Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning-induced neural plasticity of speech processing before birth

Significance Learning, the foundation of adaptive and intelligent behavior, is based on changes in neural assemblies and reflected by the modulation of electric brain responses. In infancy, long-term memory traces are formed by auditory learning, improving discrimination skills, in particular those relevant for speech perception and understanding. Here we show direct neural evidence that neural memory traces are formed by auditory learning prior to birth. Our findings indicate that prenatal experiences have a remarkable influence on the brain’s auditory discrimination accuracy, which may support, for example, language acquisition during infancy. Consequently, our results also imply that it might be possible to support early auditory development and potentially compensate for difficulties of genetic nature, such as language impairment or dyslexia. Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.
The Effect of Completing the Beck Depression Inventory on Self-Reported Mood State: Contrast and Assimilation

It was hypothesized that completion of the Beck Depression Inventory (BDI) would influence self-reported mood, through subjects' comparison of their own state with the affectively negative content of the BDI. In Study 1, college students completed the BDI, Snyder's Self-Monitoring scale, or no initial questionnaire before completing a 20-item mood measure. Given the generally positive affective state and self-relevant constructs of college students, it was expected that subjects completing the BDI would contrast their own state with its affectively dissimilar content and would derive from the BDI a (negative) standard of reference against which they would evaluate their current state; consequently, it was hypothesized that completion of the BDI would result in a more positive mood. As predicted, subjects who had completed the BDI reported the most positive affect. In Study 2, subjects were dichotomized on depression scores and completed the BDI either before or after a mood measure. It was expected that, among subjects who completed the BDI first, nondepressed subjects would contrast the BDI content and report more positive moods, but depressed subjects would assimilate the BDI content and report more negative moods. Overall, subjects reported more positive mood after completing the BDI. However; this effect was attenuated for the depressed group. In Study 3 a more depressed group was employed, and the predicted interaction was observed. That is, depressed subjects were more negative, and nondepressed subjects more positive, if they first completed the BDL. The results are discussed in terms of the implications for future research and the interpretation of past research.
Mycolic Acid Modification by the mmaA4 Gene of M. tuberculosis Modulates IL-12 Production

Mycobacterium tuberculosis has evolved many strategies to evade elimination by the host immune system, including the selective repression of macrophage IL-12p40 production. To identify the M. tuberculosis genes responsible for this aspect of immune evasion, we used a macrophage cell line expressing a reporter for IL-12p40 transcription to screen a transposon library of M. tuberculosis for mutants that lacked this function. This approach led to the identification of the mmaA4 gene, which encodes a methyl transferase required for introducing the distal oxygen-containing modifications of mycolic acids, as a key locus involved in the repression of IL-12p40. Mutants in which mmaA4 (hma) was inactivated stimulated macrophages to produce significantly more IL-12p40 and TNF-α than wild-type M. tuberculosis and were attenuated for virulence. This attenuation was not seen in IL-12p40-deficient mice, consistent with a direct linkage between enhanced stimulation of IL-12p40 by the mutant and its reduced virulence. Treatment of macrophages with trehalose dimycolate (TDM) purified from the ΔmmaA4 mutant stimulated increased IL-12p40, similar to the increase observed from ΔmmaA4 mutant-infected macrophages. In contrast, purified TDM isolated from wild-type M. tuberculosis inhibited production of IL-12p40 by macrophages. These findings strongly suggest that M. tuberculosis has evolved mmaA4-derived mycolic acids, including those incorporated into TDM to manipulate IL-12-mediated immunity and virulence.
The sound of your lips: electrophysiological cross-modal interactions during hand-to-face and face-to-face speech perception

Recent magneto-encephalographic and electro-encephalographic studies provide evidence for cross-modal integration during audio-visual and audio-haptic speech perception, with speech gestures viewed or felt from manual tactile contact with the speaker’s face. Given the temporal precedence of the haptic and visual signals on the acoustic signal in these studies, the observed modulation of N1/P2 auditory evoked responses during bimodal compared to unimodal speech perception suggest that relevant and predictive visual and haptic cues may facilitate auditory speech processing. To further investigate this hypothesis, auditory evoked potentials were here compared during auditory-only, audio-visual and audio-haptic speech perception in live dyadic interactions between a listener and a speaker. In line with previous studies, auditory evoked potentials were attenuated and speeded up during both audio-haptic and audio-visual compared to auditory speech perception. Importantly, the observed latency and amplitude reduction did not significantly depend on the degree of visual and haptic recognition of the speech targets. Altogether, these results further demonstrate cross-modal interactions between the auditory, visual and haptic speech signals. Although they do not contradict the hypothesis that visual and haptic sensory inputs convey predictive information with respect to the incoming auditory speech input, these results suggest that, at least in live conversational interactions, systematic conclusions on sensory predictability in bimodal speech integration have to be taken with caution, with the extraction of predictive cues likely depending on the variability of the speech stimuli.
Interaction between Gonadal Steroids and Neuroimmune System in Acute Experimental Autoimmune Encephalomyelitis (EAE) in Wistar Rats

