Miracle-dz/UniFAR-FTUs huggingface dataset:
The Long Road to Automation: Neurocognitive Development of Letter–Speech Sound Processing

In transparent alphabetic languages, the expected standard for complete acquisition of letter–speech sound associations is within one year of reading instruction. The neural mechanisms underlying the acquisition of letter–speech sound associations have, however, hardly been investigated. The present article describes an ERP study with beginner and advanced readers in which the influence of letters on speech sound processing is investigated by comparing the MMN to speech sounds presented in isolation with the MMN to speech sounds accompanied by letters. Furthermore, SOA between letter and speech sound presentation was manipulated in order to investigate the development of the temporal window of integration for letter–speech sound processing. Beginner readers, despite one year of reading instruction, showed no early letter–speech sound integration, that is, no influence of the letter on the evocation of the MMN to the speech sound. Only later in the difference wave, at 650 msec, was an influence of the letter on speech sound processing revealed. Advanced readers, with 4 years of reading instruction, showed early and automatic letter–speech sound processing as revealed by an enhancement of the MMN amplitude, however, at a different temporal window of integration in comparison with experienced adult readers. The present results indicate a transition from mere association in beginner readers to more automatic, but still not “adult-like,” integration in advanced readers. In contrast to general assumptions, the present study provides evidence for an extended development of letter–speech sound integration.
Immunohistochemical analysis of PAI-2 (plasminogen activator inhibitor type 2) and p53 protein in early gastric cancer patients with recurrence: a preliminary report.

BACKGROUND High levels of urokinase-type plasminogen activator (u-PA) were demonstrated in gastric carcinomas along with inhibitors of plasminogen activators (PAI-1 and PAI-2). They may influence the ability to invade and metastasize and therefore be of importance to the risk of recurrence of stomach neoplasms after curative operation. This also appears to be the case for p53 mutations and p53 protein overexpression. METHODS Six patients, all differentiated cancer cases who developed recurrent disease 5-10 years after curative operations for early gastric cancers (recurrence group), were studied in comparison with 49 patients who had no recurrence more than 10 years after similar surgery (control group). The expression of u-PA, PAI-1, PAI-2 and p53 was compared immunohistochemically in the recurrence and control groups. RESULTS The expression of PAI-2 was significantly more frequent in the recurrence group, being found in five (83.3%) patients vs eight (16.3%) in the control group. p53 was expressed in five (83.3%) patients in the recurrence group and in 15 (30.6%) in the control group; the rate was again significantly higher in the former. CONCLUSION The results suggest that PAI-2 and p53 expressed in differentiated early gastric cancers are possible indices of the risk of recurrence.
Effect of varicella zoster virus infection on bone marrow function

Abstract: Background: Most viral infections are known to exert adverse effects on bone marrow function. However, certain viruses have recently been found to be therapeutically beneficial in the treatment of some malignant disorders. Methods and materials: A retrospective study was conducted at the Armed Forces Hospital, Riyadh, Saudi Arabia. The changes in the hematological parameters following varicella‐zoster virus (VZV) infection in patients with a variety of hematological disorders were compared with those in a control group having the same spectrum of disorders and treated in the same unit over the same period of time but never had VZV infection. Both groups of patients received the same treatment protocols for their primary hematological disorders. Definitive treatment (DT) such as chemotherapy alone, anti‐thymocyte globulin or bone marrow transplant was also employed in the management of patients belonging to both groups. Results: White blood cell counts, platelet counts and hemoglobin concentrations in the study group started to increase 40 d after chickenpox or herpes zoster infection and these increases lasted for periods as long as 1050 d. The changes in platelet counts were more pronounced than those in other hematological parameters. There was a significant difference (P < 0.0001) between the two groups of patients in the values of platelet counts achieved between 280 and 1050 d after DT (mean platelet count: 262 × 109/L in the study group vs. 180 × 109/L in the control group, median: 288.17 × 109/L in the study group vs. 180 × 109/L in the control group, range: 102 to 415 × 109/L in the study group vs. 26 to 365 × 109/L in the control group of patients). Compared to the control group, the study group of patients achieved their maximum blood counts much earlier after DT. The maximum leucocytic count was achieved at a mean duration of 269.21 d in the study group and 349.61 d in the control group. The maximum hemoglobin level was achieved at a mean duration of 319.5 d in the study group and 402.6 d in the control group. The maximum platelet count was achieved at a mean duration of 271.4 d in the study group and 318.9 d in the control group of patients. Conclusion: VZV may behave differently from other members of the herpes group of viruses e.g. human cytomegalovirus and Epstein‐Barr virus. Our observations suggest that VZV infection causes stimulation of bone marrow activity.
Bi-specific MHC Heterodimers for Characterization of Cross-reactive T Cells*

