Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantification of Feline Herpesvirus 1 DNA in Ocular Fluid Samples of Clinically Diseased Cats by Real-Time TaqMan PCR

ABSTRACT A fluorogenic PCR was established for the quantification of feline herpesvirus 1 (FeHV-1) DNA in ocular fluid samples of clinically diseased cats. The new assay was specific for FeHV-1 and sensitive. The 100% detection rate ranged from 0.6 to 6 50% tissue culture infective doses per sample. When spiked samples with known quantities of virus were used, infectious virus titers and quantification of viral DNA by PCR correlated to each other in a linear fashion (R2 = 0.9858) over a range of 4 orders of magnitude. Within this range, it was possible to calculate the FeHV-1 DNA content from a given infectious dose, and vice versa. The new diagnostic procedure was applied to ocular fluid samples from cats experimentally infected with FeHV-1 and specific FeHV-1-free cats. A good correlation between virus titer and quantitative PCR was observed, although only early in infection. In a second stage, the titer of infectious virus collapsed, while the PCR signal remained high. A constantly decreasing PCR signal accompanied by negative virus isolation was characteristic for a final stage of the infection. Finally, clinical samples from 20 cats that were suspected to suffer from FeHV-1 infection were analyzed. By comparing virus titers and quantitative PCR signals, it was possible to determine the current stage of the ongoing infection. Based on these findings, comparison of the results of consecutive samples allows the tracking of the course of the infection. Therefore, the new method combines the advantages of the two previously established conventional methods, qualitative PCR and virus isolation and titration.
Tuberculin responses in children with allergic diseases

Background: The prevalence of allergic disorders has been increasing over the last 30 years, especially in developed countries. One factor associated with this rise may be the decline of many childhood infections. We investigated tuberculin responses in allergic children in order to see the development of delayed‐type hypersensitivity reactions to tubercule bacillus infection.
Exaggerated IDO1 expression and activity in Langerhans cells from patients with atopic dermatitis upon viral stimulation: a potential predictive biomarker for high risk of Eczema herpeticum

Atopic dermatitis (AD) is a heterogenous and highly complex disease characterized by an increased microbial colonization. For unknown reasons, a subgroup of patients with AD develops Eczema herpeticum (EH), a severe viral complication due to spreading of herpes simplex virus (HSV). Indoleamine 2,3‐dioxygenase (IDO1) is a tryptophan (Trp)‐catabolizing enzyme which is assumed to be instrumental in the antibacterial and antiviral defence mechanisms.
Anti-Immunoglobulin E Treatment of Patients with Recalcitrant Physical Urticaria

In physical urticaria, exogenous physical factors such as thermal triggers, solar radiation and mechanic triggers including friction or pressure are responsible for the elicitation of symptoms in the skin of patients. Avoidance of the respective stimulus is usually difficult or impossible, and many patients are not sufficiently treated with standard antihistamines. We report that treatment with omalizumab (Xolair®) of 7 patients with physical urticarias [solar urticaria (n = 2), urticaria factitia/symptomatic dermographism (n = 2), cold urticaria, delayed pressure urticaria and localized heat urticaria] resulted in complete symptom control within days after the first injection in 5 patients. In 1 patient, symptoms improved after increasing the dose of omalizumab, and 1 patient with localized heat urticaria did not respond significantly to treatment. Before anti-immunoglobulin E treatment, all patients had suffered from their physical urticaria for years and had had numerous unsuccessful therapies. The overall excellent responses to omalizumab treatment reported here indicate that anti-immunoglobulin E is a safe and effective treatment for recalcitrant physical urticarias.
Preconditioning with tin-protoporphyrin IX attenuates ischemia/reperfusion injury in the rat kidney.

BACKGROUND Heme oxygenase (HO)-1 is induced as a unique stress response and leads to a transient resistance against oxidative damage, including ischemia and reperfusion (I/R) injury. In the present study, we examined whether HO-1 induction may confer a protection against I/R injury in the rat kidney. METHODS Lewis rats were divided into four groups as follows: (1) vehicle group; (2) group treated with ferri-protoporphyrin IX (hemin), an inducer of HO; (3) group treated with low-dose tin-protoporphyrin IX (SnPP), an inhibitor of HO; and (4) group treated with high-dose SnPP. Renal warm ischemia for 60 minutes was performed 24 hours after each treatment. RESULTS At 24 hours after treatment, hemin induced a significant increase in renal HO activity, but failed to induce HO-1 protein synthesis. Although both low- and high-dose SnPP reduced HO activity, a marked HO-1 expression was observed only in the high-dose SnPP-treated kidney. Hemin exacerbated the renal function after reperfusion, while high-dose SnPP significantly suppressed the intercellular adhesion molecule (ICAM)-1 expression, the infiltration of ED-1-positive macrophages and the expression of activated caspase-3, which resulted in attenuation of apoptotic cell death and ameliorated I/R injury. CONCLUSION These results suggest that prior induction of HO-1 protein by high-dose SnPP may lead to anti-inflammatory and antiapoptotic effects on warm renal I/R injury independently of its enzyme activity, and that HO enzyme activation may not always act as an antioxidant, especially under I/R-induced oxidative stress.
Architectural properties of the first dorsal interosseous muscle

