Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Basis of the Effect of Potassium on Heterologously Expressed Pacemaker (HCN) Channels

Hyperpolarization‐activated cyclic‐nucleotide‐gated (HCN) channels modulate the firing rates of neuronal and cardiac pacemaker cells. HCN channels resemble voltage‐gated K+ channels structurally, but much less is known about their structure‐function correlation. Although modulation of K+ channel gating by external K+ is a well‐known phenomenon, such a link has not been established for HCN channels. Here we examined the effects of external permeant (K+, Na+ and Li+) and non‐permeant (NMG+) ions on HCN1 and HCN2 gating. Substituting 64 of 96 mm external K+ with Na+, Li+ or NMG+ positively shifted steady‐state activation (∼13 mV), and preferentially slowed activation of HCN1. Mutating the pore variant C‐terminal to the GYG motif in HCN1, A352, to the analogous conserved Asp in K+ channels or Arg in HCN2 produced a significant hyperpolarizing activation shift (by 5–15 mV), slowed gating kinetics (up to 6‐fold), and abolished or attenuated gating responses to external K+. Whereas Na+, Li+ and NMG+ substitutions produced depolarizing activation shifts of HCN2 similar to those of HCN1, deactivation but not activation of HCN2 was exclusively decelerated. We conclude that gating and permeation of HCN channels are coupled, and that modulation of this ‘pore‐to‐gate’ coupling by external K+ is isoform‐specific.
Technological Innovation: Concept, Process, Typology and Implications in the Economy

Growing interest worldwide to boost innovation in business sector activities, especially the technology, is intended to maintain or increase national economic competitiveness, inclusively as an effect of awareness concerning the effects resulting from economic activity on consumption of resources and environment, which requires design of new patterns of production and consumption. In this paper we review the most important contributions in the literature in terms of the implications of technological innovation in the economy, at the microand macroeconomic level, viewing the organization's ability to generate new ideas in support of increasing production, employment and environmental protection, starting from the concepts of innovation, innovation process and, respectively, from the innovation typology analysis.
Pulsed laser evaluation of single event transients in optocouplers

A methodology which used pulsed laser to evaluate the Single Event Transients (SETs) in the optocouplers was proposed. The SETs responses of the optocouplers were firstly investigated with the experimental simulation by pulsed laser test facility. The pulsed laser test data was compared with the ion test data to indicate the veracity and to provide insights into the SETs mechanism. The SETs characters induced by pulsed laser were qualitatively analyzed in model theory.
Prediction model for the characteristics of non-specular wave scattered from building surface

Wave propagation prediction models are crucial in determining propagation characteristics for any arbitrary installation on the implementation of a mobile radio communication system. The paper presents the development of simulation techniques for the estimation of wave propagation characteristics. It is based on a propagation prediction model of non-specular wave scattering from building surfaces. The method used to calculate the total field of the receiver antenna consists of four parts: calculate the far field pattern of the transmitter antenna; determine the equivalent current on the building surface; calculate the total field on the receiver antenna; obtain the multipath signal by applying ESPRIT. Numerical results show that the signal parameter profile is in good agreement with experimental results. However, a small difference is observed between the numerical and experimental results. The difference is attributed to the accuracy with which elements are discretized in the building surface roughness.
An individualized prognostic signature and multi-omics distinction for early stage hepatocellular carcinoma patients with surgical resection

Previously reported prognostic signatures for predicting the prognoses of postsurgical hepatocellular carcinoma (HCC) patients are commonly based on predefined risk scores, which are hardly applicable to samples measured by different laboratories. To solve this problem, using gene expression profiles of 170 stage I/II HCC samples, we identified a prognostic signature consisting of 20 gene pairs whose within-sample relative expression orderings (REOs) could robustly predict the disease-free survival and overall survival of HCC patients. This REOs-based prognostic signature was validated in two independent datasets. Functional enrichment analysis showed that the patients with high-risk of recurrence were characterized by the activations of pathways related to cell proliferation and tumor microenvironment, whereas the low-risk patients were characterized by the activations of various metabolism pathways. We further investigated the distinct epigenomic and genomic characteristics of the two prognostic groups using The Cancer Genome Atlas samples with multi-omics data. Epigenetic analysis showed that the transcriptional differences between the two prognostic groups were significantly concordant with DNA methylation alternations. The signaling network analysis identified several key genes (e.g. TP53, MYC) with epigenomic or genomic alternations driving poor prognoses of HCC patients. These results help us understand the multi-omics mechanisms determining the outcomes of HCC patients.
Multiple regions within EBNA1 can link DNAs