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the CNS mediated by autoreactive T lymphocytes directed against myelin antigens. Since neuroendocrine-immune dysfunction appears to contribute to the pathogenesis of autoimmune diseases, the present work was designed to study the effect of changes in the endocrine system on the development of acute EAE and the immune response against myelin basic protein (MBP). Intact and sham males and intact female Wistar rats showed the most severe clinical symptoms (acute period) 12–14 days post-inoculation (dpi). Then, they began gradually to recover, regaining the total ability to walk by 15–17 dpi. Male Wistar rats with altered levels of gonadal hormones by surgical castration showed an onset of the symptoms retarded 2–3 days with respect to the other EAE groups, showing neuropathological symptoms up to 27–28 dpi, and remaining with lower body weight even at 40 dpi. The castrated animals exhibited a specific delay in MBP-stimulated DTH reactivity that correlates with the delay in the onset of the clinical symptoms. Also significant lymphocyte proliferation to MBP was still present at 35 dpi that was absent in the sham group. The distribution of the IgG subclasses indicated that at 35 dpi castrated animals have a higher IgG2b/IgG1 ratio (35.1) in comparison to that presented by sham rats (4.8). Considering that at this time the castrated animals were not completely recuperated, these results could indicate an ongoing inflammatory immune response associated with Th1 activity in these animals. Also castrated animals developed antibodies to a diversity of MBP epitopes in comparison to sham rats, which presented a dominance of antibodies to MBP peptide p96–128. These results indicate that sex hormones levels regulate cell-mediated immunity and the specificity of anti-MBP antibodies related to the induction and development of acute EAE.
Influence of treatment with alendronate on the speed of sound, an ultrasound parameter, of the calcaneus in postmenopausal Japanese women with osteoporosis: a clinical practice-based observational study

Purpose The influence of alendronate (ALN) treatment on the quantitative ultrasound parameters of the calcaneus remains to be established in Japanese patients. The aim of the present clinical practice-based observational study was to examine the influence of ALN treatment for 1 year on the speed of sound (SOS) of the calcaneus and bone turnover markers in postmenopausal Japanese women with osteoporosis. Patients and methods Forty-five postmenopausal Japanese women with osteoporosis who had received treatment with ALN for more than 1 year were enrolled in the study. The SOS and bone turnover markers were monitored over 1 year of ALN treatment. Results The urinary levels of cross-linked N-terminal telopeptides of type I collagen and serum levels of alkaline phosphatase decreased significantly from the baseline values (−44.9% at 3 months and −22.2% at 12 months, respectively). The SOS increased modestly, but significantly, from the baseline value (0.6% at both 6 and 12 months). The percentage decrease in the urinary levels of cross-linked N-terminal telopeptides of type I collagen at 3 months was significantly correlated with the percentage increase in the SOS only at 6 months (correlation coefficient, 0.299). Conclusion The present study confirmed that ALN treatment suppressed bone turnover, producing a clinically significant increase in the SOS of the calcaneus in postmenopausal Japanese women with osteoporosis.
β-TCP granules mixed with reticulated hyaluronic acid induce an increase in bone apposition

β beta-tricalcium phosphate (β-TCP) granules are suitable for repair of bone defects. They have an osteoconductive effect shortly after implantation. However, dry granules are difficult to handle in the surgical room because of low weight and lack of cohesion. Incorporation of granules in a hydrogel could be a satisfactory solution. We have investigated the use of hyaluronic acid (HyA) as an aqueous binder of the granules. β-TCP granules were prepared by the polyurethane foam technology. Commercially available linear (LHya) and reticulated hyaluronic acid (RHyA) in aqueous solution were used to prepare a pasty mixture that can be handled more easily than granules alone. Thirteen New Zealand White rabbits (3.5–3.75 kg) were used; a 4 mm hole was drilled in each femoral condyle. After flushing, holes were filled with either LHyA, RHyA, dry β-TCP granules alone, β-TCP granules + LHyA and β-TCP granules + RHyA. Rabbits were allowed to heal for one month, sacrificed and femurs were harvested and analysed by microCT and histomorphometry. The net amount of newly formed bone was derived from measurements done after thresholding the microCT images for the material and for the material+bone. LHyA and RHyA did not result in healing of the grafted area. LHyA was rapidly eluted from the grafted zone but allowed deposition of more granules, although the amount of formed bone was not significantly higher than with β-TCP granules alone. RHyA permitted the deposition of more granules which induced significantly more bone trabeculae without inducing an inflammatory reaction. RHyA appears to be a good vehicle to implant granules of β-TCP, since HyA does not interfere with bone remodeling.
A 27 day persistence model of near‐Earth solar wind conditions: A long lead‐time forecast and a benchmark for dynamical models

