Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular properties of voltage-sensitive sodium channels.

Voltage sensitive calcium channels participate in action potential generation in electrically excitable cells and constitute an essential link between transient changes in membrane potential and a variety of cellular responses including secretion of neurotransmitters and hormones, initiation of contraction in cardiac and smooth muscle, and activation of second messenger responses in many cell types. Electrophysiological measurements have established the existence of multiple classes of calcium channels.1–4 Although work on many cell systems has contributed to current understanding of calcium channel function, the molecular properties of the channel have been investigated most thoroughly in skeletal muscle which has a particularly high density of calcium channels. This chapter will therefore focus primarily on skeletal muscle calcium channels.
Flexoelectric Effect in Solids 1 Flexoelectric Effect in Solids

Piezoelectricity—the coupling between strain and electrical polarization, allowed 2 Zubko, Catalan, Tagantsev by symmetry in a restricted class of materials—is at the heart of many devices that permeate our daily life. Since its discovery in the 1880’s by Pierre and Jacques Curie, the piezoelectric effect has found use in everything from submarine sonars to cigarette lighters. By contrast, flexoelectricity—the coupling between polarization and strain gradients, allowed by symmetry in all materials—was largely overlooked for decades since its first proposal in the late 1950’s, due to the seemingly small magnitude of the effect in bulk. The development of nanoscale technologies, however, has renewed the interest in flexoelectricity, as the large strain gradients often present at the nanoscale can lead to dramatic flexoelectric phenomena. Here we review the fundamentals of the flexoelectric effect, discuss its presence in many nanoscale systems, and look at potential applications of this fascinating phenomenon. The review will also emphasize the many open questions and unresolved issues in this developing field.
Ground Plane influence on UTBB SOI nMOSFET analog parameters

This paper presents an analysis of the Ground Plane (GP) influence on analog parameters of Ultra Thin Body and Buried Oxide (UTBB) SOl nMOSFET devices based on experimental data and simulations results. The presence of a GP improves the transconductance in the saturation region due to the strong coupling between front and back gates. However, the GP worsens the output conductance due to the higher drain electrical field penetration observed by simulation. As a result, the devices without ground plane present better results in intrinsic voltage gain, Early Voltage and Drain Induced Barrier Lowering.
HISTONE DEACETYLASE6 Interacts with FLOWERING LOCUS D and Regulates Flowering in Arabidopsis1[C][W][OA]

Histone acetylation and deacetylation play an important role in epigenetic controls of gene expression. HISTONE DEACETYLASE6 (HDA6) is a REDUCED POTASSIUM DEPENDENCY3-type histone deacetylase, and the Arabidopsis (Arabidopsis thaliana) hda6 mutant axe1-5 displayed a late-flowering phenotype. axe1-5/flc-3 double mutants flowered earlier than axe1-5 plants, indicating that the late-flowering phenotype of axe1-5 was FLOWERING LOCUS C (FLC) dependent. Bimolecular fluorescence complementation, in vitro pull-down, and coimmunoprecipitation assays revealed the protein-protein interaction between HDA6 and the histone demethylase FLD. It was found that the SWIRM domain in the amino-terminal region of FLD and the carboxyl-terminal region of HDA6 are responsible for the interaction between these two proteins. Increased levels of histone H3 acetylation and H3K4 trimethylation at FLC, MAF4, and MAF5 were found in both axe1-5 and fld-6 plants, suggesting functional interplay between histone deacetylase and demethylase in flowering control. These results support a scenario in which histone deacetylation and demethylation cross talk are mediated by physical association between HDA6 and FLD. Chromatin immunoprecipitation analysis indicated that HDA6 bound to the chromatin of several potential target genes, including FLC and MAF4. Genome-wide gene expression analysis revealed that, in addition to genes related to flowering, genes involved in gene silencing and stress response were also affected in hda6 mutants, revealing multiple functions of HDA6. Furthermore, a subset of transposons was up-regulated and displayed increased histone hyperacetylation, suggesting that HDA6 can also regulate transposons through deacetylating histone.
Predominance of outcrossing in Lymnaea stagnalis despite low apparent fitness costs of self‐fertilization