Epstein-Barr virus nuclear antigen 1 (EBNA1) can bind specifically to two clusters of sites within the Epstein-Barr virus plasmid origin of DNA replication (oriP). EBNA1 activates DNA replication mediated by oriP and can also activate transcription and retain DNA in cells when bound site specifically. EBNA1 bound to oriP physically links the two clusters of EBNA1-binding sites, resulting in loop formation by the intervening DNA. To elucidate the contribution of DNA linking by EBNA1 to its biological activities, we identified regions within it that can independently link DNAs to which they are bound. An electrophoretic mobility shift assay was used to detect this activity. Proteins which link DNA aggregate that DNA into large lattices. Proteins which cannot link DNA but still bind to DNA retard the mobility of that DNA but do not cause it to form lattices. Amino-terminal truncations were used to map the amino-terminal limit of a minimal DNA-linking domain approximately to amino acid 372 of EBNA1. To map the carboxy-terminal limit of this minimal domain, fusion proteins containing the DNA-binding domain of GAL4 and fragments of EBNA1 were generated and studied. This approach identified the carboxy-terminal limit of this minimal domain to be approximately amino acid 391 and verified its amino-terminal limit. Internal deletions within a truncated EBNA1 derivative verified the importance of this region. Two additional fragments of EBNA1, each of which independently conferred DNA-linking activity on the domain of GAL4 which binds DNA, were identified within amino acids 54 to 89 and amino acids 331 to 361. Therefore, EBNA1 contains at least three regions that can act independently to link DNAs and that may act in concert within intact EBNA1.
Insulin Modulates Neural Activity of Pyramidal Neurons in the Anterior Piriform Cortex

Insulin is an important peptide hormone that regulates food intake and olfactory function. While a multitude of studies investigated the effect of insulin in the olfactory bulb and olfactory epithelium, research on how it modulates higher olfactory centers is lacking. Here we investigate how insulin modulates neural activity of pyramidal neurons in the anterior piriform cortex, a key olfactory signal processing center that plays important roles in odor perception, preference learning, and odor pattern separation. In vitro we find from brain slice recordings that insulin increases the excitation of pyramidal neurons, and excitatory synaptic transmission while it decreases inhibitory synaptic transmission. In vivo local field potential (LFP) recordings indicate that insulin decreases both ongoing gamma oscillations and odor evoked beta responses. Moreover, recordings of calcium activity from pyramidal neurons reveal that insulin modulates the odor-evoked responses by an inhibitory effect. These results indicate that insulin alters olfactory signal processing in the anterior piriform cortex.
Effect of Interfacing between Spontaneous Breathing and Mechanical Cycles on the Ventilation‐Perfusion Distribution in Canine Lung Injury

