Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroanatomical correlates of phonological processing of Chinese characters and alphabetic words: A meta‐analysis

We used the activation likelihood estimation (ALE) method to quantitatively synthesize data from 19 published brain mapping studies of phonological processing in reading, six with Chinese and 13 with alphabetic languages. It demonstrated high concordance of cortical activity across multiple studies in each written language system as well as significant differences of activation likelihood between languages. Four neural systems for the phonological processing of Chinese characters included: (1) a left dorsal lateral frontal system at Brodmann area (BA) 9; (2) the dorsal aspect of left inferior parietal system; (3) a bilateral ventral‐occipitotemporal system including portions of fusiform gyrus and middle occipital gyrus; and (4) a left ventral prefrontal system covering the superior aspect of inferior frontal gyrus. For phonological processing of written alphabetic words, cortical areas identified here are consistent with the three neural systems proposed previously in the literature: (1) a ventral prefrontal system involving superior portions of left inferior frontal gyrus; (2) a left dorsal temporoparietal system including mid‐superior temporal gyri and the ventral aspect of inferior parietal cortex (supramarginal region); and (3) a left ventral occipitotemporal system. Contributions of each of these systems to phonological processing in reading were discussed, and a covariant learning hypothesis is offered to account for the findings that left middle frontal gyrus is responsible for addressed phonology in Chinese whereas left temporoparietal regions mediate assembled phonology in alphabetic languages. Language form, cognitive process, and learning strategy drive the development of functional neuroanatomy. Hum Brain Mapp 25:83–91, 2005. © 2005 Wiley‐Liss, Inc.
Proteomic Analysis of the Action of the Mycobacterium ulcerans Toxin Mycolactone: Targeting Host Cells Cytoskeleton and Collagen

Buruli ulcer (BU) is a neglected tropical disease caused by Mycobacterium ulcerans. The tissue damage characteristic of BU lesions is known to be driven by the secretion of the potent lipidic exotoxin mycolactone. However, the molecular action of mycolactone on host cell biology mediating cytopathogenesis is not fully understood. Here we applied two-dimensional electrophoresis (2-DE) to identify the mechanisms of mycolactone's cellular action in the L929 mouse fibroblast proteome. This revealed 20 changed spots corresponding to 18 proteins which were clustered mainly into cytoskeleton-related proteins (Dync1i2, Cfl1, Crmp2, Actg1, Stmn1) and collagen biosynthesis enzymes (Plod1, Plod3, P4ha1). In line with cytoskeleton conformational disarrangements that are observed by immunofluorescence, we found several regulators and constituents of both actin- and tubulin-cytoskeleton affected upon exposure to the toxin, providing a novel molecular basis for the effect of mycolactone. Consistent with these cytoskeleton-related alterations, accumulation of autophagosomes as well as an increased protein ubiquitination were observed in mycolactone-treated cells. In vivo analyses in a BU mouse model revealed mycolactone-dependent structural changes in collagen upon infection with M. ulcerans, associated with the reduction of dermal collagen content, which is in line with our proteomic finding of mycolactone-induced down-regulation of several collagen biosynthesis enzymes. Our results unveil the mechanisms of mycolactone-induced molecular cytopathogenesis on exposed host cells, with the toxin compromising cell structure and homeostasis by inducing cytoskeleton alterations, as well as disrupting tissue structure, by impairing the extracellular matrix biosynthesis.
Discovering emerging entities with ambiguous names

Knowledge bases (KB's) contain data about a large number of people, organizations, and other entities. However, this knowledge can never be complete due to the dynamics of the ever-changing world: new companies are formed every day, new songs are composed every minute and become of interest for addition to a KB. To keep up with the real world's entities, the KB maintenance process needs to continuously discover newly emerging entities in news and other Web streams. In this paper we focus on the most difficult case where the names of new entities are ambiguous. This raises the technical problem to decide whether an observed name refers to a known entity or represents a new entity. This paper presents a method to solve this problem with high accuracy. It is based on a new model of measuring the confidence of mapping an ambiguous mention to an existing entity, and a new model of representing a new entity with the same ambiguous name as a set of weighted keyphrases. The method can handle both Wikipedia-derived entities that typically constitute the bulk of large KB's as well as entities that exist only in other Web sources such as online communities about music or movies. Experiments show that our entity discovery method outperforms previous methods for coping with out-of-KB entities (called unlinkable in entity linking).
Anandamide suppresses nitric oxide and TNF‐α responses to Theiler's virus or endotoxin in astrocytes