T cell cross-reactivity describes the phenomenon whereby a single T cell can recognize two or more different peptide antigens presented in complex with MHC proteins. Cross-reactive T cells have previously been characterized at the population level by cytokine secretion and MHC tetramer staining assays, but single-cell analysis is difficult or impossible using these methods. In this study, we describe development of a novel peptide-MHC heterodimer specific for cross-reactive T cells. MHC-peptide monomers were independently conjugated to hydrazide or aldehyde-containing cross-linkers using thiol-maleimide coupling at cysteine residues introduced into recombinant MHC heavy chain proteins. Hydrazone formation provided bi-specific MHC heterodimers carrying two different peptides. Using this approach we prepared heterodimers of the murine class I MHC protein H-2Kb carrying peptides from lymphocytic choriomeningitis virus and vaccinia virus, and used these to identify cross-reactive CD8+ T cells recognizing both lymphocytic choriomeningitis virus and vaccinia virus antigens. A similar strategy could be used to develop reagents to analyze cross-reactive T cell responses in humans.
Effect of partial outlet obstruction on choline acetyltransferase activity in the rat and rabbit

Partial outlet obstruction of the rabbit bladder induces a rapid and significant increase in bladder mass. This increase in mass is associated with a variety of specific contractile dysfunctions, characterized by a marked decrease in the response to field stimulation (acting through the release of neurogenic transmitters). There is histological evidence indicating that the decrease in the contractile response of isolated strips of rabbit urinary bladder to field stimulation is associated with a degeneration of synaptic membranes within the bladder detrusor (neuropathy). In the current experiments, the effect of partial outlet obstruction in rabbit and rat urinary bladders on choline acetyltransferase activity (ChAT) were determined and correlated with both the level of bladder hypertrophy (increase in mass) and the contractile response to field stimulation. The results can be summarized as follows: In the rabbit, partial outlet obstruction induced a rapid 5‐fold increase in bladder mass over the 7 day period of study. This increase in mass was associated with a decrease in the contractile response of isolated strips of bladder body and base to field stimulation and a decrease in ChAT activity. Interestingly, the rabbit bladder base showed a significantly higher ChAT activity than the bladder body, although the contractile response to muscarinic stimulation was significantly greater in the bladder body than in the base. In the rat, partial outlet obstruction induced a mild 2‐fold increase in bladder mass. No change in ChAT activity was observed in the obstructed bladder. Consistent with this finding, there was no dysfunction in the response to field stimulation in the obstructed rat bladder.
Suicidal ideation and suicide attempts among immigrant adolescents from the former Soviet Union to Israel.

OBJECTIVE A community survey was conducted to examine suicidal ideation and suicide attempts, behavior problems, psychological distress, social support, and adjustment difficulties in a sample of adolescents. METHOD Four hundred six Russian-born Jewish immigrants to Israel, aged 11 to 18 years, were selected to match the age and sex distribution of the total immigrant adolescent population. Two indigenous samples of Jewish adolescents in Russia (n = 203) and in Israel (n = 104) were matched with immigrants for comparison. Parameters of interest were measured with self-administered questionnaires. RESULTS The 6-month prevalence rate of suicidal ideation in the immigrant sample (10.9%) was significantly higher than that for Russian controls (3.5%) but not for Israeli natives (8.7%). There were few gender differences in suicidal ideation and suicide attempts. Older adolescents reported suicidal ideation 2 times more frequently than their younger counterparts. Suicide ideators scored significantly higher than nonideators on all scales of psychological distress and behavior problems. They rated higher sources of immigration difficulties concerning language, physical health, personality characteristics, and family problems but had less socioeconomic and intercultural problems of migration and lower social support from the family but not from other sources. CONCLUSIONS Results clearly support the migration-convergence hypothesis of suicide risk among adolescents.
Inhibition of axonal growth from sensory neurons by excess nerve growth factor