We have quantified the natural mating system in eight populations of the simultaneously hermaphroditic aquatic snail Lymnaea stagnalis, and studied the ecological and genetic forces that may be directing mating system evolution in this species. We investigated whether the natural mating system can be explained by the availability of mates, by the differential survival of self‐ and cross‐fertilized snails in nature, and by the effects of mating system on parental fecundity and early survival. The natural mating system of L. stagnalis was found to be predominantly cross‐fertilizing. Density of snails in the populations had no relationship with the mating system, suggesting that outcrossing rates are not limited by mate availability at the population densities observed. Contrary to expectations for outcrossing species, we detected no evidence for inbreeding depression in survival in nature with inferential population genetic methods. Further, experimental manipulations of mating system in the laboratory revealed that self‐fertilization had no effect on parental fecundity, and only minor effects on offspring survival. Predominance of cross‐fertilization despite low apparent fitness costs of self‐fertilization is at odds with the paradigm that high self‐fertilization depression is necessary for maintenance of cross‐fertilization in self‐compatible hermaphrodites.
Onychomycosis in Children: Treatment with Bifonazole‐Urea

Abstract: We assessed the safety and efficacy of a two‐phase topical treatment with bifonazole‐urea ointment in children with onychomycosis. Twenty‐five children younger than 16 years old with proved onychomycosis were included in the study. Bifonazole‐urea ointment was administered under occlusion until the nontraumatic removal of the nail was achieved. Bifonazole cream was then applied for 4 weeks and a follow‐up visit 4 weeks after cessation of medication was scheduled. During the study, periodic clinical and mycologic evaluations were carried out. Of the 25 patients included, 17 were cured (68%), 6 improved, and 2 failed treatment. The main etiologic agent isolated was Trichophyton rubrum (92%). Two patients had minor side effects, both during the occlusive phase, one each with mild pain and a probable dermatitis from the adhesive strips. Treatment was not discontinued in both of these cases. We concluded that a two‐phase treatment with bifonazole‐urea is effective and safe, and represents a new therapeutic choice for onychomycosis in children.
Detection, Classification and Visualization of Anomalies using Generalized Entropy Metrics

Today, the Internet allows virtually anytime, anywhere acc ess to a seemingly unlimited supply of information and services. Statistics s uch as the six-fold increase of U.S. online retail sales since 2000 illustrate i ts growing importance to the global economy, and fuel our demand for rapid, ro und-the-clock Internet provision. This growth has created a need for syste m of control and management to regulate an increasingly complex infrast ructure. Unfortunately, the prospect of making fast money from this burgeoni ng industry has also started to attract criminals. This has driven an increa se in, and professionalization of, cyber-crime. As a result, a variety of methods have been designed with the intention of better protecting the Internet, its us ers and its underlying infrastructure from both accidental and malicious threats . Firewalls, which restrict network access, intrusion detection systems, whi ch locate and prevent unauthorized access, and network monitors, which over see the correct functioning of network infrastructures, have all been deve lop d in order to detect and avert potential problems. These systems can be br oadly defined as either reactive or proactive. The reactive approach seeks t o identify specific problem patterns. It uses models learnt from theory or pract ice to locate common dangers as they develop. The number of patterns applied g rows as each new problem is encountered. Proactive methods work differe ntly. They start defining an idealized model of the normal behavior of a given s ystem. Any significant deviation from this model is assumed to be an aber r nce caused by an external danger. However, this assumption may turn out to be incorrect, having actually not arisen from a disruption or a malicious a ct. Despite considerable improvements, the development of accurate proac tive detection and classification methods is still an area of intense research. This is particularly true of methods fit for high speed networks. To cope with the hu ge amounts of data at hand, these methods utilize highly aggregated forms f data. Volume
Usefulness of Routine Epicardial Pacing Wire Culture for Early Prediction of Poststernotomy Mediastinitis