ASTROCYTES are an important cell population in the CNS, involved in cytokine homeostasis and participating in a variety of important physiological and pathological processes. In the present study we showed that primary cultures of neonatal mouse cortical astrocytes stimulated with lipopolysaccharide (Balb/c mice strain, LPS: 1 μg/ml, 18 h) or Theiler's virus, TMEV (SJL/J mice strain, TMEV: 105 PFU/well, 24 h) released an increased amount of nitrites (NO2−) and tumour necrosis factor-α (TNF-α) into the culture medium. Exogenous cannabinoids are known to modulate the function of immune cells. Anandamide, an endogenous ligand for the cannabinoid receptor, blocked the release of NO2− and TNF-α induced by LPS in a dose-dependent manner. In TMEV-stimulated astrocytes anandamide also suppressed, in a dose-related manner, the stimulatory effects of TMEV on both NO2− and TNF-α. It is suggested that anandamide exerts an immunoregulatory role in the CNS. These results could have important implications in the modulation of immunological and inflammatory processes by cannabinoid agents.
The optimal therapy of calcineurin inhibitors for pregnancy in kidney transplantation

We investigated the effects of pregnancy and delivery on renal function in transplant recipients and the relationship between doses of immunosuppressants and blood drug levels during pregnancy in 75 women with 88 deliveries. Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight deliveries. In the remaining 80 cases, serum creatinine was reduced by an average of 0.14 mg/dL and returned to pre‐pregnant levels after delivery. Tacrolimus was used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level declined from 5.8 ± 2.8 ng/mL 12 months before delivery to 4.2 ± 1.8 ng/mL at second trimester; therefore, drug dose was increased from 4.1 ± 1.9 mg/d at first trimester to 5.5 ± 2.5 mg/d at delivery. Similarly, cyclosporine levels were 125.1 ± 65.1 ng/mL 12 months before delivery and 75.4 ± 35.0 ng/mL at second trimester resulting in dose elevation from 183.0 ± 71.8 mg/d at first trimester to 225.4 ± 85.1 mg/d at delivery. Renal function in female kidney transplant recipients improved slightly during pregnancy and returned to pre‐pregnant level after delivery. The dose elevation of calcineurin inhibitor by approximately 20–25% should be considered during gestational period to maintain optimal blood drug level.
Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models

Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials. This article is part of the themed issue ‘Evolutionary ecology of arthropod antimicrobial peptides’.
Regulation of Early Events in Integrin Signaling by Protein Tyrosine Phosphatase SHP-2

ABSTRACT The nontransmembrane protein tyrosine phosphatase SHP-2 plays a critical role in growth factor and cytokine signaling pathways. Previous studies revealed that a fraction of SHP-2 moves to focal contacts upon integrin engagement and that SHP-2 binds to SHP substrate 1 (SHPS-1)/SIRP-1α, a transmembrane glycoprotein with adhesion molecule characteristics (Y. Fujioka et al., Mol. Cell. Biol. 16:6887–6899, 1996; M. Tsuda et al., J. Biol. Chem. 273:13223–13229). Therefore, we asked whether SHP2–SHPS-1 complexes participate in integrin signaling. SHPS-1 tyrosyl phosphorylation increased upon plating of murine fibroblasts onto specific extracellular matrices. Both in vitro and in vivo studies indicate that SHPS-1 tyrosyl phosphorylation is catalyzed by Src family protein tyrosine kinases (PTKs). Overexpression of SHPS-1 in 293 cells potentiated integrin-induced mitogen-activated protein kinase (MAPK) activation, and potentiation required functional SHP-2. To further explore the role of SHP-2 in integrin signaling, we analyzed the responses of SHP-2 exon 3−/− and wild-type cell lines to being plated on fibronectin. Integrin-induced activation of Src family PTKs, tyrosyl phosphorylation of several focal adhesion proteins, MAPK activation, and the ability to spread on fibronectin were defective in SHP-2 mutant fibroblasts but were restored upon SHP-2 expression. Our data suggest a positive-feedback model in which, upon integrin engagement, basal levels of c-Src activity catalyze the tyrosyl phosphorylation of SHPS-1, thereby recruiting SHP-2 to the plasma membrane, where, perhaps by further activating Src PTKs, SHP-2 transduces positive signals for downstream events such as MAPK activation and cell shape changes.
Improving the performance of overlay multicast with dynamic adaptation