Fifteen‐day embryonic rat dorsal root ganglion (DRG) neurons were exposed to 1 to 200 ng/ml nerve growth factor (NFG). Maximal neurite outgrowth was obtained with 10 to 20 ng/ml. Neurite outgrowth was reduced to 89% of maximal by increasing NGF to 50 ng/ml, to 66% by 100 ng/ml, and to 18% by 200 ng/ml NGF. Identical effects were seen with mouse 2.5S NGF and recombinant human NGF. Neuron cell counts demonstrated that significant cell death did not occur. In time course experiments, significant inhibition, compared with control, began within 1 hour of adding 200 ng/ml and 3 hours of adding 50 ng/ml NGF. The inhibitory effect of NGF on neurite outgrowth was reversed within 3 hours when DRG were incubated with 5 ng/ml NGF after treatment with 50 or 200 ng/ml NGF medium for 12 hours. The inhibition demonstrated for neurons did not occur in PC12 cells; axonal growth was not inhibited by up to 1,000 ng/ml NGF. Excess brain‐derived neurotrophic factor or neurotrophin‐3 did not inhibit neurite outgrowth. We conclude that high concentrations of NGF produces specific and reversible arrest of neurite outgrowth from sensory neurons. This observation has important clinical implications, because these inhibitory concentrations have been exceeded when NGF has been administered into the central nervous system of humans and animals.
Neuroprotective efficacy of caramiphen against soman and mechanisms of its action

BACKGROUND AND PURPOSE Caramiphen is a muscarinic antagonist with potent anticonvulsant properties. Here, we investigated the efficacy of caramiphen against behavioural seizures and neuropathology induced by the nerve agent soman, and revealed two mechanisms that may underlie the anticonvulsant efficacy of caramiphen.
Nitric oxide‐cGMP pathway facilitates acetylcholine release and bradycardia during vagal nerve stimulation in the guinea‐pig in vitro

1 We tested the hypothesis that nitric oxide (NO) augments vagal neurotransmission and bradycardia via phosphorylation of presynaptic calcium channels to increase vesicular release of acetylcholine. 2 The effects of enzyme inhibitors and calcium channel blockers on the actions of the NO donor sodium nitroprusside (SNP) were evaluated in isolated guinea‐pig atrial‐right vagal nerve preparations. 3 SNP (10 μm) augmented the heart rate response to vagal nerve stimulation but not to the acetylcholine analogue carbamylcholine (100 nm). SNP also increased the release of [3H]acetylcholine in response to field stimulation. No effect of SNP was observed on either the release of [3H] acetylcholine or the HR response to vagal nerve stimulation in the presence of the guanylyl cyclase inhibitor 1H‐(1,2,4)‐oxadiazolo‐(4,3‐a)‐quinoxalin‐1‐one (ODQ, 10 μm). 4 The phosphodiesterase 3 (PDE 3) inhibitor milrinone (1 μm) increased the release of [3H] acetylcholine and the vagal bradycardia and prevented any further increase by SNP. SNP was still able to augment the vagal bradycardia in the presence of the protein kinase G inhibitor KT5823 (1 μm) but not after protein kinase A (PKA) inhibition with H‐89 (0.5 μm) or KT5720 (1 μm) had reduced the HR response to vagal nerve stimulation. Neither milrinone nor H‐89 changed the HR response to carbamylcholine. 5 SNP had no effect on the magnitude of the vagal bradycardia after inhibition of N‐type calcium channels with ω‐conotoxin GVIA (100 nm). 6 These results suggests that NO acts presynaptically to facilitate vagal neurotransmission via a cGMP‐PDE 3‐dependent pathway leading to an increase in cAMP‐PKA‐dependent phosphorylation of presynaptic N‐type calcium channels. This pathway may augment the HR response to vagal nerve stimulation by increasing presynaptic calcium influx and vesicular release of acetylcholine.
Quality and Quantity of Saliva DNA Obtained from the Self-administrated Oragene Method—A Pilot Study on the Cohort of Swedish Men

