Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6–8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved into a new flock.
Towards user-defined multi-touch gestures for 3D objects

Although multi-touch interaction in 2D has become widespread on mobile devices, intuitive ways to interact with 3D objects has not been thoroughly explored. We present a study on natural and guided multi-touch interaction with 3D objects on a 2D multi-touch display. Specifically, we focus on interactions with 3D objects that have either rotational, tightening, or switching components on mechanisms that might be found in mechanical operation or training simulations. The results of our study led to the following contributions: a classification procedure for determining the category and nature of a gesture, an initial user-defined gesture set for multi-touch gestures applied to 3D objects, and user preferences with regards to metaphorical versus physical gestures.
Partial state and unknown input estimation for time-delay systems

This article considers the problem of estimating a partial set of the state vector and/or unknown input vector of linear systems driven by unknown inputs and time-varying delay in the state variables. Three types of reduced-order observers, namely, observers with delays, observers without internal delays and delay-free observers are proposed in this article. Existence conditions and design procedures are presented for the determination of parameters for each case of observers. Numerical examples are presented to illustrate the design procedures.
Neuropeptide Y Promotes Neurogenesis in Murine Subventricular Zone

Stem cells of the subventricular zone (SVZ) represent a reliable source of neurons for cell replacement. Neuropeptide Y (NPY) promotes neurogenesis in the hippocampal subgranular layer and the olfactory epithelium and may be useful for the stimulation of SVZ dynamic in brain repair purposes. We describe that NPY promotes SVZ neurogenesis. NPY (1 μM) treatments increased proliferation at 48 hours and neuronal differentiation at 7 days in SVZ cell cultures. NPY proneurogenic properties are mediated via the Y1 receptor. Accordingly, Y1 receptor is a major active NPY receptor in the mouse SVZ, as shown by functional autoradiography. Moreover, short exposure to NPY increased immunoreactivity for the phosphorylated form of extracellular signal‐regulated kinase 1/2 in the nucleus, compatible with a trigger for proliferation, whereas 6 hours of treatment amplified the phosphorylated form of c‐Jun‐NH2‐terminal kinase signal in growing axons, consistent with axonogenesis. NPY, as a promoter of SVZ neurogenesis, is a crucial factor for future development of cell‐based brain therapy.
Markov decision problems and state-action frequencies

Consider a controlled Markov chain with countable state and action spaces. Basic quantities that determine the values of average cost functionals are identified. Under some regularity conditions, these turn out to be a collection of numbers, one for each state-action pair, describing for each state the relative number of uses of each action. These "conditional frequencies," which are defined pathwise, are shown to determine the "state-action frequencies" that, in the finite case, are known to determine the costs. This is extended to the countable case, allowing for unbounded costs. The space of frequencies is shown to be compact and convex, and the extreme points are identified with stationary deterministic policies. Conditions under which the search for optimality in several optimization problems may be restricted to stationary policies are given. These problems include the standard Markov decision process, as well as constrained optimization (both in terms of average cost functionals) and variability-sensitive optimization. An application to a queueing problem is given, where these results imply the existence and explicit computation of optimal policies in constrained optimization problems. The pathwise definition of the conditional frequencies implies that their values can be controlled directly; moreover, they depend only on the limiting behavior of the control. This has immediate application to adaptive control of Markov chains, including adaptive control under constraints.
NMR‐based insights into the conformational and interaction properties of Arkadia RING‐H2 E3 Ub ligase

Arkadia (Rnf111), an E3 Ubiquitin (Ub) ligase, amplifies TGF‐β signaling responses by targeting for degradation of the negative regulators Smad6/7 and the SnoN/Ski transcriptional repressors when they block the TGF‐β effectors Smad2/3. The E3 ligase activity of Arkadia depends on its C‐terminal RING‐H2 domain that constitutes the docking site for the E2 Ub‐conjugating enzyme carrying the activated Ub. We determined the nuclear magnetic resonance solution structure of Arkadia's RING‐H2 domain and revealed a (β)ββα fold, fully consistent with the expected “cross‐brace” mode of Zn(II)‐ligation. In addition, the interaction of the Arkadia RING‐H2 domain with its E2 partner enzyme (UbcH5b) was examined through chemical shift perturbation. Proteins 2012. © 2012 Wiley Periodicals, Inc.
Axial and Radial Forces of Cross-Bridges Depend on Lattice Spacing

