Miracle-dz/UniFAR-FTUs huggingface dataset:
Distribution of soluble guanylyl cyclase in the rat brain

The diffusible messenger nitric oxide (NO) acts in the brain largely through activation of soluble guanylyl cyclase (sGC), a heterodimer comprising α and β subunits. We used immunohistochemistry to study the distribution of both sGC subunits in the brain of adult rats. α and β subunits gave similar widespread staining throughout the CNS, which was strongest in neostriatum, olfactory tubercle, and supraoptic nucleus. Double‐labeling experiments showed striking cellular colocalization in most brain regions, suggesting that the two subunits may be organized into enzymatically active α/β heteromers. Mismatches were observed in cerebellar cortex: Purkinje cells and Bergmann glia were positive for both subunits, whereas granule cells and interneurons in the molecular layer were strongly immunopositive for β but only weakly stained for the α subunit. By using multiple labeling, we compared the localization of sGC with neuronal nitric oxide synthase (NOS‐I, the NO‐producing enzyme in neurons). In forebrain, the distribution of sGC and NOS‐I was complementary, with only occasional colocalization. In contrast, cellular colocalization was common in midbrain and cerebellum. These data support a widespread role for the NO/sGC/cGMP pathway in the CNS and suggest that, in addition to its role as paracrine messenger, NO may also be an intracellular autocrine agent. J. Comp. Neurol. 472:437–448, 2004. © 2004 Wiley‐Liss, Inc.
Cross Regulation of Sirtuin 1, AMPK, and PPARγ in Conjugated Linoleic Acid Treated Adipocytes

Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor γ (PPARγ) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPARγ, thereby inhibiting its activity. This study investigated the role of SIRT1 in the response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses: 1) SIRT1 is functionally required for robust TG reduction; and 2) SIRT1, AMPK, and PPARγ cross regulate each other. These experiments were performed by using activators, inhibitors, or siRNA knockdowns that affected these pathways in t10c12 CLA-treated 3T3-L1 adipocytes. Inhibition of SIRT1 amounts or activity using siRNA, sirtinol, nicotinamide, or etomoxir attenuated the amount of TG loss, while SIRT1 activator SRT1720 increased the TG loss. SRT1720 increased AMPK activity while sirtuin-specific inhibitors decreased AMPK activity. Reciprocally, an AMPK inhibitor reduced SIRT1 activity. Treatment with t10c12 CLA increased PPARγ phosphorylation in an AMPK-dependent manner and increased the amount of PPARγ bound to SIRT1. Reciprocally, a PPARγ agonist attenuated AMPK and SIRT1 activity levels. These results indicated SIRT1 increased TG loss and that cross regulation between SIRT1, AMPK, and PPARγ occurred in 3T3-L1 adipocytes treated with t10c12 CLA.
Discovery of biomarker combinations that predict periodontal health or disease with high accuracy from GCF samples based on high-throughput proteomic analysis and mixed-integer linear optimization.

AIM To identify optimal combination(s) of proteomic based biomarkers in gingival crevicular fluid (GCF) samples from chronic periodontitis (CP) and periodontally healthy individuals and validate the predictions through known and blind test sets. MATERIALS AND METHODS GCF samples were collected from 96 CP and periodontally healthy subjects and analysed using high-performance liquid chromatography, tandem mass spectrometry and the PILOT_PROTEIN algorithm. A mixed-integer linear optimization (MILP) model was then developed to identify the optimal combination of biomarkers which could clearly distinguish a blind subject sample as healthy or diseased. RESULTS A thorough cross-validation of the MILP model capability was performed on a training set of 55 samples and greater than 99% accuracy was consistently achieved when annotating the testing set samples as healthy or diseased. The model was then trained on all 55 samples and tested on two different blind test sets, and using an optimal combination of 7 human proteins and 3 bacterial proteins, the model was able to correctly predict 40 out of 41 healthy and diseased samples. CONCLUSIONS The proposed large-scale proteomic analysis and MILP model led to the identification of novel combinations of biomarkers for consistent diagnosis of periodontal status with greater than 95% predictive accuracy.
Model‐based clustering for social networks

Summary. Network models are widely used to represent relations between interacting units or actors. Network data often exhibit transitivity, meaning that two actors that have ties to a third actor are more likely to be tied than actors that do not, homophily by attributes of the actors or dyads, and clustering. Interest often focuses on finding clusters of actors or ties, and the number of groups in the data is typically unknown. We propose a new model, the latent position cluster model, under which the probability of a tie between two actors depends on the distance between them in an unobserved Euclidean ‘social space’, and the actors’ locations in the latent social space arise from a mixture of distributions, each corresponding to a cluster. We propose two estimation methods: a two‐stage maximum likelihood method and a fully Bayesian method that uses Markov chain Monte Carlo sampling. The former is quicker and simpler, but the latter performs better. We also propose a Bayesian way of determining the number of clusters that are present by using approximate conditional Bayes factors. Our model represents transitivity, homophily by attributes and clustering simultaneously and does not require the number of clusters to be known. The model makes it easy to simulate realistic networks with clustering, which are potentially useful as inputs to models of more complex systems of which the network is part, such as epidemic models of infectious disease. We apply the model to two networks of social relations. A free software package in the R statistical language, latentnet, is available to analyse data by using the model.
Tensor Encoding / Decoding :