Geomagnetic activity has long been known to exhibit approximately 27 day periodicity, resulting from solar wind structures repeating each solar rotation. Thus a very simple near‐Earth solar wind forecast is 27 day persistence, wherein the near‐Earth solar wind conditions today are assumed to be identical to those 27 days previously. Effective use of such a persistence model as a forecast tool, however, requires the performance and uncertainty to be fully characterized. The first half of this study determines which solar wind parameters can be reliably forecast by persistence and how the forecast skill varies with the solar cycle. The second half of the study shows how persistence can provide a useful benchmark for more sophisticated forecast schemes, namely physics‐based numerical models. Point‐by‐point assessment methods, such as correlation and mean‐square error, find persistence skill comparable to numerical models during solar minimum, despite the 27 day lead time of persistence forecasts, versus 2–5 days for numerical schemes. At solar maximum, however, the dynamic nature of the corona means 27 day persistence is no longer a good approximation and skill scores suggest persistence is out‐performed by numerical models for almost all solar wind parameters. But point‐by‐point assessment techniques are not always a reliable indicator of usefulness as a forecast tool. An event‐based assessment method, which focusses key solar wind structures, finds persistence to be the most valuable forecast throughout the solar cycle. This reiterates the fact that the means of assessing the “best” forecast model must be specifically tailored to its intended use.
Cellular and animal models for high-throughput screening of therapeutic agents for the treatment of the diseases of the elderly in general and Alzheimer’s disease in particular†

It is currently thought that the dementia of Alzheimer’s disease is due to the neurotoxicity of the deposits or aggregates of amyloid-β (Aβ) in the extracellular space of the cerebral cortex. This model has been widely criticized because there is a poor correlation between deposits and dementia. Others have questioned whether Aβ is truly neurotoxic. Yet, in spite of these concerns, the search for therapeutic agents has been based on the development of mouse models transfected with mutant genes associated in humans with early onset Alzheimer’s disease. A major limitation of these models is that although they exhibit many of the pathological and clinical manifestation of the human disease, the bulk of individuals who develop the dementia of Alzheimer’s disease have none of these mutant genes. Furthermore, nine clinical trials of drugs that were effective in transgenic mice failed to show any benefit in patients. Finally, a major unresolved issue with the Aβ model is that since Aβ is produced in everyone, why are deposits only seen in the elderly? This issue must be resolved if we are to understand the etiology of the disease and develop test systems for both diagnosis and drug discovery. Published studies from my laboratory demonstrate that in human cerebrospinal fluid immunoreactive Aβ is only present as a complex with two chaperones, ERp57 and calreticulin and is N-glycosylated. This complex formation is catalyzed by the posttranslational protein processing system of the endoplasmic reticulum (ER). Others have reported that in plaque Aβ is present only as the naked peptide. Together these results suggest that both plaque and dementia are secondary to an age related decline in the capacity of the ER to catalyze protein, posttranslational processing. Since the synaptic membrane proteins necessary for a functioning memory are also processed in the ER, these findings would suggest that the loss of cognition is due to a decline in the capacity of the neuron to produce and maintain functioning synapses. Work from my laboratory and from others further indicate that the components of the ER, posttranslational, protein processing pathway do dramatically decline with age. These data suggest that this decline may be found in all cells and could account not only for the dementia of Alzheimer’s disease, but also for many of the other manifestations of the aging process. These observations also suggest that declining ER function has a role in two well-recognized phenomena associated with aging: a loss of mitochondrial function and a decrease in myelin. Finally, based on this paradigm I propose new cellular and animals models for high-throughput screening for drug discovery.
Prevention of Migraine During Prodrome With Naratriptan