Muscle architecture is considered to reflect the function of muscle in vivo, and is important for example to clinicians in designing tendon‐transfer and tendon‐lengthening surgeries. The purpose of this study was to quantify the architectural properties of the FDI muscle. It is hypothesized that there will be consistency, that is low variability, in the architectural parameters used to describe the first dorsal interosseous muscle because of its clear functional role in index finger motion. The important architectural parameters identified were those required to characterize a muscle adequately by modeling. Specifically the mass, cross‐sectional area, and length of the tendon and muscle were measured in cadavers along with the muscle fiber optimum length and pennation angle, and the moment arm of the first dorsal interosseous at the metacarpophalangeal joint. These parameters provide a characterization of the architecture of the first dorsal interosseous, and were used to indicate the inherent variability between samples. The results demonstrated a large amount of variability for all architectural parameters measured; leading to a rejection of the hypothesis. Ratios designed to describe the functioning of the muscles in vivo, for example the ratio of tendon to fiber optimum lengths, also demonstrated a large variability. The results suggest that function cannot be deduced from form for the first dorsal interosseous, and that subject‐specific architectural parameters may be necessary for the formulation of accurate musculoskeletal models or making clinical decisions.
Money and Capital

Like many other historians and economists before him, Thomas Piketty includes money in his definition of capital (wealth). This obliges him to distinguish between real and nominal assets, notably to understand the distributional effect of inflation on capital. This article draws comparisons between this approach and other theories of the difference between money and capital, before going on to show, from a historical point of view, why the role and the share of money within total capital cannot be neglected. Potential substitution effects between monetary and non-monetary assets must to be taken into account in order to understand the historical dynamic of capital and the effects of its taxation.
An International Sensitivity Index (ISI) derived from patients with abnormal liver function improves agreement between INRs determined with different reagents

Summary The International Normalised Ratio (INR)/International Sensitivity Index (ISI) system was developed as a way to standardise the prothrombin time during the monitoring of patients undergoing oral anti-coagulant therapy with vitamin K antagonists. The wide acceptance of the INR has led to its use as one of three parameters used in the Model for End stage Liver disease (MELD) scoring system to aid the prioritisation of patients for liver transplant. Literature published recently has highlighted the potential inadequacy of the INR system in this context. Our aim was to investigate the degree of difference between INR values calculated using an ISI derived from warfarinised patients and those calculated using an ISI derived from patients with liver disease. Prothrombin times from 60 patients with liver disease were determined using three working thromboplastin reagents; Innovin®, Thromborel S® and Thromboplastin C® and two reference thromboplastins; rTF/95 and RBT/05. All thromboplastin reagents tested had standard international sensitivity indices (ISIs) assigned following calibration with patients on oral anticoagulant therapy (ISIvka). As a result of the new calibration each of the working thromboplastin reagents was assigned a specific “liver patient” ISI. Two INR values were calculated for each thromboplastin patient involved in the calibration. A comparison of the mean INRliver with INRvka showed a statistically significant difference between the two values (p<0.0001). A similar relationship existed for INRs on a further 20 patients with liver disease whose plasmas were not used to derive the ISIliver. This difference led to a change in the final MELD score and could therefore affect the prioritisation and management of these patients.
Cardiovascular reactivity to and recovery from stressful tasks following a mindfulness analog in college students with a family history of hypertension.