INTRODUCTION In the first talk of the session, Dr Peter Basser will have introduced the theory of diffusion in biological systems and shown how, in tissue with ordered structure on the length scale of the measurement volume (i.e., voxel), diffusion appears anisotropic. In such cases, the diffusion properties cannot be fully characterized by a scalar value. The next most complex model of diffusion is the diffusion tensor – a 3 x 3 symmetrical positive definite matrix. In this presentation, we will focus on how the diffusion is estimated and how quantitative parameters are derived from the tensor, with focus on obtaining robust values. Pitfalls, artefacts and their remediation will be covered in the talk by Dr Carlo Pierpaoli, while sequences will be covered by Dr Jim Pipe.
Markov chains with quasitoeplitz transition matrix: applications

Application problems are investigated for the Markov chains with quasitoeplitz transition matrix. Generating functions of transient and steady state probabilities, first zero hitting probabilities and mean times are found for various particular cases, corresponding to some known patterns of feedback ( “warm-up,” “switch at threshold” etc.), Level depending dams and queue-depending queueing systems of both M/G/1 and MI/G/1 types with arbitrary random sizes of arriving and departing groups are studied.
An efficient energy saving mechanism for IEEE 802.16e wireless MANs

This paper presents an energy conservation scheme, maximum unavailability interval (MUI), to improve the energy efficiency for the Power Saving Class of Type II in IEEE 802.16e. By applying the Chinese remainder theorem, the proposed MUI is guaranteed to find the maximum Unavailability Interval, during which the transceiver can be powered down. The proposed MUI only dynamically adjusts one parameter defined in the standard. In addition, it is fully compatible with 802.16e standard. We also propose a new technique to reduce the computational complexity when solving the Chinese remainder theorem problem. Simulation and analysis have been conducted to evaluate the performance.
Mineralocorticoid Accelerates Transition to Heart Failure With Preserved Ejection Fraction Via “Nongenomic Effects”

Background— Mechanisms promoting the transition from hypertensive heart disease to heart failure with preserved ejection fraction are poorly understood. When inappropriate for salt status, mineralocorticoid (deoxycorticosterone acetate) excess causes hypertrophy, fibrosis, and diastolic dysfunction. Because cardiac mineralocorticoid receptors are protected from mineralocorticoid binding by the absence of 11-&bgr; hydroxysteroid dehydrogenase, salt-mineralocorticoid–induced inflammation is postulated to cause oxidative stress and to mediate cardiac effects. Although previous studies have focused on salt/nephrectomy in accelerating mineralocorticoid-induced cardiac effects, we hypothesized that hypertensive heart disease is associated with oxidative stress and sensitizes the heart to mineralocorticoid, accelerating hypertrophy, fibrosis, and diastolic dysfunction. Methods and Results— Cardiac structure and function, oxidative stress, and mineralocorticoid receptor–dependent gene transcription were measured in sham-operated and transverse aortic constriction (studied 2 weeks later) mice without and with deoxycorticosterone acetate administration, all in the setting of normal-salt diet. Compared with sham mice, sham plus deoxycorticosterone acetate mice had mild hypertrophy without fibrosis or diastolic dysfunction. Transverse aortic constriction mice displayed compensated hypertensive heart disease with hypertrophy, increased oxidative stress (osteopontin and NOX4 gene expression), and normal systolic function, filling pressures, and diastolic stiffness. Compared with transverse aortic constriction mice, transverse aortic constriction plus deoxycorticosterone acetate mice had similar left ventricular systolic pressure and fractional shortening but more hypertrophy, fibrosis, and diastolic dysfunction with increased lung weights, consistent with heart failure with preserved ejection fraction. There was progressive activation of markers of oxidative stress across the groups but no evidence of classic mineralocorticoid receptor–dependent gene transcription. Conclusions— Pressure-overload hypertrophy sensitizes the heart to mineralocorticoid excess, which promotes the transition to heart failure with preserved ejection fraction independently of classic mineralocorticoid receptor–dependent gene transcription.
Divide and conquer: the role of trust and assurance in the design of secure socio-technical systems

