Miracle-dz/UniFAR-FTUs huggingface dataset:
Top-Down Structure Influences Learning of Nonadjacent Dependencies in an Artificial Language

Because of the hierarchical organization of natural languages, words that are syntactically related are not always linearly adjacent. For example, the subject and verb in the child always runs agree in person and number, although they are not adjacent in the sequences of words. Since such dependencies are indicative of abstract linguist structure, it is of significant theoretical interest how these relationships are acquired by language learners. Most experiments that investigate nonadjacent dependency (NAD) learning have used artificial languages in which the to-be-learned dependencies are isolated, by presenting the minimal sequences that contain the dependent elements. However, dependencies in natural language are not typically isolated in this way. We report the first demonstration to our knowledge of successful learning of embedded NADs, in which silences do not mark dependency boundaries. Subjects heard passages of English with a predictable structure, interspersed with passages of the artificial language. The English sentences were designed to induce boundaries in the artificial languages. In Experiment 1 & 3 the artificial NADs were contained within the induced boundaries and subjects learned them, whereas in Experiment 2 & 4, the NADs crossed the induced boundaries and subjects did not learn them. We take this as evidence that sentential structure was “carried over” from the English sentences and used to organize the artificial language. This approach provides several new insights into the basic mechanisms of NAD learning in particular and statistical learning in general.
Haplotype Misclassification Resulting from Statistical Reconstruction and Genotype Error, and Its Impact on Association Estimates

Haplotypes are an important concept for genetic association studies, but involve uncertainty due to statistical reconstruction from single nucleotide polymorphism (SNP) genotypes and genotype error. We developed a re‐sampling approach to quantify haplotype misclassification probabilities and implemented the MC‐SIMEX approach to tackle this as a 3 × 3 misclassification problem. Using a previously published approach as a benchmark for comparison, we evaluated the performance of our approach by simulations and exemplified it on real data from 15 SNPs of the APM1 gene. Misclassification due to reconstruction error was small for most, but notable for some, especially rarer haplotypes. Genotype error added misclassification to all haplotypes resulting in a non‐negligible drop in sensitivity. In our real data example, the bias of association estimates due to reconstruction error alone reached −48.2% for a 1% genotype error, indicating that haplotype misclassification should not be ignored if high genotype error can be expected. Our 3 × 3 misclassification view of haplotype error adds a novel perspective to currently used methods based on genotype intensities and expected number of haplotype copies. Our findings give a sense of the impact of haplotype error under realistic scenarios and underscore the importance of high‐quality genotyping, in which case the bias in haplotype association estimates is negligible.
Troubles psychiatriques, recours au soin et usage de substances psychoactives

Nous avons effectue trois etudes afin (a) d'examiner si le recours au soin modifiait l'intensite du lien entre troubles psychiatriques non lies a une substance et l'usage de substances, et (b) etudier la prevalence et les facteurs associes a l'usage de substance en reponse a un trouble psychiatrique. Nos deux premieres etudes ont montre que le recours au soin etait associe a une diminution du risque de problemes de substances chez les sujets ayant plusieurs troubles non lies a une substance. La troisieme etude a montre que l'usage de substances suite a un trouble psychiatrique etait frequent, en particulier chez les hommes, les sujets avec un bas niveau d'etude, ceux vivant seuls et les plus jeunes. Plus l'etat des sujets etait severe, plus l'usage de substances etait combine a un recours au soin. L'usage de substances sans recours au soin etait plus frequent chez les sujets de moins de 30 ans. Ces etudes pourraient permettre de definir la nature et la cible des campagnes de prevention des troubles lies a une substance.
Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets

ABSTRACT Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses. Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) virus with no history of human infection could become capable of airborne transmission among ferrets. We show that after 10 serial passages, A/H7N1 developed the ability to be transmitted to cohoused and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, and M1 R95K and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the hemagglutinin protein were associated with airborne transmission. Furthermore, transmission was not associated with loss of virulence. These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become capable of airborne transmission in a mammalian host, and they support ongoing surveillance and pandemic H7 vaccine development. IMPORTANCE The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza virus can be adapted to become capable of airborne transmission in mammals without mutations altering receptor specificity. Changes in receptor specificity have been shown to play a role in the ability of avian influenza viruses to cross the species barrier, and these changes are assumed to be essential. The work reported here challenges this paradigm, at least for the influenza viruses of the H7 subtype, which have recently become the focus of major attention, as they have crossed to humans.
Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function