ABSTRACT Poststernotomy mediastinitis (PSM) is one of the most serious complications of cardiac surgery, and its associated morbidity and mortality demand early recognition for emergency therapy. In this study, we investigated the usefulness of epicardial pacing wire (EPW) cultures for the prediction of PSM. Among 2,200 patients who underwent a cardiac surgical procedure at our hospital between 1 January 1999 and 31 December 2001, 82 (3.7%) had PSM; Staphylococcus aureus was the organism (45.1%) most frequently isolated at the time of surgical debridement. EPWs from 1,607 (73.0%) patients, 73 (4.5%) of whom developed PSM, were cultured. EPW cultures from 466 (29.0%) were positive, most often (74.9%) for coagulase-negative Staphylococci. EPW cultures were truly positive in 26 cases, truly negative in 1,106 cases, falsely positive in 428 cases, and falsely negative in 47 cases (with sterile cultures in 35 cases and a culture positive for an organism different from that isolated at the time of debridement in 12 cases). EPW culture had a positive predictive value of only 5.7% and a high negative predictive value (95.9%) for the diagnosis of PSM, with an accuracy of 70.4%. However, the likelihood ratio of positive (1.27) and negative (0.89) tests indicated only small changes in pretest-to-posttest probability. Therefore, a strategy of routine culture of EPWs to predict PSM seems questionable.
Profiling the effects of process changes on residual host cell proteins in biotherapeutics by mass spectrometry

An advanced liquid chromatography/mass spectrometry (MS) platform was used to identify and quantify residual Escherichia coli host cell proteins (HCPs) in the drug substance (DS) of several peptibodies (Pbs). Significantly different HCP impurity profiles were observed among different biotherapeutic Pbs as well as one Pb purified via multiple processes. The results can be rationally interpreted in terms of differences among the purification processes, and demonstrate the power of this technique to sensitively monitor both the quantity and composition of residual HCPs in DS, where these may represent a safety risk to patients. The breadth of information obtained using MS is compared to traditional multiproduct enzyme‐linked immunosorbent assay (ELISA) values for total HCP in the same samples and shows that, in this case, the ELISA failed to detect multiple HCPs. The HCP composition of two upstream samples was also analyzed and used to demonstrate that HCPs that carry through purification processes to be detectable in DS are not always among those that are the most abundant upstream. Compared to ELISA, we demonstrate that MS can provide a more comprehensive, and accurate, characterization of DS HCPs, thereby facilitating process development as well as more rationally assessing potential safety risks posed by individual, identified HCPs. © 2013 American Institute of Chemical Engineers Biotechnol. Prog. , 29:951–957, 2013
Current Trends in Research into the Waterborne Parasite Giardia

The waterborne flagellated parasite Giardia intestinalis continues to be the most frequent protozoan agent of intestinal disease world-wide, causing an estimated 2.8 x 108 cases per annum. Severe symptoms of diarrhea and sickness can be persistent and even life threatening in the immunocompromised, in infants, and in the aged, although self-limiting in the majority of patients. Despite a growing awareness and intensified research many uncertainties remain, especially with respect to the risk of potential zoonotic transmission. Water supplies can be monitored for cysts using automated cytofluorimetric immunoassays, but this does not measure infectivity. Filtration provides the best protection, because cysts are highly resistant to chlorine and ozone. Other incompletely elucidated aspects include mechanisms of pathogenicity, host reaction to infection, immunity and parasite control using vaccines or antigiardial compounds; the 5-nitroimidazole metronidazole is the most effective of these. Molecular typing of various isolates indicates that most animal parasites are not infective to humans, but those that are can be genotypically classified as assemblage A or B. The phylogeny of the organism remains uncertain, but there is a growing opinion that Giardia is not an ancient primitive eukaryote, but that it is derived from a more complex mitochondria-containing protozoon.
Involvement of the NADPH Oxidase NOX2–Derived Brain Oxidative Stress in an Unusual Fatal Case of Cocaine-Related Neurotoxicity Associated With Excited Delirium Syndrome

Abstract Here, we investigated the possible role of the Nicotinamide Adenine Dinucleotide Phosphate oxidase NOX2–derived brain oxidative stress in a fatal case of cocaine-related neurotoxicity, associated to excited delirium syndrome. We detected a strong NOX2 immunoreactivity, mainly in cortical GABAergic neurons and astrocytes, with a minor presence in microglia, glutamatergic and dopaminergic neurons as well as a significant immunostaining for other markers of oxidative stress (8OhDG, HSP70, HSP90, and NF-&kgr;B) and apoptotic phenomena. These results support a crucial role of NOX2-derived brain oxidative stress in cocaine-induced brain dysfunctions and neurotoxicity.
The association between rs4684677 T/A polymorphism in preproghrelin gene and predisposition to autoimmune thyroid diseases in children*

Abstract Background: A potential role of preproghrelin polymorphisms on autoimmune thyroid diseases (AITDs) has not been established equivocally yet. Aim: To estimate the association of two polymorphisms of preproghrelin gene with the predisposition to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in children. Methods: The study was performed in 145 patients with GD, 87 with HT and 161 healthy volunteers. The two single nucleotide polymorphisms (SNPs) rs696217 (C_3151003_20) and rs4684677 (C_25607748_10) in the preproghrelin gene were genotyped by TaqMan SNP genotyping assay using the real-time PCR. Results: Rs4684677 T alleles were more frequent in HT patients (99% in women and 100% in men) in comparison to healthy subjects (p = 0.002) with OR = 8.0 and 95% confidence interval for OR: 1.8–206.7. In women group, rs4684677 T alleles were more frequent compared to healthy controls (99%) in HT (p = 0.02) with OR = 6.7 and 95% confidence interval for OR: 1.2–168.37. Frequency of the SNP rs696217 did not differ between the groups. There was a significant relationship between rs696217 polymorphisms and anti-TSHR antibodies level (p = 0.036) in women from GD/HT groups. A significant relationship between rs696217 polymorphisms and anti-TG antibodies level in GD women group (p = 0.038) and between rs696217 polymorphisms and fT4 concentration (p = 0.03) were found. Conclusions: Rs4684677 T/A polymorphisms in preproghrelin gene could contribute to development of AITDs in children and T allele is the main risk factor.
Visualizing and Exploring Dynamic High-Dimensional Datasets with LION-tSNE

T-distributed stochastic neighbor embedding (tSNE) is a popular and prize-winning approach for dimensionality reduction and visualizing high-dimensional data. However, tSNE is non-parametric: once visualization is built, tSNE is not designed to incorporate additional data into existing representation. It highly limits the applicability of tSNE to the scenarios where data are added or updated over time (like dashboards or series of data snapshots). In this paper we propose, analyze and evaluate LION-tSNE (Local Interpolation with Outlier coNtrol) - a novel approach for incorporating new data into tSNE representation. LION-tSNE is based on local interpolation in the vicinity of training data, outlier detection and a special outlier mapping algorithm. We show that LION-tSNE method is robust both to outliers and to new samples from existing clusters. We also discuss multiple possible improvements for special cases. We compare LION-tSNE to a comprehensive list of possible benchmark approaches that include multiple interpolation techniques, gradient descent for new data, and neural network approximation.
Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O‐methylation of levodopa catalyzed by catechol‐O‐methyltransferase (COMT) that produces S‐adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT‐I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT‐I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT‐I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa‐treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT‐I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT‐I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT‐I effectively reduces HHcy. © 2004 Movement Disorder Society
Geophysical‐petrological model of the crust and upper mantle in the India‐Eurasia collision zone

We present a new crust and upper mantle cross section of the western India‐Eurasia collision zone by combining geological, geophysical, and petrological information within a self‐consistent thermodynamic framework. We characterize the upper mantle structure down to 410 km depth from the thermal, compositional, and seismological viewpoints along a profile crossing western Himalayan orogen and Tibetan Plateau, Tarim Basin, Tian Shan, and Junggar Basin, ending in the Chinese Altai Range. Our results show that the Moho deepens from the Himalayan foreland basin (~40 km depth) to the Kunlun Shan (~90 km depth), and it shallows to less than 50 km beneath the Tarim Basin. Crustal thickness between the Tian Shan and Altai mountains varies from ~66 km to ~62 km. The depth of the lithosphere‐asthenosphere boundary (LAB) increases from 230 km below the Himalayan foreland basin to 295 km below the Kunlun Shan. To NE the LAB shallows to ~230 km below the Tarim Basin and increases again to ~260 km below Tian Shan and Junggar region and to ~280 km below the Altai Range. Lateral variations of the seismic anomalies are compatible with variations in the lithospheric mantle composition retrieved from global petrological data. We also model a preexisting profile in the eastern India‐Eurasia collision zone and discuss the along‐strike variations of the lithospheric structure. We confirm the presence of a noticeable lithospheric mantle thinning below the Eastern Tibetan Plateau, with the LAB located at 140 km depth, and of mantle compositional differences between the Tibetan Plateau and the northern domains of Qilian Shan, Qaidam Basin, and North China.
Cardiogenic Shock : Results of the Impella Assist Device in Acute − Percutaneous

Michael Haude, Dierk Rulands, Christian Butter, Bengt Ullman, Laila Hellgren, Maria Grazia Cook, Stephan Windecker, Martin W. Bergmann, Roland Klingenberg, Thomas F. Lüscher, Alexander Lauten, Annemarie E. Engström, Christian Jung, Klaus Empen, Paul Erne, Stéphane EUROSHOCK-Registry − Cardiogenic Shock: Results of the Impella Assist Device in Acute − Percutaneous Left-Ventricular Support With the Impella-2.5 Print ISSN: 1941-3289. Online ISSN: 1941-3297 Copyright © 2012 American Heart Association, Inc. All rights reserved. 75231 is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Circulation: Heart Failure doi: 10.1161/CIRCHEARTFAILURE.112. 967224 2013;6:23-30; originally published online December 4, 2012; Circ Heart Fail. http://circheartfailure.ahajournals. org/content/6/1/23 World Wide Web at: The online version of this article, along with updated information and services, is located on the
Carbachol‐induced changes in excitability and [Ca2+]i signalling in projection cells of medial entorhinal cortex layers II and III

The entorhinal cortex (EC) is a major gateway for sensory information into the hippocampus and receives a cholinergic input from the forebrain. Therefore, we studied muscarinic effects on excitability and intracellular Ca2+ signalling in layer II stellate and layer III pyramidal projection neurons of the EC. In both classes of neurons, local pressure‐pulse application of carbachol (1 mm) caused small, atropine‐sensitive membrane depolarizations that were not accompanied by any detectable changes in [Ca2+]i. At a higher concentration (10 mm), carbachol induced a larger membrane depolarization associated with synaptic oscillations and epileptiform activity in both classes of neurons. In contrast to the intrinsic theta rhythm in stellate cells with one dominant peak frequency at ∼ 7 Hz, the synaptically mediated oscillation induced by carbachol showed three characteristic peaks in the theta and gamma frequency range at ∼ 11, 23 and 40 Hz. Although carbachol‐induced epileptiform activity was associated with increases in intracellular free Ca2+ in both layer II and III cells, the observed [Ca2+]i accumulation was significantly larger in layer III than in layer II cells. Responses to intracellular current injections showed differences in Ca2+ accumulation in layer II and III cells at the same membrane potentials, suggesting a dominant expression of low‐ and high‐voltage‐activated Ca2+ channels in these layer II and III cells, respectively. In conclusion, we present evidence for significant differences in the [Ca2+]i regulation between layer II stellate and layer III pyramidal cells of the medial EC.