BackgroundImproved matching between ventilation and perfusion (&OV0312;A/&OV0422;) has been proposed to be a major advantage of partial ventilatory support compared with controlled mechanical ventilation. This study was designed to determine whether a difference in gas exchange exists between partial ventilatory support techniques that allow unsupported spontaneous breathing to occur during any phase of the mechanical ventilatory cycle and those that provide mechanical support for each spontaneous inspiratory effort. MethodsTen anesthetized dogs with oleic acid-induced lung injury received, in random order, pressure-support ventilation (PSV) and airway pressure-release ventilation (APRV) with and without spontaneous breathing using equivalent airway pressure limits. Gas exchange was assessed by conventional blood gas analysis and by estimating the &OV0312;A/&OV0422; distributions using the multiple inert-gas elimination technique. ResultsDuring APRV, spontaneous breathing accounted for 10 ± 1% of the total expiratory minute ventilation. Breath-tobreath ventilatory support with PSV resulted in the highest total expiratory minute ventilation (P < 0.05). During spontaneous breathing with APRV, cardiac output increased from 3.9 ± 0.3 to 4.6 ± 0.41. min-1 (P< 0.05), arterial oxygen tension from 75 ± 3 to 107 ± 8 mmHg (P < 0.05), and oxygen delivery from 567 ± 47 to 719 ± 73 ml · kg min-1 (P < 0.05). PSV did not increase cardiac output, arterial oxygen tension, and oxygen delivery. Spontaneous breathing did not increase oxygen consumption. During APRV spontaneous breathing accounted for a 13 ± 2% decrease (P < 0.05) in blood flow to shunt units (&OV0312;A/&OV0422; < 0.005) and a 14 ± 2% increase (P < 0.05) in the perfusion of normal &OV0312;A/&OV0422; units (0.1 < &OV0312;A/&OV0422; < 10). Pulmonary blood flow distribution to shunt and normal &OV0312;A/&OV0422; units was similar during PSV and APRV without spontaneous breathing. Dead space (&OV0312;A/&OV0422; > 100) ventilation decreased by 6% during APRV with spontaneous breathing compared with PSV (P < 0.05). ConclusionsSpontaneous breathing superimposed on mechanical ventilation contributes to improved &OV0312;A/&OV0422; matching and increased systemic blood flow. Apparently, the spontaneous contribution to a mechanically assisted breath during PSV is not sufficient to counteract the &OV0312;A/&OV0422; maldistribution of positive pressure lung insufflation during acute lung injury.
Collective Behavior of Social Bots Is Encoded in Their Temporal Twitter Activity

Computational propaganda deploys social or political bots to try to shape, steer, and manipulate online public discussions and influence decisions. Collective behavior of populations of social bots has not been yet widely studied, although understanding of collective patterns arising from interactions between bots would aid social bot detection. In this study, we show that there are significant differences in collective behavior between population of bots and population of humans as detected from their Twitter activity. Using a large dataset of tweets we have collected during the UK-EU referendum campaign, we separated users into population of bots and population of humans based on the length of sequences of their high-frequency tweeting activity. We show that, while pairwise correlations between users are weak, they co-exist with collective correlated states; however the statistics of correlations and co-spiking probability differ in both populations. Our results demonstrate that populations of social bots and human users in social media exhibit collective properties similar to the ones found in social and biological systems placed near a critical point.
Fatigue and recovery of voluntary and electrically elicited dynamic force in humans.

1. Percutaneous electrical stimulation of the human quadriceps muscle has been used to assess the loss of central activation immediately after a bout of fatiguing exercise and during the recovery period. 2. Fatigue was induced in eight healthy males by a maximal effort lasting 25 s performed on an isokinetic cycle ergometer at a constant pedal frequency of 60 revolutions per minute. The cranks of the ergometer were driven by an electric motor. Before and after the sprint, subjects allowed their legs to be passively taken round by the motor. During the passive movement the knee extensors were stimulated (4 pulses; 100 Hz). Peak voluntary force (PVF) during the sprint and peak stimulated forces (PSF) before and in recovery were recorded via strain gauges in the pedals. Recovery of voluntary force was assessed in a series of separate experiments in which subjects performed a second maximal effort after recovery periods of different durations. 3. Peak stimulated forces were reduced to 69.8 +/‐ 9.3% immediately after the maximal effort, (P < 0.05), but had returned to pre‐exercise values after 3 min. The maximum rate of force development (MRFD) was also reduced following fatigue to 68.8 +/‐ 11.0% (P < 0.05) of control and was fully recovered after 2 min. PVF was reduced to 72.0 +/‐ 9.4% (P < 0.05) of the control value following the maximal effort. After 3 min voluntary force had fully recovered. 4. The effect of changing the duration of the fatiguing exercise (10, 25 and 45 s maximal effort) resulted in an increased degree of voluntary force loss as the duration of the maximal effort increased. (ABSTRACT TRUNCATED AT 250 WORDS)
Virion nucleic acid of Ebola virus