Overlay multicast protocols should adapt to the dynamic network environment to maintain application performance. We show how end-to-end network metrics can be used in the dynamic adaptation and thus improve the performance of the direct-tree overlay multicast protocols while providing good tree quality. We propose the adaptive overlay multicast (AOM) approach that provides good tree quality and efficient adaptation. We compare AOM with a typical direct-tree protocol like HMTP (host multicast tree protocol). The simulation results show that AOM builds high-quality trees, adapts better to network conditions and is efficient.
A Thorough QTc Study of 3 Doses of Iloperidone Including Metabolic Inhibition Via CYP2D6 and/or CYP3A4 and a Comparison to Quetiapine and Ziprasidone

Abstract The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate–corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1:1:1:1:1 to iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5–9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc ≥500 ms). The most common adverse events with iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with iloperidone were non–concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.
Oral zinc therapy for zinc deficiency‐related telogen effluvium

Zinc is crucial for maintaining human body homeostasis and is one of the major components of hormones, signal molecules, and enzymes. Zinc deficiency is caused by insufficient uptake of zinc from food, or caused by malabsorption syndromes, increased gastrointestinal and urinary losses, and administration of various medications. In order to test whether oral zinc administration can successfully improve zinc deficiency‐related alopecia, we treated five patients with zinc deficiency‐related telogen effluvium with oral zinc administration in the form of polaprezinc (Promac®). In all patients, hair loss was cured or improved. The administration of zinc for zinc deficiency‐related alopecia may recover appropriate activities of metalloenzymes, hedgehog signaling, and immunomodulation, all of which are required for normal control of hair growth cycle.
Catastrophic Catecholamine-Induced Cardiomyopathy Mimicking Acute Myocardial Infarction, Rescued by Extracorporeal Membrane Oxygenation (ECMO) in Pheochromocytoma

Pheochromocytoma is a rare disorder and functioning tumor composed of chromaffin cells that secrete catecholamines. Patients with a pheochromocytoma 'crisis' have a high mortality in spite of aggressive therapy. We present a case with a severe acute catecholamine cardiomyopathy presenting ST segment elevation with cardiogenic shock after hemorrhage into a left suprarenal tumor. Intra-aortic balloon pump (IABP) support, combined with inotropic therapy, was performed. However, the patient deteriorated rapidly and was unresponsive to a full dose of inotropics and IABP. We decided to apply extracorporeal membrane oxygenation (ECMO) device for the patient. His clinical state began to improve 3 days after ECMO. After achieving hemodynamic stabilization, he underwent successful laparoscopic left adrenalectomy. He needed no further cardiac medication after discharge.
Continuous versus discrete information processing modeling accumulation of partial information.