In order to be effective, secure systems need to be both correct (i.e. effective when used as intended) and dependable (i.e. actually being used as intended). Given that most secure systems involve people, a strategy for achieving dependable security must address both people and technology. Current research in Human-Computer Interactions in Security (HCISec) aims to increase dependability of the human element by reducing mistakes (e.g. through better user interfaces to security tools). We argue that a successful strategy also needs to consider the impact of social interaction on security, and in this respect trust is a central concept. We compare the understanding of trust in secure systems with the more differentiated models of trust in social science research. The security definition of "trust" turns out to map onto strategies that would be correctly described as "assurance" in the more differentiated model. We argue that distinguishing between trust and assurance yields a wider range of strategies for ensuring dependability of the human element in a secure socio-technical system. Furthermore, correctly placed trust can also benefit an organisation's culture and performance. We conclude by presenting design principles to help security designers decide "when to trust" and "when to assure", and give examples of how both strategies would be implemented in practice.
Distribution of sickness absence in the European Union countries

Aims: To determine the sickness absence frequency in European Union (EU) countries. Methods: Sickness absence was measured by questionnaire using the Third European Survey on Working Conditions. Employees were considered to have sickness absence if they reported to be absent at least one day in the past 12 months because of an accident at work, work related problems, or by other health problems. Results: Sickness absence percentages were lower in Southern European countries compared with Central and Northern European countries, and, in general, slightly higher in men than in women. Conclusion: This is the first description of sickness absence in each of the 15 EU countries. Examination of the sickness absence patterning between EU countries could indicate countries where important lessons to reduce sickness absence are to be learned and diffused across the EU.
The Social Neuroscience of Empathy

The phenomenon of empathy entails the ability to share the affective experiences of others. In recent years social neuroscience made considerable progress in revealing the mechanisms that enable a person to feel what another is feeling. The present review provides an in‐depth and critical discussion of these findings. Consistent evidence shows that sharing the emotions of others is associated with activation in neural structures that are also active during the first‐hand experience of that emotion. Part of the neural activation shared between self‐ and other‐related experiences seems to be rather automatically activated. However, recent studies also show that empathy is a highly flexible phenomenon, and that vicarious responses are malleable with respect to a number of factors—such as contextual appraisal, the interpersonal relationship between empathizer and other, or the perspective adopted during observation of the other. Future investigations are needed to provide more detailed insights into these factors and their neural underpinnings. Questions such as whether individual differences in empathy can be explained by stable personality traits, whether we can train ourselves to be more empathic, and how empathy relates to prosocial behavior are of utmost relevance for both science and society.
Analyzing DNA curvature and its impact on the ionic environment: application to molecular dynamics simulations of minicircles

Abstract We propose a method for analyzing the magnitude and direction of curvature within nucleic acids, based on the curvilinear helical axis calculated by Curves+. The method is applied to analyzing curvature within minicircles constructed with varying degrees of over- or under-twisting. Using the molecular dynamics trajectories of three different minicircles, we are able to quantify how curvature varies locally both in space and in time. We also analyze how curvature influences the local environment of the minicircles, notably via increased heterogeneity in the ionic distributions surrounding the double helix. The approach we propose has been integrated into Curves+ and the utilities Canal (time trajectory analysis) and Canion (environmental analysis) and can be used to study a wide variety of static and dynamic structural data on nucleic acids.
Estimation and Compensation for Lipschitz Nonlinear Discrete-Time Systems Subjected to Unknown Measurement Delays

Unknown measurement delays usually degrade system performance and even damage a system under output feedback control, which motivate us to develop an effective method to attenuate or offset the adverse effect from the measurement delays. In this paper, an augmented observer is proposed for discrete-time Lipschitz nonlinear systems subjected to unknown measurement delays, enabling a simultaneous estimation for system states and perturbed terms caused by output delays. On the basis of the estimates, a sensor compensation technique is addressed to remove the influence from the measurement delays to the system performance. Furthermore, an integrated robust estimation and compensation technique is proposed to decouple constant piecewise disturbances, attenuate other disturbances/noise, and offset the adverse effect caused by the measurement delays. The proposed methods are applied to a two-stage chemical reactor with delayed recycle and to an electromechanical servosystem, which demonstrate the effectiveness of the present techniques.
Evaluation of the NAL Dynamic Conversations Test in older listeners with hearing loss

