studies indicate that H3 and H4 form a co‐fibril, with simultaneous incorporation of both histones. The potential impact of H3 and H4 fibrillation on the cytotoxicity of extracellular histones and α‐synuclein‐mediated neurotoxicity and fibrillation is considered.
Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory*

Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFNγ or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFNγ- and IL4-responsive genes through inhibiting NFκB/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies.
Joint Detection and Estimation of Multiple Objects From Image Observations

The problem of jointly detecting multiple objects and estimating their states from image observations is formulated in a Bayesian framework by modeling the collection of states as a random finite set. Analytic characterizations of the posterior distribution of this random finite set are derived for various prior distributions under the assumption that the regions of the observation influenced by individual objects do not overlap. These results provide tractable means to jointly estimate the number of states and their values from image observations. As an application, we develop a multi-object filter suitable for image observations with low signal-to-noise ratio (SNR). A particle implementation of the multi-object filter is proposed and demonstrated via simulations.
Low FEV1, smoking history, and obesity are factors associated with oxygen saturation decrease in an adult population cohort

Background Worsening of pulmonary diseases is associated with a decrease in oxygen saturation (SpO2). Such a decrease in SpO2 and associated factors has not been previously evaluated in a general adult population. Aim We sought to describe SpO2 in a sample of adults, at baseline and after 6.3 years, to determine whether factors predicting low SpO2 in a cross-sectional study were also associated with a decrease in SpO2 in this cohort. Methods As part of the Tromsø Study, 2,822 participants were examined with pulse oximetry in Tromsø 5 (2001/2002) and Tromsø 6 (2007/2008). Low SpO2 by pulse oximetry was defined as an SpO2 ≤95%, and SpO2 decrease was defined as a ≥2% decrease from baseline to below 96%. Results A total of 139 (4.9%) subjects had a decrease in SpO2. Forced expiratory volume in 1 second (FEV1) <50% of the predicted value and current smoking with a history of ≥10 pack-years were the baseline characteristics most strongly associated with an SpO2 decrease in multivariable logistic regression (odds ratio 3.55 [95% confidence interval (CI) 1.60–7.89] and 2.48 [95% CI 1.48–4.15], respectively). Male sex, age, former smoking with a history of ≥10 pack-years, body mass index ≥30 kg/m2, and C-reactive protein ≥5 mg/L were also significantly associated with an SpO2 decrease. A significant decrease in FEV1 and a new diagnosis of asthma or chronic obstructive pulmonary disease during the observation period most strongly predicted a fall in SpO2. A lower SpO2 decrease was observed in those who quit smoking and those who lost weight, but these tendencies were not statistically significant. Conclusion A decrease in SpO2 was most strongly associated with severe airflow limitation and a history of smoking. Smoking cessation and reducing obesity seem to be important measures to target for avoiding SpO2 decreases in the general population.
Constraining dark matter properties with SPI

Using the high-resolution spectrometer SPI on board the International Gamma-Ray Astrophysics Laboratory (INTEGRAL) , we search for a spectral line produced by a dark matter (DM) particle with a mass in the range40keV < M D M < 14M eV , decaying in the DM halo of the Milky Way. To distinguish the DM decay line from numerous instrumental lines found in the SPI background spectrum, we study the dependence of the intensity of the line signal on the offset of the SPI pointing from the direction toward th e Galactic Centre. After a critical analysis of the uncertainties of the DM density profile in the inner Galaxy, we find that the intensity of the DM decay line should decrease by at least a factor of 3 when the offset from the Galactic Centre increases from 0 � to 180 � . We find that such a pronounced variation of the line flux across the sky is not observed for any line, detec ted with a significance higher than 3� in the SPI background spectrum. Possible DM decay origin is not ruled out only for the unidentified spectral lines, having low ( � 3�) significance or coinciding in position with the instrumental ones. In the energy interval from 20 keV to 7 MeV, we derive restrictions on the DM decay line flux, implied by the (non-)detection of the D M decay line. For a particular DM candidate, the sterile neutrino of mass M D M , we derive a bound on the mixing angle.
Square loop frequency selective surface with wide-passband properties using multi-period structures

The frequency selective surface (FSS) with ultra-wide passband performance and a sharp rejection near the side of the passband is investigated in this paper. The proposed cascaded FSS consists of a 2-D periodic array of square loop aperture (SLA) and an array of bandstop square loop (SL) with different period. Under different incident waves, the proposed second-order FSS and third-order FSS provide 3 dB relative bandwidth 114% and 125%, which achieve wider bandwidth in comparison with the previously proposed structures.
A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents.