Self-collection of saliva has the potential to provide molecular epidemiologic studies with DNA in a user-friendly way. We evaluated the new Oragene saliva collection method and requested saliva samples by mail from 611 men (ages 53-87 years). We obtained a response rate of, on average, 80% [varying from 89% (ages 67-71 years) to 71% (ages 77-87 years)]. DNA was extracted from 90 randomly selected samples, and its usefulness was evaluated with respect to quality, quantity, and whole-genome amplification (WGA). Visual inspection of DNA on agarose gels showed high molecular weight DNA (>23 kb) and no degradation. Total DNA yield measured with PicoGreen ranged from 1.2 to 169.7 μg, with a mean of 40.3 μg (SD, 36.5 μg) and a median of 29.4 μg. Human DNA yield was estimated by real-time PCR of the human prothrombin gene to account for 68% (SD, 20%) of total DNA. We did WGA on 81 saliva DNA samples by using the GenomiPhi DNA kit and genotyped both saliva DNA and WGA DNA for 10 single-nucleotide polymorphisms randomly selected from the human genome. Overall genotyping success rate was 96% for saliva DNA and 95% for WGA DNA; 79% of saliva DNA samples and 79% of WGA DNA samples were successfully genotyped for all 10 single-nucleotide polymorphisms. For the 10 specific assays, the success rates ranged between 88% and 100%. Almost complete genotypic concordance (99.7%) was observed between saliva DNA and WGA DNA. In conclusion, Oragene saliva DNA in this study collected from men is of high quality and can be used as an alternative to blood DNA in molecular epidemiologic studies. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1742–5)
Adenosine A2A-Dopamine D2 Receptor-Receptor Heteromerization

There is evidence for strong functional antagonistic interactions between adenosine A2A receptors (A2ARs) and dopamine D2 receptors (D2Rs). Although a close physical interaction between both receptors has recently been shown using co-immunoprecipitation and co-localization assays, the existence of a A2AR-D2R protein-protein interaction still had to be demonstrated in intact living cells. In the present work, fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) techniques were used to confirm the occurrence of A2AR-D2R interactions in co-transfected cells. The degree of A2AR-D2R heteromerization, measured by BRET, did not vary after receptor activation with selective agonists, alone or in combination. BRET competition experiments were performed using a chimeric D2R-D1R in which helices 5 and 6, the third intracellular loop (I3), and the third extracellular loop (E3) of the D2R were replaced by those of the dopamine D1 receptor (D1R). Although the wild type D2R was able to decrease the BRET signal, the chimera failed to achieve any effect. This suggests that the helix 5-I3-helix 6-E3 portion of D2R holds the site(s) for interaction with A2AR. Modeling of A2AR and D2R using a modified rhodopsin template followed by molecular dynamics and docking simulations gave essentially two different possible modes of interaction between D2R and A2AR. In the most probable one, helix 5 and/or helix 6 and the N-terminal portion of I3 from D2R approached helix 4 and the C-terminal portion of the C-tail from the A2AR, respectively.
Nitric oxide synthase inhibition affects sarcoplasmic reticulum Ca2+ release in skeletal muscle fibres from mouse

Nitric oxide (NO) generated by skeletal muscle is believed to regulate force production but how this is achieved remains poorly understood. In the present work we tested the effects of NO synthase (NOs) inhibitors on membrane current and intracellular calcium in isolated skeletal muscle fibres from mouse, under voltage‐clamp conditions. Resting [Ca2+] and [Ca2+] transients evoked by large depolarizations exhibited similar properties in control fibres and in fibres loaded with tenth millimolar levels of the NOs inhibitor N‐nitro‐l‐arginine (l‐NNA). Yet the voltage dependence of calcium release was found to be shifted by ∼15 mV towards negative values in the presence of l‐NNA. This effect could be reproduced by the other NOs inhibitor S‐methyl‐l‐thiocitrulline (l‐SMT). Separate experiments showed that the voltage dependence of charge movement and of the slow calcium current were unaffected by the presence of l‐NNA, ruling out an effect on the voltage sensor. A negative shift in the voltage dependence of calcium release with no concurrent alteration in the properties of charge movement was also observed in fibres exposed to the oxidant H2O2 (1 mm). Conversely the reducing agent dithiothreitol (10 mm) had no obvious effect on Ca2+ release. Overall, the results indicate that physiological levels of NO exert a tonic inhibitory control on the activation of the calcium release channels. Changes in the voltage dependence of Ca2+ release activation may be a ubiquitous physiological consequence of redox‐related modifications of the ryanodine receptor.
The uncertainty effect on saving decisions: An empirical analysis for the spanish economy