Abstract Objective: The National Acoustic Laboratories Dynamic Conversations Test (NAL-DCT) is a new test of speech comprehension that incorporates a realistic environment and dynamic speech materials that capture certain features of everyday conversations. The goal of this study was to assess the suitability of the test for studying the consequences of hearing loss and amplification in older listeners. Design: Unaided and aided comprehension scores were measured for single-, two- and three-talker passages, along with unaided and aided sentence recall. To characterise the relevant cognitive abilities of the group, measures of short-term working memory, verbal information-processing speed and reading comprehension speed were collected. Study sample: Participants were 41 older listeners with varying degrees of hearing loss. Results: Performance on both the NAL-DCT and the sentence test was strongly driven by hearing loss, but performance on the NAL-DCT was additionally related to a composite cognitive deficit score. Benefits of amplification were measurable but influenced by individual test SNRs. Conclusions: The NAL-DCT is sensitive to the same factors as a traditional sentence recall test, but in addition is sensitive to the cognitive factors required for speech processing. The test shows promise as a tool for research concerned with real-world listening.
Rapid Physiological Fluctuations in Nucleus Accumbens Oxygen Levels Induced by Arousing Stimuli: Relationships with Changes in Brain Glucose and Metabolic Neural Activation

Proper entry of oxygen from arterial blood into the brain is essential for maintaining brain metabolism under normal conditions and during functional neural activation. However, little is known about physiological fluctuations in brain oxygen and their underlying mechanisms. To address this issue, we employed high-speed amperometry with platinum oxygen sensors in freely moving male rats. Recordings were conducted in the nucleus accumbens (NAc), a critical structure for sensorimotor integration. Rats were exposed to arousing stimuli of different nature (brief auditory tone, a 1-min novel object presentation, a 3-min social interaction with a conspecific, and a 3-min tail-pinch). We found that all arousing stimuli increased NAc oxygen levels. Increases were rapid (4–10-s onset latencies), modest in magnitude (1–3 μM or 5%–15% over baseline) and duration (5–20 min), and generally correlated with the arousing potential of each stimulus. Two strategies were used to determine the mechanisms underlying the observed increases in NAc oxygen levels. First, we showed that NAc oxygen levels phasically increase following intra-NAc microinjections of glutamate (GLU) that excite accumbal neurons. Therefore, local neural activation with subsequent local vasodilation is involved in mediating physiological increases in NAc oxygen induced by arousing stimuli. Second, by employing oxygen monitoring in the subcutaneous space, a highly-vascularized area with no metabolic activity, we determined that physiological increases in NAc oxygen also depend on the rise in blood oxygen levels caused by respiratory activation. Due to the co-existence of different mechanisms governing oxygen entry into brain tissue, NAc oxygen responses differ from fluctuations in NAc glucose, which, within a normal behavioral continuum, are regulated exclusively by neuro-vascular coupling due to glucose’s highly stable levels in the blood. Finally, we discuss the relationships between physiological fluctuations in NAc oxygen, glucose and metabolic brain activation assessed by intra-brain heat production.
Effect of posture on target acquisition with a trackball and touch screen

Computing devices are becoming more ubiquitous and are increasingly being used in unconventional environments and body postures. For example, more commonly computers are being used while standing up or walking slowly, such as with bank teller machines or hand-held devices. This paper investigates the effect of posture on Fitts' law and cursor position time in user interfaces when using a touch screen or trackball as the input device. Several experiments are described that measure the effect of standing and walking slowly during the interaction. Fitts' law was found to be an effective predictor of movement time across various targets sizes. Standing and walking did not have a significant negative effect on movement time when using a stylus, although a significant increase in error rate was discovered. However, when using a trackball in a standing posture, movement time and error rate both showed a significant increase. Based on these findings, touch screens appear to be more effective input devices for interactive systems that are used in non-sitting postures
In vivo transfer of a reporter gene into the ocular ciliary muscle mediated by ultrasound and microbubbles

Our goal is to assess the feasibility of low-intensity ultrasound (US) combined with echocontrast agent microbubbles (MB) to transfect the ciliary muscle which has previously been demonstrated to potentially allow the secretion of therapeutic proteins. Reporter plasmid DNA encoding Gaussia luciferase (pCMV-Gluc-1), containing the LacZ gene (pVAX1-LacZ), alone or mixed with 50 % microbubbles (Artison), were injected into the ciliary muscle of rat eyes, with or without ultrasound exposure. Animals were sacrificed 7 and 30 days after injection to assess the secreted luciferase into ocular fluids using luminometry. The localization of gene expression was investigated by β-galactosidase histochemistry, 7 days after transfection. At day 7, luciferase activity in ocular media was significantly higher in eyes injected with plasmid and treated with MB and US, as compared with eyes treated with US alone or with eyes injected with the plasmid only. US plus microbubbles showed a 2.6-fold increase in luminescence (p < 0.023) compared with the control non-US treated eyes. β-galactosidase expression was observed in the ciliary region in case of US and MB application, whereas no expression was observed in controls eyes without US application. We demonstrate for the first time the feasibility of in vivo gene transfer, mediated by ultrasound and microbubbles in the ciliary muscle for the intraocular production of secreted proteins in the ocular media.