OBJECTIVES Ninety-seven (97) undergraduates with a family history of hypertension participated in a study that evaluated the effects of a brief mindfulness-induction on cardiovascular reactivity and recovery to two stressors. MATERIALS AND METHODS Participants were randomized to either a mindfulness-induction or control condition and were then exposed to the cold pressor task (CPT) followed by the mirror-tracing task (MT). Blood pressure and heart rate were measured at baseline and postinduction, as well as during and immediately following each stressor. RESULTS There were no group differences in reactivity to either stressor. Participants in the mindfulness-analog condition experienced significantly greater latency to systolic blood pressure recovery following the CPT and a tendency toward greater latency to diastolic blood pressure recovery, although these findings were not replicated with the MT task. CONCLUSIONS These results are contrary to what was hypothesized and to the anecdotal evidence available regarding effects of comprehensive mindfulness interventions on reactivity. The findings are discussed with respect to purported mechanisms of mindfulness and learning theory.
Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration

ABSTRACT Recent work suggested that the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related macular degeneration (ARMD) patients and therefore could be an attractive therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer therapy, with severe and noncharacterized ocular side effects. To decipher the role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration. Our results identify the ERK1/2 pathway as a direct regulator of the visual cycle and a critical component of the viability of RPE and photoreceptor cells. Moreover, our results caution about the need for a very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to avoid ocular side effects.
DNA glycosylases search for and remove oxidized DNA bases

This review article presents, an overview of the DNA glycosylases that recognize oxidized DNA bases using the Fpg/Nei family of DNA glycosylases as models for how structure can inform function. For example, even though human NEIL1 and the plant and fungal orthologs lack the zinc finger shown to be required for binding, DNA crystal structures revealed a “zincless finger” with the same properties. Moreover, the “lesion recognition loop” is not involved in lesion recognition, rather, it stabilizes 8‐oxoG in the active site pocket. Unlike the other Fpg/Nei family members, Neil3 lacks two of the three void‐filling residues that stabilize the DNA duplex and interact with the opposite strand to the damage which may account for its preference for lesions in single‐stranded DNA. Also single‐molecule approaches show that DNA glycosylases search for their substrates in a sea of undamaged DNA by using a wedge residue that is inserted into the DNA helix to probe for the presence of damage. Environ. Mol. Mutagen. 54:691–704, 2013. © 2013 Wiley Periodicals, Inc.
Asymmetry Effects of Exchange Rate Changes on Domestic Production in Emerging Countries

ABSTRACT Previous studies that tried to assess the impact of exchange rate changes on domestic production of emerging economies assumed that the effects are symmetric and used a linear model to provide mixed results. In this article, we try to determine whether exchange rate changes could have asymmetric effects which amounts to using a nonlinear model. We find that the nonlinear model performs much better than the linear model and yields results that support asymmetry effects of exchange rate changes on domestic production in many of the countries in our sample, both in the short run and in the long run.
Reactive Oxygen Species Released from Mitochondria during Brief Hypoxia Induce Preconditioning in Cardiomyocytes*

Reactive oxygen species (ROS) have been proposed to participate in the induction of cardiac preconditioning. However, their source and mechanism of induction are unclear. We tested whether brief hypoxia induces preconditioning by augmenting mitochondrial generation of ROS in chick cardiomyocytes. Cells were preconditioned with 10 min of hypoxia, followed by 1 h of simulated ischemia and 3 h of reperfusion. Preconditioning decreased cell death from 47 ± 3% to 14 ± 2%. Return of contraction was observed in 3/3 preconditioned versus 0/6 non-preconditioned experiments. During induction, ROS oxidation of the probe dichlorofluorescin (sensitive to H2O2) increased ∼2.5-fold. As a substitute for hypoxia, the addition of H2O2 (15 μmol/liter) during normoxia also induced preconditioning-like protection. Conversely, the ROS signal during hypoxia was attenuated with the thiol reductant 2-mercaptopropionyl glycine, the cytosolic Cu,Zn-superoxide dismutase inhibitor diethyldithiocarbamic acid, and the anion channel inhibitor 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, all of which also abrogated protection. ROS generation during hypoxia was attenuated by myxothiazol, but not by diphenyleneiodonium or the nitric-oxide synthase inhibitor l-nitroarginine. We conclude that hypoxia increases mitochondrial superoxide generation which initiates preconditioning protection. Furthermore, mitochondrial anion channels and cytosolic dismutation to H2O2 may be important steps for oxidant induction of hypoxic preconditioning.
In vivo quantification of neuro‐glial metabolism and glial glutamate concentration using 1H‐[13C] MRS at 14.1T

Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo 13C NMR spectroscopy coupled with the infusion labeled glial‐specific substrate, such as acetate. In this study, we infused alpha‐chloralose anesthetized rats with [2‐13C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using 1H‐[13C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two‐compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid (TCA) cycle rate (Vg) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (VNT) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR. Pyruvate carboxylase (VPC) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (Vxg and Vxn) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations.
An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans

Objective Carotid–femoral pulse wave velocity (PWV) has been shown to be a powerful predictor of cardiovascular morbidity and mortality. Sympathetic neural mechanisms may have a stiffening influence on arterial mechanical properties. The relationship between direct measures of sympathetic traffic and PWV in healthy humans has not been previously studied. We, therefore, tested the hypothesis that PWV is independently linked to muscle sympathetic nerve activity (MSNA) in normal individuals. Methods We measured MSNA (microneurography), PWV (Complior device), heart rate and blood pressure in 25 healthy male participants (mean age 43 ± 10 years). Results PWV correlated significantly with age (r = 0.63, P < 0.001), SBP (r = 0.43, P < 0.05) and MSNA (r = 0.43, P < 0.05) but not with BMI, waist circumference, waist-to-hip ratio, heart rate, pulse pressure or DBP. Robust multiple linear regression analysis revealed that only age and MSNA were linked independently to PWV (r2 = 0.62, P < 0.001), explaining 39 and 25% of its variance, respectively. After adjustment of PWV for age and SBP, we further divided individuals into ‘excessive’ PWV (i.e. higher than expected from age and SBP) and ‘optimal’ PWV (i.e. lower than expected). BMI and blood pressure were similar in both subgroups. Individuals with excessive PWV had significantly greater MSNA than individuals with optimal PWV (30 ± 10 vs. 18 ± 11 bursts/min, P = 0.01). Conclusion This study provides the first evidence that PWV is linked to MSNA in normal humans. The relationship between MSNA and PWV is independent of age, BMI, waist circumference, waist-to-hip ratio, heart rate, pulse pressure or blood pressure.
Expected clinical benefits of paliperidone extended-release formulation when compared with risperidone immediate-release

Background: The development of paliperidone extended release (ER) may represent a new strategy to improve the pharmacological treatment of schizophrenia. The drug maintains the atypical antipsychotic profile of its parent compound risperidone, but it is associated with an innovative delivery system (OROS technology) that offers the possibility to obtain smooth drug plasma levels using an oral antipsychotic. Clinical trials confirmed that paliperidone ER is efficacious in the management of schizophrenia and well tolerated, however no direct clinical comparisons between paliperidone ER and immediate-release formulations of risperidone have been conducted to date. Objective: The present study evaluates possible differences between paliperidone ER and immediate-release formulations of risperidone due to structural/molecular and delivery system diversities, providing an estimation of their significance in the context of clinical results. Methods: A search of Medline and EMBASE was performed using the keywords ‘Risperidone’, ‘Paliperidone’ and ‘OROS technology’. Results/conclusion: The analysis suggests that the chemical structure and pharmacokinetic profile of paliperidone ER might provide clinical benefits in terms of efficacy, tolerability and more consistent drug response among patients, when compared with the parent compound risperidone in its immediate release formulations. The relevance of these differences is discussed, taking into account several clinical aspects involved in the drug therapy of schizophrenia.
19 User Experience in Digital Games

This chapter concentrates on the psychological analysis of the user experience (UX). We present three different psychological frameworks that have been used in the study of complex UX environments. They have been widely applied in different game contexts studied by the PDL (Psychology of Digital Life) research group at the University of Helsinki. The frameworks work their way from very general and theoretical aspects towards more specific and empirically validated model of the UX in games. Both theoretical and methodological issues are presented, including the empirical data collected (n=2200) and the directional results that demonstrate how the psychological UX framework works in practice. Some other technology environments are also considered within the fundamental psychological concepts that all these frameworks share, that is, cognitions, emotions and motivations. It is shown, how basic psychology can be applied in order to understand the rich variety of human experiences. There are profound reasons to study games. They provide interactive entertainment for millions of users around the world. Economically they have exceeded traditional media, such as movies and music. Game companies have become forerunners of the software industry, guiding the future of the whole field and having impact also on hardware development. Gaming technology will be applied in numerous other areas as socially interactive virtual worlds (e.g., 2nd Life) have already shown. New generations familiar with being and interacting in virtual environments are born. The daily activities of these citizens are shifting towards the world wide virtual world. This change has made games and virtual worlds also true topics in cultural discussions. Since games are played to get experiences, they are hard to study and understand with traditional usability methods that are typically applied in the field of human-computer interaction (HCI). This will be problematic when the future user interfaces evolve towards those used in games today. Thus, more holistic approaches to understand and evaluate the inner worlds of the users and their complex functionality in numerous technological contexts are required. When the holistic nature of the human experience is studied systematically with methodologically solid approaches, psychological understanding of the human experience in such environments increases and benefits the designing of value and UX for these environments.