Objective To determine the role of naratriptan in preventing migraine headache when administered during prodrome. Procedures Baseline phase: patients recorded prodrome symptoms and time of onset, time when patient knew that headache was inevitable, time of onset and severity of headache. Treatment phase: patients given naratriptan 2.5 mg to take at the time they knew headache was inevitable. Patients recorded prodrome symptoms and time of onset, time they knew headache was inevitable, time naratriptan administered, time of onset and severity of any headache. Patients treated three prodromes separated by at least 48 h. Findings Twenty patients completed both phases. During baseline phase, 59 prodromes were reported and all were followed by headache. Severity of headache: 5% mild, 51% moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of these, 38/63 (60%) were not followed by headache. Among headaches that occurred, the majority occurred within 2 h of naratriptan administration, suggesting that naratriptan is more effective in preventing headache if taken early in prodrome. Severity of 25 headaches: 44% mild, 24% moderate, 32% severe. Conclusions Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced. □Prodrome, premonitory, aura, naratriptan, migraine
PROVING SEX DISCRIMINATION IN THE WORKPLACE

Aims to illustrate the difficulties faced by applicants in proving claims of sex discrimination in industrial tribunals. Argues that whilst the more blatant instances of discrimination and prejudice may now be less likely to occur, more subtle and often subconscious forms of sex stereotyping still operate to the disadvantage of working women. Uses recent tribunal decisions to demonstrate an increasing awareness of the problems of proof of discrimination, and an acceptance that inferences of discrimination may be drawn where direct evidence is lacking. Discusses in some detail the case involving the Merseyside Assistant Chief Constable, highlighting the novel use of expert testimony on sex stereotyping and pointing out the significance of such cases for employers. Concludes by suggesting that, despite legal developments, women are unlikely to make significant progress to equality through the use of the law.
Model Predictive Control With a Reduced Number of Considered States in a Modular Multilevel Converter for HVDC System

This paper proposes a model predictive control (MPC) method for modular-multilevel-converter (MMC) high-voltage direct current (HVDC). To control the MMC-HVDC system properly, the ac current, circulating current, and submodule (SM) capacitor voltage are taken into consideration. The existing MPC methods for the MMC-HVDC system utilize weighting factors to configure the cost function in combinations of the SM capacitor voltage balancing algorithm, ac current control, and circulating current control. Because all combinations of the switch states are considered in order to minimize the cost function, their possible combinations increase geometrically according to the increase of the level of the MMC, which is a significant disadvantage. This paper proposes a new MPC method with a reduced number of states for ac current control, circulating current control, and the SM capacitor voltage-balancing algorithm. The proposed cost functions are divided into three types according to their control purposes. Each cost function determines the minimum number of states for controlling the ac current, circulating current, and SM capacitor voltage. The efficacy of the proposed controlling method is verified through simulation results using PSCAD/EMTDC.
Measurement Invariance of the WHODAS 2.0 in a Population-Based Sample of Youth

The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a brief measure of global disability originally developed for adults, which has since been implemented among samples of children and youth. However, evidence of its validity for use among youth, particularly measurement invariance, is lacking. Investigations of measurement invariance assess the extent to which the psychometric properties of observed items in a measure are generalizable across samples. Satisfying the assumption of measurement invariance is critical for any inferences about between-group differences. The objective of this paper was to empirically assess the measurement invariance of the 12-item interview version of the WHODAS 2.0 measure in an epidemiological sample of youth (15 to 17 years) and adults (≥ 18 years) in Canada. Multiple-group confirmatory factor analysis using a categorical variable framework allowed for the sequential testing of increasingly restrictive models to evaluate measurement invariance of the WHODAS 2.0 between adults and youth. Findings provided evidence for full measurement invariance of the WHODAS 2.0 in youth aged 15 to 17 years. The final model fit the data well: χ2(159) = 769.04, p < . 001; CFI = 0.950, TLI = 0.958, RMSEA (90% CI) = 0.055 [0.051, 0.059]. Results from this study build on previous work supporting the validity of the WHODAS 2.0. Findings indicate that the WHODAS 2.0 is valid for making substantive comparisons of disability among youth as young as 15 years of age.
Systematic Risks , Nonlinear Market Models and International Size and Momentum Strategies December 2004

The pricing of systematic risks up to the fourth co-moment of the returns of size and momentum portfolios is investigated. Coskewness and cokurtosis are found to have incremental power in explaining the cross-section of portfolio returns of size and momentum sorts. In particular, model intercepts of the extended higher co-moment CAPM are insignificant in all cases for examining the two-way sorted, momentum-size portfolios. A cubic market model is proposed and tested in time-series which shows better performance than the linear CAPM in explaining the returns of equally weighted portfolios of size and momentum sorts and eight value-weighted country portfolios. In addition, market models are found to predict higher returns for the winner and lower returns for the loser deciles. However, nonlinear market terms do not provide incremental predictability to the linear market model for the next-period realised portfolio returns. A further interesting finding is that the smallest size decile of international stock markets has a positive average return of 1.78% per month in down market periods.