Nearly all mechanochemical models of the cross-bridge treat myosin as a simple linear spring arranged parallel to the contractile filaments. These single-spring models cannot account for the radial force that muscle generates (orthogonal to the long axis of the myofilaments) or the effects of changes in filament lattice spacing. We describe a more complex myosin cross-bridge model that uses multiple springs to replicate myosin's force-generating power stroke and account for the effects of lattice spacing and radial force. The four springs which comprise this model (the 4sXB) correspond to the mechanically relevant portions of myosin's structure. As occurs in vivo, the 4sXB's state-transition kinetics and force-production dynamics vary with lattice spacing. Additionally, we describe a simpler two-spring cross-bridge (2sXB) model which produces results similar to those of the 4sXB model. Unlike the 4sXB model, the 2sXB model requires no iterative techniques, making it more computationally efficient. The rate at which both multi-spring cross-bridges bind and generate force decreases as lattice spacing grows. The axial force generated by each cross-bridge as it undergoes a power stroke increases as lattice spacing grows. The radial force that a cross-bridge produces as it undergoes a power stroke varies from expansive to compressive as lattice spacing increases. Importantly, these results mirror those for intact, contracting muscle force production.
Continuity of Care for Older Adults with Chronic Illness in China: An Exploratory Study.

OBJECTIVE To explore nurses' understanding of continuity of care and existing problems in implementation of continuity of care for Chinese elders with chronic illnesses. DESIGN AND SAMPLE Cross-sectional survey and semi-structured interview were performed on 15 nurses and older patients and 1,902 older patients between July 2010 and February 2011. MEASURES Semi-structured interview guideline and four-section scale were used. RESULTS The interviews showed nurses lacked knowledge of continuity of care, and nurses from small towns or rural areas had less understanding of continuity of care and discharge planning than nurses from central cities. Significant differences were found among patients located in referred areas in selection of medical institutions for treatment, suggesting older adults were more likely to choose general hospitals for treatment. Self-reported surveys demonstrated more than 70% of hospitalized elders chose community hospitals for further recovery after discharge from general hospitals. CONCLUSIONS Chinese nurses lack knowledge of continuity of care, and significant discontinuity exists between health care provided by general hospitals, community hospitals and other institutions for elders. A further model for the development of continuity of care should be established that addresses older patients' demands and current barriers in China.
Investigation of Seismic Response of Reinforced Soil Retaining Walls

Dynamic response of a segmental (modular block) retaining wall system to recorded ground motions is investigated. The magnitude and characteristics of wall response are compared to those obtained under harmonic input base acceleration. The calculated maximum lateral displacement and reinforcement load of the segmental retaining wall mode1 subjected to a single frequency, harmonic input acceleration were considerably larger than the corresponding values obtained using a number of earthquake accelerograms with comparable predominant frequencies. It is concluded that the random characteristic of actual ground acceleration may partly explain the relatively good performance of reinforced-soil retaining wall systems that were designed without seismic considerations or at best using simple pseudo-static limit equilibrium methods. Nevertheless, it was found that low-frequency ground motions with high intensity values can result in significant structural response magnitude of short-period retaining wall systems.
Restoring soil functions by means of cyanobacteria inoculation: Importance of soil conditions and species selection