Memory loss resulting from damage to the medial temporal lobes (MTL) is traditionally considered to reflect damage to a dedicated, exclusive memory system. Recent work, however, has suggested that damage to one MTL structure, the perirhinal cortex (PRC), compromises complex object representations that are necessary for both memory and perception. These representations are thought to be critical in shielding against the interference caused by a stream of visually similar input. In this study, we administered a complex object discrimination task to two memory‐impaired populations thought to have brain damage that includes the PRC [patients diagnosed with amnestic mild cognitive impairment (MCI), and older adults at risk for MCI], as well as age‐matched controls. Importantly, we carefully manipulated the level of interference: in the High Interference condition, participants completed a block of consecutive perceptually similar complex object discriminations, whereas in the Low Interference condition, we interspersed perceptually dissimilar objects such that there was less buildup of visual interference. We found that both memory‐impaired populations were impaired on the High Interference condition compared with controls, but critically, by reducing the degree of perceptual interference, we were largely able to improve their performance. These findings, when taken together with convergent evidence from animals with selective PRC lesions and amnesic patients with focal damage to the PRC, provide support for a representational‐hierarchical model of PRC function and suggest that memory loss following PRC damage may reflect a heightened vulnerability to perceptual interference. © 2012 Wiley Periodicals, Inc.
Heart rate variability in childhood obstructive sleep apnea

The identification of patients with obstructive sleep apnea (OSA) is important because of morbidities associated with OSA. A previous adult study demonstrated the use of heart rate variability (HRV) as a tool to identify patients with moderate to severe OSA. Either a reduction in time parameters or an increase in LF/HF ratio was seen at overnight or 24‐hr studies suggestive of increased sympathetic modulation. To study the feasibility of daytime HRV as a screening tool, a short‐term recording of HRV is studied. Since it was shown in adult study that increased normalized LF, decreased normalized HF and increased LF/HF ratio could be detectable during supine rest at daytime awake period, the authors hypothesize that the differences are also detectable in children. Children who underwent sleep polysomnography for suspected OSA were recruited. Subjects were classified OSA if apnea‐hypopnea index (AHI) > 1.5/hr and non‐OSA if AHI ≤ 1.5/hr. Continuous 1‐hr electrocardiographic monitoring was recorded in awake children during the day. Parameters from time domain and frequency domain were analyzed. Seventy‐four male and 17 female snoring subjects were included in this study. Fifty‐one (56%) and 40 (44%) of them were classified as “non‐OSA” and “OSA,” respectively. pNN50, a parameter for parasympathetic modulation, was significantly reduced in the OSA group when compared with the non‐OSA group. Using multiple regression, all time domain variables were shown to be decreased in OSA group. Our results suggest that 1‐hr study of HRV may be a feasible tool in identifying children with OSA. Pediatr Pulmonol. 2011; 46:205–210. © 2011 Wiley‐Liss, Inc.
Convertase activity in alveolar surfactant and lamellar bodies in fetal, newborn, and adult rabbits.

Conversion of heavy-aggregate alveolar surfactant (H) to a light-aggregate, nonsurface active form (L) is believed to involve the activity of an enzyme, namely, convertase. This conversion can be reproduced in vitro by the surface-area cycling technique. The purpose of the present study was to use this technique to investigate the developmental aspects of convertase activity in fetal, newborn, and adult rabbits. H was isolated from alveolar lavage from term [31-day gestation (31d)] fetal rabbit pups, 1-, 4-, and 7-day-old newborns, and adults, and the percent conversion to L was determined. To assess lamellar bodies (LB) as a potential source of activity in this species, these structures were isolated from lung tissue of 27-day-gestation (27d) and 31d fetuses, 1-, 4-, and 7-day-old newborns, and adults and were cycled the same as for H. LB contained considerable activity at each developmental stage i.e., approximately 82% of a 27d LB preparation converted to L after 3 h of cycling. In the adult, this value was 78%. Very little conversion of H was obtained from fetal lung (i.e., <20% of the 31d fetal preparation converted to L), but, by postnatal day 4, this value was greatly increased (i.e., >80% conversion) and stayed elevated to adulthood. The activity for each H and LB fraction was temperature and concentration dependent and diminished with storage at 4 degreesC. These data suggest the LB as the source of convertase activity in the rabbit and demonstrate dramatic developmental changes in this activity after release of the LB contents to the alveoli.
Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children.