espanolEsta tesis analiza si hay un efecto de la incertidumbre sobre las decisiones de consumo y ahorro de las familias espanolas, generando ahorro por motivo precaucion. Las cuestiones relacionadas con la toma de decisiones en contextos de incertidumbre han cobrado especial relevancia en los ultimos anos, en los que la agitacion financiera, economica y politica provoco un aumento de la incertidumbre sobre la renta futura de los hogares. Aunque la hipotesis de ahorro precaucion ha sido contrastada en un gran numero de trabajos, tanto a nivel macroeconomico como microeconomico, los resultados empiricos no son concluyentes. No se ha llegado a un consenso sobre la intensidad de ese motivo para el ahorro, ni sobre cual es la medida de incertidumbre mas adecuada. La tesis ofrece, en el primer capitulo, una revision de la literatura que ha abordado empiricamente la existencia de ahorro precaucion. La conclusion general que se extrae de dicha revision es que la incertidumbre afecta a las decisiones de consumo y ahorro, aunque no todas las medidas que se pueden utilizar para aproximar la incertidumbre son adecuadas para todos los paises o en todos los contextos macroeconomicos. Este es tambien el resultado alcanzado en los analisis que realizamos para el caso de Espana. En la tesis se evalua, en los capitulos dos y tres, el efecto de la incertidumbre sobre las decisiones de consumo/ahorro de los hogares espanoles, a traves de analisis empiricos con datos de la Encuesta Financiera de las Familias. Por una parte, usando datos de corte transversal, construimos diversas medidas de incertidumbre, empleadas habitualmente en la literatura, asi como un indicador adicional basado en datos de precariedad laboral. Por otra parte, explotando el componente de panel de la encuesta, construimos una medida de variabilidad de la renta, que es la proxy de incertidumbre mas comunmente utilizada en los trabajos empiricos. En ambos analisis obtenemos evidencia a favor de la hipotesis del ahorro precaucion. EnglishUncertainty plays a significant role on consumption and saving decisions under rather mild conditions, namely the convexity of the marginal utility of consumption. Increased uncertainty generates a positive extra saving, the “precautionary saving”. Although this hypothesis has been tested by a large number of authors, both at macro and micro level, the empirical results are not conclusive, and the main conclusion than can be drawn is that there is neither consensus on the intensity of that motive for saving, nor on the most appropriate measure of uncertainty. This thesis test the effect of the uncertainty on consumption/saving decisions of Spanish households through an empirical analysis with data from the Survey of Households Finances.
Financial Development and Output Volatility: A Cross-Sectional Panel Data Analysis

This paper aims to provide a more comprehensive understanding of the impact of financial developments on output volatility. Using cross-sectional and panel datasets for 79 countries from 1961 to 2012, we find that financial expansion plays a significant role in mitigating output volatility, although the evidence is weak in some cases. The role of financial stability is more prominent than that of other measures of financial growth in mitigating output volatility. The volatility of terms of trade and inflation contributes positively to increasing output volatility. We also evaluate the channels through which financial developments can affect output volatility. Our model investigates the link between financial growth and output volatility through two potential channels, using four measures of financial development. The volatility of inflation and of terms of trade are used as proxies for monetary sector and real sector volatility, respectively. Financial development plays a mixed role in amplifying or mitigating output volatility through real and monetary sector volatility. Overall, there is some evidence to suggest that financial development amplifies monetary sector volatility, but weaker evidence that real sector volatility is reduced by financial development.