The virion nucleic acid of Ebola virus consists of a single-stranded RNA with a molecular weight of approximately 4.0 x 10(6). The virion RNA did not bind to oligodeoxythymidylic acid-cellulose under conditions known to bind RNAs rich in polyadenylic acid and was not infectious under conditions which yielded infectious RNA from Sindbis virus, suggesting that Ebola virus virion nucleic acid is a negative-stranded RNA.
Sagittarius A * High-energy X-Ray Flare Properties during NuStar Monitoring of the Galactic Center from 2012 to 2015

Understanding the origin of the flaring activity from the Galactic center supermassive black hole Sagittarius A* is a major scientific goal of the NuSTAR Galactic plane survey campaign. We report on the data obtained between 2012 July and 2015 April, including 27 observations on Sgr A*, with a total exposure of ≃ 1 Ms. We found a total of 10 X-ray flares detected in the NuSTAR observation window, with luminosities in the range of L 3 – 79 keV ∼ ( 0.2 – 4.0 ) × 10 35 erg s − 1 . With this largest hard X-ray Sgr A* flare data set to date, we studied the flare spectral properties. Seven flares are detected above 5 σ significance, showing a range of photon indices (Γ ∼ 2.0–2.8) with typical uncertainties of ±0.5 (90% confidence level). We found no significant spectral hardening for brighter flares, as indicated by a smaller sample. The accumulation of all of the flare spectra in 1–79 keV can be well fit with an absorbed power-law model with Γ = 2.2 ± 0.1 , and does not require the existence of a spectral break. The lack of variation in the X-ray spectral index with luminosity would point to a single mechanism for the flares and is consistent with the synchrotron scenario. Lastly, we present the quiescent-state spectrum of Sgr A*, and derive an upper limit on the quiescent luminosity of Sgr A* above 10 keV to be L Xq , 10 – 79 keV ≤ ( 2.9 ± 0.2 ) × 10 34 erg s−1.
Incompetency to stand trial: procedures, results, and problems.

We have described the breakdown of a vital social system necessitating collaboration between two highly respected professions. The confused statute regarding incompetency to stand trial and its distorted application by both physician and lawyer tends to subvert the social and legal principle inherent in the concept of competency and in so doing to sacrifice the professional identity of both lawyer and physician as well as their appropriate functions as assigned by society and which their client has the right to expect. In this process, the legal position becomes untenable. The court cannot use the psychiatrist effectively because it cannot understand him and because it does not demand that which could be understood. Therefore, in lieu of using his competence, it must accept his pronouncements and tacitly his usurpation of its role. The valued and traditional legal insistence on the right to determine fact is passively given over to the acceptance of opinion as fact. The result is that from start to finish.
SERUM GROWTH HORMONE BINDING PROTEIN ACTIVITY IN HEALTHY NEONATES, CHILDREN AND YOUNG ADULTS: CORRELATION WITH AGE, HEIGHT AND WEIGHT

Serum growth hormone binding protein (GHBP) activity was estimated in healthy neonates (n=6), children and adolescents (n=97) and young adults (n=19). GHBP activity was measured by incubating 125I‐hGH (human growth hormone) (˜ 25 000 c. p. m.) with serum (100 μ1) in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 1251‐hGHBP complexes from free 125I‐hGH by gel filtration on Ultrogel AcA44 minicolumns. The results are expressed as the percentage specific binding relative to an adult reference serum (%RSB), after correction for endogenous hGH of the unknown serum. The between‐assay coefficients of variation for two sera of %RSB activity of 51.2 and 115.4% were 6.0 and 7.0% respectively. In neonates, low values of serum GHBP were found (%RSB = 27.1 ± 5.0 SEM) followed by a major rise during the first 6 years of life to a mean value (%RSB = 68.3 ± 4.1 SEM) which more than doubled that of neonates. Thereafter, values rose progressively throughout childhood and puberty to reach maximum values in young adults (%RSB =95.0 ± 3.1 SEM). A novel observation was that serum GHBP activity correlated significantly with height standard deviation score (SDS) (males: r= 0.77, P < 0.001; females: r= 0.56, P= 0.01) and weight SDS (P < 0.001) for both sexes before puberty. During puberty GHBP correlated only with weight SDS in males (r=0.60, P < 0.01). In all age groups studied, no correlation could be found between serum GHBP and height velocity.
Prostaglandin Deficiency Promotes Sensitization of Adenylyl Cyclase

