Improving cuff-less continuous blood pressure estimation with linear regression analysis

In this work, the authors investigate the cuff-less estimation of continuous BP through pulse transit time (PTT) and heart rate (HR) using regression techniques, which is intended as a first step towards continuous BP estimation with a low error, according to AAMI guidelines. Hypertension (the 'silent killer') is one of the main risk factors for cardiovascular diseases (CVDs), which are the main cause of death worldwide. Its continuous monitoring can offer a valid tool for patient care, as blood pressure (BP) is a significant indicator of health and, using it together with other parameters, such as heart and breath rates, could strongly improve prevention of CVDs. The novelties introduced in this work are represented by the implementation of pre-processing and by the innovative method for features research and features processing to continuously monitor blood pressure in a non-invasive way. Currently, invasive methods are the only reliable methods for continuous monitoring, while non-invasive techniques measure the values every few minutes. The proposed approach can be considered the first step for the integration of these types of algorithms on wearable devices, in particular on those developed for the SINTEC project

Relation between parasites, reproductive index and habitat change in Rock Partridge (Alectoris graeca) populations in the central Southern Alps.

Relation between parasites, reproductive index and habitat change in Rock Partridge (Alectoris graeca) populations in the central southern alps. FABRO C.1, VISINTIN A.1, FILACORDA S.1, FRANGIPANE DI REGALBONO A.2, ARTUSO I.3 1Department of Agriculture and Environmental Sciences \u2013 University of Udine 2Department of Experimental Veterinary Science- University of Padua 3Comprensorio Alpino N\ub01 Val Brembana Hunting district Within the hunting district of Val Brembana the presence of parasites along the intestinal tract in 60 individuals (32 adults and 22 juveniles, 6 indeterminate) has been studied and correlated to the reproductive indexes (R.I, measured on 3 and 6 years) of Rock Partridges Alectoris graeca saxatilis in 6 different sectors and the habitat change. Within these sectors the coverage (%) of several environmental classes in different sample areas has been identified through photo interpretation over a time interval of 25 years. In the whole area a high spread of the nematode Ascaridia was observed and high values of prevalence (P = 69.49%) and mean abundance (MA = 15.21) have been found, while the presence of genus Capillaria was low with MA = 0.17 and P = 13.56%. Heterakis was isolated in 33.90% of the Rock Partridges, with MA = 1.45. For Ascaridia and Heterakis the relationship between variance and mean abundance (s2/MA) was significantly greater than one (Ascarids = 48.94; Heterakis: 7.90) and the aggregation index k (s2 / (s2-MA) ) was very close to zero, proving that these parasites show a highly aggregated distribution within host populations. When analyzing separately the 2 age classes there seemed to be no significant difference in parasitic infection susceptibility between juveniles (P = 95.45%) and adults (P = 84.95%). Only MA and P of Heterakis in different sectors was negatively correlated to a change in reproductive success, both in short and medium term, while the sectors with the greatest MA of Ascaridia, both in short and medium term, showed the highest mean reproductive rates and the sectors with the highest k of Capillaria had the highest R.I. The presence of parasites and particularly the value of MA of Capillaria and the average total number of parasites seemed to increase with the decreasing of open areas (coverage) in the different sectors of the study area, as well as with the decreasing of this observed coverage throughout the 25 year period. A negative correlation between open areas and the s2/AM ratio was discovered to be very clear. The presence of open areas seemed to affect significantly the abundance of parasites that in turn seemed to only partially drive R.I changes. The research was supported by Comprensorio Alpino N\ub0 1 Val Brembana Hunting district

Stochastic model of hysteresis

The methods of the probability theory have been used in order to build up a new model of hysteresis. It turns out that the reversal points of the control parameter (e. g., the magnetic field) are Markov points which determine the stochastic evolution of the process. It has been shown that the branches of the hysteresis loop are converging to fixed limit curves when the number of cyclic back-and-forth variations of the control parameter between two consecutive reversal points is large enough. This convergence to limit curves gives a clear explanation of the accommodation process. The accommodated minor loops show the return-point memory property but this property is obviously absent in the case of non-accommodated minor loops which are not congruent and generally not closed. In contrast to the traditional Preisach model the reversal point susceptibilities are non-zero finite values. The stochastic model can provide a good approximation of the Raylaigh quadratic law when the external parameter varies between two sufficiently small values.Comment: 13 pages, 14 figure