In recent years, soil inoculation with cyanobacteria has become one of the most promising biotechnological strategies for restoring soil functionality in degraded drylands because of their critical role in increasing soil fertility and preventing erosion. Nevertheless, in order to fully exploit this biotechnology on a large scale, it must still be shown whether inoculated cyanobacteria are capable of developing in soils with different physicochemical properties, and new candidates adapted to desert conditions must be explored. To evaluate the potential of cyanobacteria for restoring soil functions of degraded dryland soils, in this laboratory study, we analyzed the effect of inoculating three native N‐fixing species (Nostoc commune, Scytonema hyalinum, and Tolypothrix distorta), individually and as a consortium, on soil properties from three different semiarid ecosystems in southeast Spain. The biocrust colonization was monitored by determining chlorophyll a content (the typical surrogate used for biocrust biomass). Other methodologies, such as the analysis of soil spectral response and image classification were also applied for cover estimation of the biocrust. After 3 months, all inoculated soils showed cyanobacteria cover of up to 50%, lower albedo and higher chlorophyll a content. Cyanobacterial inoculation also improved soil functions, as they promoted a significant gain in total organic carbon and total nitrogen in all soils. Among inoculation treatments, Nostoc commune and the mixture of all three species promoted the most cyanobacteria coverage, chlorophyll content, and surface darkening, as well as organic carbon and total nitrogen gains in the soil, highlighting their excellent performance in biocrust development.
Small-Signal Characterization of Acoustic Resonances in Low-Wattage Metal Halide Lamps

In this paper a detailed study about acoustic resonance in low-wattage metal halide lamps is presented. In order to analyze the acoustic resonance behavior, the lamps are supplied by DC current and a controlled variable-frequency small-signal is superposed. By using this method, theoretical and experimental resonances can be compared, verifying their amplitudes, and the threshold power value for their excitation. Besides, this analysis is done for same lamps with different operation hours, in order to verify its influence in the resonance behavior
Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid arthritis. A randomised single blinded controlled trial.

OBJECTIVE Local cryotherapy is used to relieve pain and inflammation in injuries and inflammatory conditions. Whole-body cryotherapy is an extreme method administered at -110 degrees C for 2 to 3 minutes. The aim of the study was to compare the effect of cryotherapies on pain and inflammation in patients with rheumatoid arthritis (RA). METHODS Sixty patients with active seropositive RA were recruited in a randomised controlled single-blinded study to receive whole-body cryotherapy at -110 degrees C, whole-body cryotherapy at -60 degrees C, application of local cold air at -30 degrees C and the use of cold packs locally. In the final analysis, the last 2 groups were pooled. The patients had 2-3 cryotherapy sessions daily for one week plus conventional physiotherapy. Clinical and laboratory variables and patient's and physician's global assessments were used to assess the outcome. Disease activity was calculated by DAS. RESULTS Pain decreased in all treatment groups, most markedly in the whole-body cryotherapy (-110 degrees C) group. DAS decreased slightly with no statistically significant differences between the groups. No serious or permanent adverse effects were detected. Six of 40 patients (15%) discontinued the whole-body cryotherapy. CONCLUSION Pain seemed to decrease more in patients in the whole-body cryotherapy at -110 degrees C than during other cryotherapies, but there were no significant differences in the disease activity between the groups. However, cryotherapy at -110 degrees C is expensive and available only in special centres and may have minor adverse effects. Based on our results, whole-body cryotherapy at -110 degrees C is not superior to local cryotherapy commonly used in RA patients for pain relief and as an adjunct to physiotherapy.
Remodeling of Synaptic AMPA Receptor Subtype Alters the Probability and Pattern of Action Potential Firing

Changes in the subunit composition of postsynaptic AMPA-type glutamate receptors can be induced at CNS synapses by neural activity and under certain pathological conditions. Fear-induced incorporation of GluR2-containing receptors at cerebellar synapses selectively prolongs the decay time of synaptic currents, whereas a switch from GluR2-lacking to GluR2-containing receptors induced by parallel fiber stimulation reduces the amplitude in addition to lengthening the duration of EPSCs. Although it is often assumed that these two forms of synaptic plasticity will alter action potential (AP) firing in the postsynaptic neuron, this has not been directly tested. Using a dynamic current-clamp approach, we now show that the fear-induced increase in EPSC duration increases the size of EPSPs and thereby markedly enhances the AP firing probability. In contrast, the parallel fiber stimulation-triggered switch in GluR2 expression reduces the EPSP–AP coupling because of the decrease in the synaptic current amplitude. The switch also abolished the paired-pulse facilitation that arose from an activity and spermine-dependent unblock of GluR2-lacking receptors and hence reduced the ability of paired stimuli to evoke two consecutive APs. Therefore, fear-induced incorporation of GluR2 receptors enhances the EPSP–AP coupling, but the parallel fiber stimulation-triggered switch reduces both the EPSP–AP coupling and evoked AP doublets. In contrast to long-term potentiation and depression, which modify the amplitude of synaptic currents, this activity-induced change in AMPA receptor phenotype alters synaptic conductance waveform and postsynaptic short-term plasticity. These changes modulate both the probability and pattern of evoked AP firing via a fundamentally different mechanism from long-term potentiation and long-term depression.
Preparatory processes in the task-switching paradigm: evidence from the use of probability cues.