Abstract Inhibition of prostaglandin synthesis by the drug indomethacin suppresses the synthesis of the cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), and leads to a metabolic state comparable to type II diabetes. It was of interest whether prostaglandindeficiency likewise causes sensitization of adenylyl cyclase, as this has been reported for the diabetic state. In liver plasma membranes of indomethacintreated male rats, basal and forskolinstimulated cyclic AMP synthesis remained unchanged when compared to untreated control rats. In control rats, stimulation of cyclic AMP synthesis by fluoride (2.2-fold) or glucagon (3.5-fold) was much lower than stimulation by forskolin (6.6-fold). In contrast, in indomethacin treated rats, stimulation of cAMP synthesis by fluoride (4.6-fold) or glucagon (5.2-fold) nearly matched the stimulation by forskolin (6.4-fold). The level of α[1]adrenergic receptors was slightly reduced, from 450 to 320 fmol/mg protein, by the indomethacin treatment. Independent of the treatment by indomethacin, stimulation of cyclic AMP synthesis by adrenaline failed, in agreement with the low density of adrenergic βreceptors. In conclusion, PGE deficiency sensitizes adenylyl cyclase in rat liver for G proteincoupled receptors (glucagon) and also for fluoride.
Distribution Costs and International Business Cycles

Backus, Kehoe, and Kydland (International Real Business Cycles, JPE, 100(4), 1992) documented several discrepancies between the observed post-war business cycles of developed countries and the predictions of a two-country, complete-market model. The main discrepancy dubbed as the quantity anomaly, that cross-country consumption correlations are higher than that of output in the model as opposed to data, has remained a central puzzle in international economics. In order to resolve this puzzle mainly two strategies: restrictions on asset trade, and introducing non-traded goods in the model, have been employed by researchers. While these extensions have been successful in closing the gap to some extent, the ordering of correlations has stayed unchanged: consumption correlations still exceed that of output. This paper attempts to resolve the quantity puzzle by introducing non-traded distribution costs in the retailing of traded goods. In a simple two-good extension of the Backus, Kehoe, and Kydland model, it is shown that without distributions costs the cross-country consumption and output correlations are 0.55 and 0.30, respectively, whereas with distribution costs consumption correlation reduces to 0.09, output correlation to 0.23. Incorporating distribution costs, in addition, improves the models performance in matching the volatility of real exchange rates and the correlation of net exports with output. These improvements are achieved without sacriflcing the model’s performance in any other dimension.
Long-term results of expansive laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine: more than 10 years follow up.

OBJECT The authors report the long-term (more than 10-year) results of cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL) of the cervical spine as well as the factors affecting long-term postoperative course. METHODS The authors reviewed data obtained in 92 patients who underwent cervical laminoplasty between 1982 and 1990. Three patients were lost to follow up, 25 patients died within 10 years of surgery, and 64 patients were followed for more than 10 years. Results were assessed using the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy. The recovery rate was calculated using the Hirabayashi method. The mean neurological recovery rate during the first 10 years after surgery was 64%, which declined to 60% at the last follow-up examination (mean follow up 12.2 years). Late neurological deterioration occurred in eight patients (14%) from 5 to 15 years after surgery. The most frequent causes of late deterioration were degenerative lumbar disease (three patients), thoracic myelopathy secondary to ossification of the ligamentum flavum (two patients), or postoperative progression of OPLL at the operated level (two patients). Postoperative progression of the ossified lesion was noted in 70% of the patients, but only two patients (3%) were found to have related neurological deterioration. Additional cervical surgery was required in one patient (2%) because of neurological deterioration secondary to progression of the ossified ligament. The authors performed a multivariate stepwise analysis, and found that factors related to better clinical results were younger age at operation and less severe preexisting myelopathy. Younger age at operation, as well as mixed and continuous types of OPLL, was highly predictive of progression of OPLL. Postoperative progression of kyphotic deformity was observed in 8% of the patients, although it did not cause neurological deterioration. CONCLUSIONS When the incidence of surgery-related complications and the strong possibility of postoperative growth of OPLL are taken into consideration, the authors recommend expansive and extensive laminoplasty for OPLL.