Functional Integration Approach to Hysteresis

A general formulation of scalar hysteresis is proposed. This formulation is based on two steps. First, a generating function g(x) is associated with an individual system, and a hysteresis evolution operator is defined by an appropriate envelope construction applied to g(x), inspired by the overdamped dynamics of systems evolving in multistable free energy landscapes. Second, the average hysteresis response of an ensemble of such systems is expressed as a functional integral over the space G of all admissible generating functions, under the assumption that an appropriate measure m has been introduced in G. The consequences of the formulation are analyzed in detail in the case where the measure m is generated by a continuous, Markovian stochastic process. The calculation of the hysteresis properties of the ensemble is reduced to the solution of the level-crossing problem for the stochastic process. In particular, it is shown that, when the process is translationally invariant (homogeneous), the ensuing hysteresis properties can be exactly described by the Preisach model of hysteresis, and the associated Preisach distribution is expressed in closed analytic form in terms of the drift and diffusion parameters of the Markovian process. Possible applications of the formulation are suggested, concerning the interpretation of magnetic hysteresis due to domain wall motion in quenched-in disorder, and the interpretation of critical state models of superconducting hysteresis.Comment: 36 pages, 9 figures, to be published on Phys. Rev.

mRNA Display Design of Fibronectin-based Intrabodies That Detect and Inhibit Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein

The nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) coronavirus plays important roles in both viral replication and modulation of host cell processes. New ligands that target the N protein may thus provide tools to track the protein inside cells, detect interaction hot spots on the protein surface, and discover sites that could be used to develop new anti-SARS therapies. Using mRNA display selection and directed evolution, we designed novel antibody-like protein affinity reagents that target SARS N protein with high affinity and selectivity. Our libraries were based on an 88-residue variant of the 10th fibronectin type III domain from human fibronectin (10Fn3). This selection resulted in eight independent 10Fn3 intrabodies, two that require the N-terminal domain for binding and six that recognize the C terminus, one with K_d = 1.7 nM. 10Fn3 intrabodies are well expressed in mammalian cells and are relocalized by N in SARS-infected cells. Seven of the selected intrabodies tested do not perturb cellular function when expressed singly in vivo and inhibit virus replication from 11- to 5900-fold when expressed in cells prior to infection. Targeting two sites on SARS-N simultaneously using two distinct 10Fn3s results in synergistic inhibition of virus replication

Semen analysis of G olden R etriever healthy dogs and those affected by muscular dystrophy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106077/1/and12079.pd

Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Big conductance calcium-activated potassium channel openers control spasticity without sedation.

BACKGROUND AND PURPOSE: Our initial aim was to generate cannabinoid agents that control spasticity, occurring as a consequence of multiple sclerosis (MS), whilst avoiding the sedative side effects associated with cannabis. VSN16R was synthesized as an anandamide (endocannabinoid) analogue in an anti-metabolite approach to identify drugs that target spasticity. EXPERIMENTAL APPROACH: Following the initial chemistry, a variety of biochemical, pharmacological and electrophysiological approaches, using isolated cells, tissue-based assays and in vivo animal models, were used to demonstrate the activity, efficacy, pharmacokinetics and mechanism of action of VSN16R. Toxicological and safety studies were performed in animals and humans. KEY RESULTS: VSN16R had nanomolar activity in tissue-based, functional assays and dose-dependently inhibited spasticity in a mouse experimental encephalomyelitis model of MS. This effect occurred with over 1000-fold therapeutic window, without affecting normal muscle tone. Efficacy was achieved at plasma levels that are feasible and safe in humans. VSN16R did not bind to known CB1 /CB2 /GPPR55 cannabinoid-related receptors in receptor-based assays but acted on a vascular cannabinoid target. This was identified as the major neuronal form of the big conductance, calcium-activated potassium (BKCa ) channel. Drug-induced opening of neuronal BKCa channels induced membrane hyperpolarization, limiting excessive neural-excitability and controlling spasticity. CONCLUSIONS AND IMPLICATIONS: We identified the neuronal form of the BKCa channel as the target for VSN16R and demonstrated that its activation alleviates neuronal excitability and spasticity in an experimental model of MS, revealing a novel mechanism to control spasticity. VSN16R is a potential, safe and selective ligand for controlling neural hyper-excitability in spasticity