RATIONALE Pulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary arterial muscularization due to excessive pulmonary vascular cell proliferation and migration, a phenotype dependent upon growth factors and activation of receptor tyrosine kinases (RTKs). p130(Cas) is an adaptor protein involved in several cellular signaling pathways that control cell migration, proliferation, and survival. OBJECTIVES We hypothesized that in experimental and human PAH p130(Cas) signaling is overactivated, thereby facilitating the intracellular transmission of signal induced by fibroblast growth factor (FGF)2, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). MEASUREMENTS AND MAIN RESULTS In patients with PAH, levels of p130(Cas) protein and/or activity are higher in the serum, in the walls of distal pulmonary arteries, in cultured smooth muscle cells (PA-SMCs), and in pulmonary endothelial cells (P-ECs) than in control subjects. These abnormalities in the p130(Cas) signaling were also found in the chronically hypoxic mice and monocrotaline-injected rats as models of human PAH. We obtained evidence for the convergence and amplification of the growth-stimulating effect of the EGF-, FGF2-, and PDGF-signaling pathways via the p130(Cas) signaling pathway. We found that daily treatment with the EGF-R inhibitor gefitinib, the FGF-R inhibitor dovitinib, and the PDGF-R inhibitor imatinib started 2 weeks after a subcutaneous monocrotaline injection substantially attenuated the abnormal increase in p130(Cas) and ERK1/2 activation and regressed established pulmonary hypertension. CONCLUSIONS Our findings demonstrate that p130(Cas) signaling plays a critical role in experimental and idiopathic PAH by modulating pulmonary vascular cell migration and proliferation and by acting as an amplifier of RTK downstream signals.
Overaccumulation, Public Debt and the Importance of Land

Abstract In recent contributions, von Weizsäcker (2014) and Summers (2014) maintain that mature economies accumulate too much capital. They suggest large and lasting public deficits as a remedy. This study argues that overaccumulation cannot occur in an economy with land. It presents novel data of aggregate land values, analyzes the issue within a stochastic framework and conducts an empirical test of overaccumulation.
The effect of flight‐related behaviour on the risk of venous thrombosis after air travel

In a case–control study including 11 033 participants (The Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on risk factors of venous thrombosis, we studied the effect of flight‐related behaviour on the risk of venous thrombosis after air travel. Patients and control subjects received a questionnaire on risk factors for venous thrombosis, including recent travel history and details of their last flight. From this population, 80 patients and 108 control subjects were selected who had recently (<8 weeks) travelled for more than 4 h by aeroplane. Window seating compared to aisle seating increased the risk twofold [odds ratio (OR) 2·2; 95% confidence interval (CI): 1·1–4·4], particularly in those who were obese (OR 6·1; 95% CI: 0·5–76·2). Anxiety (OR 2·5; 95% CI: 0·9–7·0) and sleeping (OR 1·5; 95% CI: 0·7–3·1) may increase the risk slightly. The risk was not affected by alcohol consumption (OR 1·1; 95% CI: 0·5–2·4). Flying business class may lower the risk (OR 0·7; 95% CI: 0·2–1·8). We did not find a protective effect for several measures currently part of standard advice from airlines and clinicians, i.e. drinking non‐alcoholic beverages, exercising or wearing stockings. The effect of behavioural factors during flying on the risk of venous thrombosis after air travel is limited. Current advice on prevention of travel‐related thrombosis may have to be reconsidered.
Factorial Structure of the Sensation-Seeking Scale-Form V: Confirmatory Factorial Analyses in Nonclinical and Clinical Samples

Objective: The factor structure of the Sensation-Seeking Scale (SSS)-Form V was studied in 2 large French samples, using confirmatory factorial analyses (CFA) to test the 4-dimensional model of sensation seeking postulated by Zuckerman. Method: The study included 769 healthy subjects and 659 patients who met the DSM-IV criteria for substance use disorders or eating disorders and completed the SSS. The correlation matrices for each of the samples were analyzed using CFA. Results: In each sample, we found the 4-factor model to be replicable. Conclusion: The multidimensionality of sensation seeking is supported by the results, and the 4-dimensional model of sensation seeking identified by Zuckerman can be explored in French-speaking people.
Cooperative Cognitive Intelligence for Internet of Vehicles