The purpose of the investigations was to dissociate processes of task preparation from task execution in the task-switching paradigm. The basic assumption was that task repetitions have 2 advantages over task shifts: an activation advantage as a result of the execution of the same task type in the pretrial, and an expectation advantage, because participants, in general, implicitly expect a repetition. In Experiments 1-3, the authors explicitly manipulated expectancies by presenting cues that announced a shift and/or a repetition with probabilities of 1.00, . 75, . 50, or . 25. Increasing latencies with decreasing probability for shifts and repetitions show that the expectation advantage can be equalized by preparation. However, the activation advantage represented by constant shift costs between tasks of the same probability is not penetrable by preparation. In Experiments 4 and 5, the authors found evidence that preparation involves activation of the expected task and inhibition of distracting tasks.
Analysis of Tide and Offshore Storm‐Induced Water Table Fluctuations for Structural Characterization of a Coastal Island Aquifer

Analysis of water table fluctuations can provide important insight into the hydraulic properties and structure of a coastal aquifer system including the connectivity between the aquifer and ocean. This study presents an improved approach for characterizing a permeable heterogeneous coastal aquifer system through analysis of the propagation of the tidal signal, as well as offshore storm pulse signals through a coastal aquifer. Offshore storms produce high wave activity, but are not necessarily linked to significant onshore precipitation. In this study, we focused on offshore storm events during which no onshore precipitation occurred. Extensive groundwater level data collected on a sand barrier island (Sable Island, NS, Canada) show nonuniform discontinuous propagation of the tide and offshore storm pulse signals through the aquifer with isolated inland areas showing enhanced response to both oceanic forcing signals. Propagation analysis suggests that isolated inland water table fluctuations may be caused by localized leakage from a confined aquifer that is connected to the ocean offshore but within the wave setup zone. Two‐dimensional groundwater flow simulations were conducted to test the leaky confined‐unconfined aquifer conceptualization and to identify the effect of key parameters on tidal signal propagation in leaky confined‐unconfined coastal aquifers. This study illustrates that analysis of offshore storm signal propagation, in addition to tidal signal propagation, provides a valuable and low resource approach for large‐scale characterization of permeable heterogeneous coastal aquifers. Such an approach is needed for the effective management of coastal environments where water resources are threatened by human activities and the changing climate.
500‐element ultrasound phased array system for noninvasive focal surgery of the brain: A preliminary rabbit study with ex vivo human skulls

The aim of this study was to test a prototype MRI‐compatible focused ultrasound phased array system for trans‐skull brain tissue ablation. Rabbit thigh muscle and brain were sonicated with a prototype, hemispherical 500‐element ultrasound phased array operating at frequencies of 700–800 kHz. An ex vivo human skull sample was placed between the array and the animal tissue. The temperature elevation during 20–30‐sec sonications was monitored using MRI thermometry. The induced focal lesions were observed in T2 and contrast‐enhanced T1‐weighted fast spin echo images. Whole brain histology evaluation was performed after the sonications. The results showed that sharp temperature elevations can be produced both in the thigh muscle and in the brain. High‐power sonications (600–1080 W) produced peak temperatures up to 55°C and focal lesions that were consistent with thermal tissue damage. The lesion size was found to increase with increasing peak temperature. The device was then modified to operate in the orientation that will be used in the clinic and successfully tested in phantom experiments. As a conclusion, this study demonstrates that it is possible to create ultrasound‐induced lesions in vivo through a human skull under MRI guidance with this large‐scale phased array. Magn Reson Med 52:100–107, 2004. © 2004 Wiley‐Liss, Inc.