AIM To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P = 0.13). CONCLUSIONS HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.
Fetal growth restriction: a modern approach

Purpose of review Fetal growth restriction is a complicated perinatal condition, with multiple causes. It shares common pathophysiologies with other important disorders, such as preeclampsia and abruption. As a group, these conditions associated with ischemic placental disease are responsible for a large percentage of indicated preterm births. The ability to accurately predict, diagnose and manage these pregnancies has significant and far-reaching implications, including potential effects on long-term adult health. Recent findings Placental ischemia is the most common cause of fetal growth restriction. Alterations in placental development are being linked to various angiogenic mediators, which may be of future use in early risk-determination. Until then, the use of ultrasound to accurately diagnose fetal growth restriction and time delivery is the mainstay of management. Research in this area has revealed some commonalities in the deterioration of the growth restricted fetus, but has also indicated that not every affected fetus will follow the same progression in Doppler and other wellbeing parameters. Most importantly, gestational age at delivery is consistently being documented as a critical factor in perinatal morbidity and mortality. Summary Fetal growth restriction is a late manifestation of early abnormal placental development. Once abnormal Doppler velocimetry is present, surveillance and timing of delivery should be based on the antepartum test results and on the gestational age.
Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini.

BACKGROUND & AIMS The present study was undertaken to evaluate the role of serine proteases in regulating digestive enzyme secretion in pancreatic acinar cells. METHODS Isolated acini were stimulated by various secretagogues in the presence or absence of cell-permeant serine protease inhibitors 4-(2-aminoethyl)-benzenesulfonyl fluoride and N(alpha)-p-tosyl-L-phenylalanine chloromethyl ketone. F-actin distribution was studied after staining with rhodamine phalloidin. RESULTS Both cell-permeant serine protease inhibitors blocked amylase secretion in response to secretagogues that use calcium as a second messenger (e.g., cerulein, carbamylcholine, and bombesin) but not to those that use adenosine 3',5'-cyclic monophosphate (cAMP) as a second messenger (e.g., secretin and vasoactive intestinal polypeptide). Incubation of the acini with these inhibitors also resulted in a dramatic redistribution of the F-actin cytoskeleton. This redistribution was energy dependent. Similar redistribution of F-actin from the apical to the basolateral region was also observed when acini were incubated with a supramaximally stimulating concentration of cerulein, which is known to inhibit secretion. CONCLUSIONS These results suggest that a serine protease activity is essential for maintaining the normal apical F-actin distribution; its inhibition redistributes F-actin from the apical to the basolateral region and blocks secretion induced by secretagogues that act via calcium. cAMP reverses the F-actin redistribution and hence cAMP-mediated secretion is not affected.
Schistosoma mansoni and α-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves’ Hyperthyroidism