To resolve the contradictions between the increasing demand of vehicular wireless applications and the shortage of spectrum resources, high mobility, short link lifetime, and spectrum efficiency, a novel cognitive radio (CR) and efficient management of spectrum in vehicular communication is required. Therefore, to exhibit the importance of spectral efficiency, a system model is proposed for cooperative centralized and distributed spectrum sensing in vehicular networks. The proposed architecture is used to minimize both the spectral scarcity and high mobility issues. Furthermore, we analyze the decision fusion techniques in cooperative spectrum sensing for vehicular networks. In addition, a system model is designed for decision fusion techniques using renewal theory, and then, we analyze the probability of detection of primary channel and the average waiting time for CR user or secondary user in PU transmitter. Finally, mathematical analysis is performed to check the probability of detection and false alarm. The results show that the cooperative cognitive model is more suitable for vehicular networks that minimize interference and hidden PU problem.
Genomic models predict successful coral adaptation if future ocean warming rates are reduced

Population genomic simulations predict coral adaptation only under mitigated climate change scenarios. Population genomic surveys suggest that climate-associated genetic variation occurs widely across species, but whether it is sufficient to allow population persistence via evolutionary adaptation has seldom been quantified. To ask whether rapid adaptation in reef-building corals can keep pace with future ocean warming, we measured genetic variation at predicted warm-adapted loci and simulated future evolution and persistence in a high-latitude population of corals from Rarotonga, Cook Islands. Alleles associated with thermal tolerance were present but at low frequencies in this cooler, southerly locality. Simulations based on predicted ocean warming in Rarotonga showed rapid evolution of heat tolerance resulting in population persistence under mild warming scenarios consistent with low CO2 emission plans, RCP2.6 and RCP4.5. Under more severe scenarios, RCP6.0 and RCP8.5, adaptation was not rapid enough to prevent extinction. Population adaptation was faster for models based on smaller numbers of additive loci that determine thermal tolerance and for higher population growth rates. Finally, accelerated migration via transplantation of thermally tolerant individuals (1 to 5%/year) sped adaptation. These results show that cool-water corals can adapt to warmer oceans but only under mild scenarios resulting from international emissions controls. Incorporation of genomic data into models of species response to climate change offers a promising method for estimating future adaptive processes.
Training Contracts, Worker Overconfidence, and the Provision of Firm-Sponsored General Training

Training by firms is a central means by which workers accumulate human capital, yet firms may be reluctant to provide general training if workers can quit and use their gained skills elsewhere. ``Training contracts" that impose a penalty for premature quitting can help alleviate this inefficiency. Using two exogenously staggered contract changes at a leading trucking firm, we show that training contracts significantly reduce post-training quitting and increase the profitability of training. We demonstrate further that training contracts have especially large effects on training profits in our setting because of their interaction with worker overconfidence. If workers are overconfident about their own productivity at the current firm relative to their outside option, they will be more likely to sign training contracts and less likely to quit after training. Combining weekly productivity data with weekly productivity beliefs, we show that workers systematically overpredict their productivity, both with and without randomized financial incentives for accurate prediction. To quantify the impact of overconfidence for optimal contracts and welfare, we develop and estimate a structural learning model with biased beliefs that accounts for many key features of the data. Eliminating worker overconfidence would moderately increase worker welfare by 1.7%, but would decrease training profits by over $8,000 per truck and substantially alter the optimal training contract. We confirm the feasibility of reducing overconfidence using an information experiment at a second large trucking firm. Despite the positive effect of training contracts on profits, training may not be profitable unless workers are overconfident.
Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome.

BACKGROUND AND OBJECTIVES Up to 95% of children presenting with steroid-resistant nephrotic syndrome in early life will have a pathogenic single-gene mutation in 1 of 24 genes currently associated with this disease. Others may be affected by polymorphic variants. There is currently no accepted diagnostic algorithm for clinical genetic testing. The hypothesis was that the increasing reliability of next generation sequencing allows comprehensive one-step genetic investigation of this group and similar patient groups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study used next generation sequencing to screen 446 genes, including the 24 genes known to be associated with hereditary steroid-resistant nephrotic syndrome. The first 36 pediatric patients collected through a national United Kingdom Renal Registry were chosen with comprehensive phenotypic detail. Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing. RESULTS Analysis revealed known and novel disease-associated variations in expected genes such as NPHS1, NPHS2, and PLCe1 in 19% of patients. Phenotypically unexpected mutations were also detected in COQ2 and COL4A4 in two patients with isolated nephropathy and associated sensorineural deafness, respectively. The presence of an additional heterozygous polymorphism in WT1 in a patient with NPHS1 mutation was associated with earlier-onset disease, supporting modification of phenotype through genetic epistasis. CONCLUSIONS This study shows that next generation sequencing analysis of pediatric steroid-resistant nephrotic syndrome patients is accurate and revealing. This analysis should be considered part of the routine genetic workup of diseases such as childhood steroid-resistant nephrotic syndrome, where the chance of genetic mutation is high but requires sequencing of multiple genes.
Hypoxia augments the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice

The molecular identity of calcium‐activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin‐1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs).