julilili42/papers huggingface dataset:
Visualization of cGMP with cGi Biosensors
2013-01-01

Cyclic guanosine 3'-5'-monophosphate (cGMP) is an important signaling molecule in physiology, pathophysiology, and pharmacological therapy. It has been proposed that the functional outcome of an increase of cGMP in a given cell largely depends on the existence of global versus local cGMP pools. The recent development of genetically encoded fluorescent biosensors for cGMP is a major technical advance in order to monitor the spatiotemporal dynamics and compartmentalization of cGMP signals in living cells. Here we give an overview of the available cGMP sensors and how they can be used to visualize cGMP. The focus is on the fluorescence resonance energy transfer (FRET)-based cGi-type sensors (Russwurm et al., Biochem J 407:69-77, 2007), which are currently among the most useful tools for cGMP imaging in cells, tissues, and living organisms. We present detailed protocols that cover the entire imaging experiment, from the isolation of primary cells from cGi-transgenic mice and adenoviral expression of cGi sensors to the description of the setup required to record FRET changes in single cells and tissues. In-cell calibration of sensors and data evaluation is also described in detail and the limitations and common pitfalls of cGMP imaging are discussed. Specifically, we outline the use of FRET microscopy to visualize cGMP in murine smooth muscle cells (from aorta, bladder, and colon) and cerebellar granule neurons expressing cGi sensors. Most of the protocols can be easily adapted to other cell types and cGMP indicators and can be used as general guidelines for cGMP imaging in living cells, tissues and, eventually, whole organisms.
A toolbox for real-time subject-independent and subject-dependent classification of brain states from fMRI signals
2013-01-01

There is a recent increase in the use of multivariate analysis and pattern classification in prediction and real-time feedback of brain states from functional imaging signals and mapping of spatio-temporal patterns of brain activity. Here we present MANAS, a generalized software toolbox for performing online and offline classification of fMRI signals. MANAS has been developed using MATLAB, LIBSVM, and SVMlight packages to achieve a cross-platform environment. MANAS is targeted for neuroscience investigations and brain rehabilitation applications, based on neurofeedback and brain-computer interface (BCI) paradigms. MANAS provides two different approaches for real-time classification: subject dependent and subject independent classification. In this article, we present the methodology of real-time subject dependent and subject independent pattern classification of fMRI signals; the MANAS software architecture and subsystems; and finally demonstrate the use of the system with experimental results.
Semantic relations and compound transparency: A regression study in CARIN theory
2013-01-01

According to the CARIN theory of Gagn? and Shoben (1997), conceptual relations play an important role in compound interpretation. This study develops three measures gauging the role of conceptual relations, and pits these measures against measures based on latent semantic analysis (Landauer &amp; Dumais, 1997). The CARIN measures successfully predict response latencies in a familiarity categorization task, in a semantic transparency task, and in visual lexical decision. Of the measures based on latent semantic analysis, only a measure orthogonal to the conceptual relations, which instead gauges the extent to which the concepts for the compound?s head and the compound itself are discriminated, also reached significance. Results further indicate that in tasks requiring careful assessment of the meaning of the compound, general knowledge of conceptual relations plays a central role, whereas in the lexical decision task, attention shifts to co-activated meanings and the specifics of the conceptual relations realized in the compound?s modifier family.
Effect of Carbon Monoxide Donor CORM-2 on Vitamin D<sub>3</sub> Metabolism
2013-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt; (1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt;) by renal 25-hydroxyvitamin D&lt;sub&gt;3&lt;/sub&gt; 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; regulates Ca&lt;sup&gt;2+&lt;/sup&gt; and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; formation and klotho expression. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 μM CORM-2. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; plasma levels, renal &lt;i&gt;Cyp27b1&lt;/i&gt; gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased &lt;i&gt;Fgf23&lt;/i&gt; transcript levels. &lt;b&gt;&lt;i&gt;Conclusion: &lt;/i&gt;&lt;/b&gt;CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt; synthesis.
Electronic Approaches to Restitute Vision in Patients with Neurodegenerative Diseases of the Retina
2013-01-01

Degenerations of the outer retina are hereditary diseases leading to significant loss of vision. Several concepts of active electrical stimulation of the remaining retinal network resulted in the development of retinal visual implants and prosthetic vision. Subretinal and epiretinal visual implants are currently the leading approaches in restoring functional vision in blind humans with retinitis pigmentosa or other outer retinal degenerations. This review gives a short overview about the principles, advantages, limitations and vision outcome of the up-to-date published artificial vision by electronic visual implants, as well as their known biocompatibility and safety issues.
At the interface between organic radicals and TiO2(110) single crystals: electronic structure and paramagnetic character
2013-01-01

We find that in a paramagnetic pyrene derivative of the nitronyl nitroxide radical deposited on rutile TiO2(110) single crystals the molecules keep/lose their paramagnetic character depending on the local substrate hydroxylation. The first molecular layer may act as a "buffer" on which intact organic magnets are grown.
BDNF-dependent consolidation of fear memories in the perirhinal cortex
2013-01-01

In the recent years the perirhinal cortex (PRh) has been identified as a crucial brain area in fear learning. Since the neurotrophin brain-derived neurotrophic factor (BDNF) is an important mediator of synaptic plasticity and also crucially involved in memory consolidation of several learning paradigms, we analyzed now whether fear conditioning influences the expression of BDNF protein in the PRh. Here we observed a specific increase of BDNF protein 120 min after fear conditioning training. In order to test whether this increase of BDNF protein level is also required for the consolidation of the fear memory, we locally applied the Trk receptor inhibitor k252a into the PRh during this time window in a second series of experiments. By interfering with Trk-signaling during this critical time window, the formation of a long-term fear memory was completely blocked, indicated by a complete lack of fear potentiated startle 1 day later. In conclusion the present study further emphasizes the important role of the PRh in cued fear learning and identified BDNF as an important mediator for fear memory consolidation in the PRh.
Towards Optimizing Experiments for Maximum-confidence Model Selection between Different Soil-plant Models
2013-01-01

We present a method for experimental design, optimizing data acquisition for maximum confidence in the soil-plant model selection task. The method considers uncertainty in parameters, measurements and model structures. We combine Bayesian Model Averaging (BMA) with worth-of-data analysis and investigate how decisive the model weights are under different selections of data types. This allows assessing the power of different data types, data densities and data locations in identifying the best model structure from among a suite of plausible models. The models considered in this study are the crop models CERES, SUCROS, GECROS and SPASS, which are coupled to identical routines for simulating soil processes within the modeling framework Expert-N. The four models considerably differ in the degree of detail at which crop growth and root water uptake are represented. Monte-Carlo simulations were conducted for each of these models considering their uncertainty in soil hydraulic properties and selected crop model parameters. With Bayesian model updating by a Bootstrap filter, the models were then conditioned on field measurements of soil moisture, leaf area index (LAI), and evapotranspiration rates during a vegetation period of winter wheat in Nellingen, Southwestern Germany. Following our approach, we derived the BMA model weights when using all data or different subsets thereof. We discuss to which degree the posterior BMA mean outperformed the prior BMA mean and all individual posterior models, how informative the data types were for reducing prediction uncertainty of actual evapotranspiration, and how well the model structure can be identified based on the different data types and subsets.
Sensitivity to Auditory Spectral Width in the Fetus and Infant – An fMEG Study
2013-01-01

Auditory change detection is crucial for the development of the auditory system and a prerequisite for language development. In neonates, stimuli with broad spectral width like white noise (WN) elicit the highest response compared to pure tone and combined tone stimuli. In the current study we addressed for the first time the question how fetuses react to "WN" stimulation. Twenty-five fetuses (M age = 34.59 weeks GA, SD ± 2.35) and 28 healthy neonates and infants (M age = 37.18 days, SD ± 15.52) were tested with the first paradigm, wherein 500 Hz tones, 750 Hz tones, and WN segments were randomly presented and auditory evoked responses (AERs) were measured using fetal magnetoencephalography (fMEG). In the second paradigm, 12 fetuses (M age = 25.7 weeks GA, SD ± 2.4) and 6 healthy neonates (M age = 23 days and SD ± 6.2) were presented with two auditory oddball conditions: condition 1 consisted of attenuated WN as standard and 500 Hz tones and WN as deviants. In condition 2, standard 500 Hz tones were intermixed with WN and attenuated WN. AERs to volume change and change in spectral width were evaluated. In both paradigms, significantly higher AER amplitudes to WN than to pure tones replicated prior findings in neonates and infants. In fetuses, no significant differences were found between the auditory evoked response amplitudes of WN segments and pure tones (both paradigms). A trend toward significance was reached when comparing the auditory evoked response amplitudes elicited by attenuated WN with those elicited by WN (loudness change, second paradigm). As expected, we observed high sensibility to spectral width in newborns and infants. However, in the group of fetuses, no sensibility to spectral width was observed. This negative finding may be caused by different attenuation levels of the maternal tissue for different frequency components.
Intestinal Na<sup>+</sup> Loss and Volume Depletion in JAK3-Deficient Mice
2013-01-01

&lt;b&gt;&lt;i&gt;Background/Aims&lt;/i&gt;&lt;/b&gt;: The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na&lt;sup&gt;+&lt;/sup&gt; channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na&lt;sup&gt;+&lt;/sup&gt; exretion, blood pressure and extracellular fluid volume regulation. &lt;b&gt;&lt;i&gt;Methods&lt;/i&gt;&lt;/b&gt;: Experiments were performed in gene-targeted mice lacking functional JAK3 (&lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/-&lt;/i&gt;&lt;/sup&gt;) and in wild type mice (&lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt;). Colonic ENaC activity was estimated from amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na&lt;sup&gt;+&lt;/sup&gt; concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay. &lt;b&gt;&lt;i&gt;Results&lt;/i&gt;&lt;/b&gt;: The amiloride (50 μM)-induced deflection of the transepithelial potential difference was significantly lower and fecal Na&lt;sup&gt;+&lt;/sup&gt; excretion significantly higher in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/-&lt;/i&gt;&lt;/sup&gt; mice than in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; mice. Moreover, systolic arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/-&lt;/i&gt;&lt;/sup&gt; mice than in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; mice. Both, absolute and fractional renal Na&lt;sup&gt;+&lt;/sup&gt; excretion were significantly lower in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;-/-&lt;/i&gt;&lt;/sup&gt; mice than in &lt;i&gt;jak3&lt;/i&gt;&lt;sup&gt;&lt;i&gt;+/+&lt;/i&gt;&lt;/sup&gt; mice. &lt;b&gt;&lt;i&gt;Conclusions&lt;/i&gt;&lt;/b&gt;: JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na&lt;sup&gt;+&lt;/sup&gt; loss, decrease of blood pressure, increased aldosterone release and subsequent stimulation of renal tubular Na&lt;sup&gt;+&lt;/sup&gt; reabsorption.
Reliability assessment of safety-relevant automotive systems in a model-based design flow
2013-01-01

To support the reliability assessment of safety-relevant distributed automotive systems and reduce its complexity, this paper presents a novel approach that extends virtual prototyping towards error effect simulation. Besides the common functional and timed system simulation, error injection is used to stress error tolerance mechanisms. A quantitative assessment of the overall system reliability is performed by observing the system reactions and identifying incorrect system behavior. To foster the industrial application, the analysis is integrated in a model-based design flow, starting at the modeling level to assemble and parameterize the virtual prototype and to configure the analysis. The feasibility of the proposed approach is demonstrated by analyzing a representative safety-relevant automotive use case.
Are you a good mimic? Neuro-acoustic signatures for speech imitation ability
2013-01-01

We investigated individual differences in speech imitation ability in late bilinguals using a neuro-acoustic approach. One hundred and thirty-eight German-English bilinguals matched on various behavioral measures were tested for "speech imitation ability" in a foreign language, Hindi, and categorized into "high" and "low ability" groups. Brain activations and speech recordings were obtained from 26 participants from the two extreme groups as they performed a functional neuroimaging experiment which required them to "imitate" sentences in three conditions: (A) German, (B) English, and (C) German with fake English accent. We used recently developed novel acoustic analysis, namely the "articulation space" as a metric to compare speech imitation abilities of the two groups. Across all three conditions, direct comparisons between the two groups, revealed brain activations (FWE corrected, p < 0.05) that were more widespread with significantly higher peak activity in the left supramarginal gyrus and postcentral areas for the low ability group. The high ability group, on the other hand showed significantly larger articulation space in all three conditions. In addition, articulation space also correlated positively with imitation ability (Pearson's r = 0.7, p < 0.01). Our results suggest that an expanded articulation space for high ability individuals allows access to a larger repertoire of sounds, thereby providing skilled imitators greater flexibility in pronunciation and language learning.
In vitro Skin Permeation and Penetration of Nonivamide from Novel Film-Forming Emulsions
2013-01-01

The purpose of this study was to develop film-forming emulsions (FFE) facilitating long-term treatment of chronic pruritus with capsaicinoids. To this end, oil-in-water emulsions, which comprise dispersions of sustained-release polymers, were examined. Such emulsions form a film when applied to the skin and encapsulate the oily drug solution in a dry polymeric matrix. Permeation of the antipruritic drug nonivamide (NVA) is controlled by the matrix. Permeation rates of NVA from FFE and its concentration in the skin are equivalent to those achieved with a conventional semisolid formulation, but can be maintained for a longer period of time. FFE may therefore improve the treatment of chronic pruritus with capsaicinoids by enhancing patient compliance by means of a sustained-release regimen.
Suffixing, prefixing, and the functional order of regularities in meaningful strings
2013-01-01

The world?s languages tend to exhibit a suffixing preference, adding inflections to the ends of words, rather than the beginning of them. Previous works has suggested that this apparently universal preference arises out of the constraints imposed by general purpose learning mechanisms in the brain, and specifically, the kinds of information structures that facilitate discrimination learning (St Clair, Monaghan, &amp; Ramscar, 2009). Here I show that learning theory predicts that prefixes and suffixes will tend to promote different kinds of learning: prefixes will facilitate the learning of the probabilities that any following elements in a sequence will follow a label, whereas suffixing will promote the abstraction of common dimensions from a set of preceding elements. The results of the artificial language learning experiment support this analysis: When words are learned with consistent prefixes, participants learned the relationship between the prefixes and the noun labels, and the relationship between the noun labels and the objects associated with them, better than when words were learned with consistent suffixes. When words were learned with consistent suffixes, participants treated similarly suffixed nouns as being more similar than nouns learned with consistent prefixes. It appears that while prefixes tend to make items more predictable and to make veridical discriminations easier, suffixes tended to make items cohere more, increasing the similarities between them.
Habituation of reflexive and motivated behavior in mice with deficient BK channel function
2013-01-01

Habituation is considered the most basic form of learning. It describes the decrease of a behavioral response to a repeated non-threatening sensory stimulus and therefore provides an important sensory filtering mechanism. While some neuronal pathways mediating habituation are well described, underlying cellular/molecular mechanisms are not yet fully understood. In general, there is an agreement that short-term and long-term habituation are based on different mechanisms. Historically, a distinction has also been made between habituation of motivated versus reflexive behavior. In recent studies in invertebrates the large conductance voltage- and calcium-activated potassium (BK) channel has been implicated to be a key player in habituation by regulating synaptic transmission. Here, we tested mice deficient for the pore forming α-subunit of the BK channel for short-term and long-term habituation of the acoustic startle reflex (reflexive behavior) and of the exploratory locomotor behavior in the open field box (motivated behavior). Short-term habituation of startle was completely abolished in the BK knock-out mice, whereas neither long-term habituation of startle nor habituation of motivated behavior was affected by the BK deficiency. Our results support a highly preserved mechanism for short-term habituation of startle across species that is distinct from long-term habituation mechanisms. It also supports the notion that there are different mechanisms underlying habituation of motivated behavior versus reflexive behavior.
Immunology of Aging and Cancer Development
2013-01-01

The incidence and prevalence of most cancers increase with age. The immune system is a unique mechanism of defense against pathogens and possibly cancers, however there is a body of evidence that the immune system of the aged is eroded, a phenomenon termed immunosenescence. Each arm of the immune system, innate and adaptive, is altered with aging, contributing to increased tumorigenesis. Related to immunosenescence, a low-grade inflammation also develops with aging contributing also to increase carcinogenesis. Understanding the contribution of immunosenescence to cancer development and progression may lead to better interventions in the elderly.
25-Hydroxyvitamin D31-Alpha-Hydroxylase-Dependent Stimulation of Renal Klotho Expression by Spironolactone
2013-01-01

Besides blocking the effects of aldosterone, spironolactone upregulates KLOTHO gene expression by upregulation of 25-hydroxyvitamin D3 1-alpha-hydroxylase with subsequent activation of the vitamin D3 receptor by 1,25(OH)2D3, an effect possibly independent from the mineralocorticoid receptor.