Graves’ hyperthyroidism, an organ-specific autoimmune disease mediated by stimulatory thyrotropin receptor (TSHR) autoantibodies, has been considered a Th2-dominant disease. However, recent data with mouse Graves’ models are conflicting. For example, we recently demonstrated that injection of BALB/c mice with adenovirus coding the TSHR induced Graves’ hyperthyroidism characterized by mixed Th1 and Th2 immune responses against the TSHR, and that transient coexpression of the Th2 cytokine IL-4 by adenovirus skewed Ag-specific immune response toward Th2 and suppressed disease induction. To gain further insight into the relationship between immune polarization and Graves’ disease, we evaluated the effect of Th2 immune polarization by helminth Schistosoma mansoni infection and α-galactosylceramide (α-GalCer), both known to bias the systemic immune response to Th2, on Graves’ disease. S. mansoni infection first induced mixed Th1 and Th2 immune responses to soluble worm Ags, followed by a Th2 response to soluble egg Ags. Prior infection with S. mansoni suppressed the Th1-type anti-TSHR immune response, as demonstrated by impaired Ag-specific IFN-γ secretion of splenocytes and decreased titers of IgG2a subclass anti-TSHR Abs, and also prevented disease development. Similarly, α-GalCer suppressed Ag-specific splenocyte secretion of IFN-γ and prevented disease induction. However, once the anti-TSHR immune response was fully induced, S. mansoni or α-GalCer was ineffective in curing disease. These data support the Th1 theory in Graves’ disease and indicate that suppression of the Th1-type immune response at the time of Ag priming may be crucial for inhibiting the pathogenic anti-TSHR immune response.
Why Can't A Computer Be More Like A Brain? Or What To Do With All Those Transistors?

By using neuroanatomy and neurophysiology as a set of constraints, we believe that we have started to uncover how the brain uses hierarchy and time to create a model of the world, and to recognize novel patterns as part of that model. Hierarchically-organized memory is fundamentally different than the linear memory used in current computers, and therefore offers the potential for new computer architectures. Today, we are exploring and advancing this technology by using traditional computer architectures (benefited by multiple CPU cores) to emulate the hierarchical structure of the neocortex.
Does Immunotherapy Protect Equines from Reinfection by the Oomycete Pythium insidiosum?

ABSTRACT A cutaneous Pythium insidiosum reinfection was diagnosed in an equine in Brazil. Lesions with focal presentation appeared 2 years apart. The first infection and even immunotherapy were not likely to develop enough immune response to prevent reinfection. The use of adjuvants should be considered in the immunotherapy of pythiosis.
The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

Significance Neuroinflammation and activation of innate immunity are pathological hallmarks of Alzheimer’s disease (AD). In contrast, very few studies have examined the impact of the adaptive immune system in AD pathogenesis. Here, we find that genetic ablation of peripheral immune cell populations significantly accelerates amyloid pathogenesis, worsens neuroinflammation, and alters microglial activation state. Critically, it appears that loss of IgG-producing B cells impairs microglial phagocytosis, thereby exacerbating amyloid deposition. Conversely, replacement of IgGs via direct injection or bone marrow transplantation reverses these effects and reduces Aβ pathology. Together, these results highlight the importance of the adaptive immune system and its interactions with microglia in the pathogenesis of AD. The innate immune system is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting “Rag-5xfAD” mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive–innate immunity cross talk and accelerated disease progression.
Kinase Pathways in Chemoattractant-Induced Degranulation of Neutrophils: The Role of p38 Mitogen-Activated Protein Kinase Activated by Src Family Kinases1

The aim of the present study was to investigate the role of tyrosine phosphorylation pathways in fMLP-induced exocytosis of the different secretory compartments (primary and secondary granules, as well as secretory vesicles) of neutrophils. Genistein, a broad specificity tyrosine kinase inhibitor, blocked the exocytosis of primary and secondary granules, but had only a marginal effect on the release of secretory vesicles. Genistein also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPK), raising the possibility that inhibition of ERK and/or p38 MAPK might be responsible for the effect of the drug on the degranulation response. Indeed, SB203580, an inhibitor of p38 MAPK, decreased the release of primary and secondary granules, but not that of secretory vesicles. However, blocking the ERK pathway with PD98059 had no effect on any of the exocytic responses tested. PP1, an inhibitor of Src family kinases, also attenuated the release of primary and secondary granules, and neutrophils from mice deficient in the Src family kinases Hck, Fgr, and Lyn were also defective in secondary granule release. Furthermore, activation of p38 MAPK was blocked by both PP1 and the hck−/−fgr−/−lyn−/− mutation. Taken together, our data indicate that fMLP-induced degranulation of primary and secondary granules of neutrophils is mediated by p38 MAPK activated via Src family tyrosine kinases. Although piceatannol, a reportedly selective inhibitor of Syk, also prevented degranulation and activation of p38 MAPK, no fMLP-induced phosphorylation of Syk could be observed, raising doubts about the specificity of the inhibitor.