David Meyer and colleagues have recently developed a new technique for examining the time course of information processing. The technique is a variant of the response signal procedure: On some trials subjects are presented with a signal that requires them to respond, whereas on other trials they respond normally. These two types of trials are randomly intermixed so subjects are unable to anticipate which kind of trial is to be presented next. For data analysis, it is assumed that on the signal trials observed reaction times are a probability mixture of regular responses and guesses based on partial information. The accuracy of guesses based on partial information can be determined by using the data from the regular trials and a simple race model to remove the contribution of fastfinishing regular trials from signal trial data. This analysis shows that the accuracy of guesses is relatively low and is either approximately constant or grows slowly over the time course of retrieval. Meyer and colleagues have argued that this pattern of results rules out most continuous models of information processing. But the analyses presented in this article show that this pattern is consistent with several stochastic reaction time models': the simple random walk, the runs, and the continuous diffusion models. The diffusion model is assessed with data from a new experiment using the studytest recognition memory procedure. Fitting the diffusion model to the data from regular trials fixes all parameters of the model except one (the signal encoding and decision parameter). With this one free parameter, the model predicts the observed guessing accuracy. In summary, results obtained from Meyer et al? s (1988) new technique give important qualitative support to some stochastic models and impressive quantitative support to the continuous diffusion model.
Fiber Bragg Gratings for Sensing Temperature and Stress in Superconducting Coils

We study the feasibility of employing fiber Bragg gratings (FBG) for measuring thermodynamics parameters of superconducting coils. The distributions of mechanical stress and temperature inside the coil are important for an optimized design. Standard sensors with electrical connections like resistance thermometer and strain gauges cannot be placed inside the coil. So it is impossible to access local stress and temperature data. Bragg gratings fabricated at different location in one fiber is better suited for this purpose. Five-mm long gratings with different spatial period are arranged at various positions along a single mode fiber inside the coil. Coil temperature and stress will vary the gratings periods, which can be read out with a tunable laser in a wavelength division-multiplexing (WDM) scheme. The spectral position of the reflections may be correlated with the spatial position of the gratings, and the shift of the gratings' maximum reflection indicates the change of the gratings' period, which in turn measures temperature or stress. We specify the design and technology requirements to adapt the FBG sensor concept for low temperature near 4 K. Initial experiments, which demonstrate the properties of glass FBG at low temperatures, are reported
Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up‐regulated in myeloid cells by 1,25‐dihydroxyvitamin D3

The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the α‐ and β‐defensins and cathelicidins. In this study, we show that 1,25‐dihydroxyvitamin D3 and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM) ‐derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR‐deficient bone marrow was similar to wild‐type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25‐dihydroxyvitamin D3 and the VDR in regulation of primate innate immunity. Gombart, A. F. , Borregaard, N. , Koeffler, H. P. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up‐regulated in myeloid cells by 1,25‐dihydroxyvitamin D3. FASEB J. 19, 1067–1077 (2005)
Old men running: mechanical work and elastic bounce

It is known that muscular force is reduced in old age. We investigate what are the effects of this phenomenon on the mechanics of running. We hypothesized that the deficit in force would result in a lower push, causing reduced amplitude of the vertical oscillation, with smaller elastic energy storage and increased step frequency. To test this hypothesis, we measured the mechanical energy of the centre of mass of the body during running in old and young subjects. The amplitude of the oscillation is indeed reduced in the old subjects, resulting in an approximately 20% smaller elastic recovery and a greater step frequency (3.7 versus 2.8 Hz, p=1.9×10−5, at 15–17 km h−1). Interestingly, the greater step frequency is due to a lower aerial time, and not to a greater natural frequency of the system, which is similar in old and young subjects (3.6 versus 3.4 Hz, p=0.2). Moreover, we find that in the old subjects, the step frequency is always similar to the natural frequency, even at the highest speeds. This is at variance with young subjects who adopt a step frequency lower than the natural frequency at high speeds, to contain the aerobic energy expenditure. Finally, the external work to maintain the motion of the centre of mass is reduced in the old subjects (0.9 versus 1.2 J kg−1 m−1, p=5.1×10−6) due to the lower work done against gravity, but the higher step frequency involves a greater internal work to reset the limbs at each step. The net result is that the total work increases with speed more steeply in the old subjects than in young subjects.
Recent trends in occupational segregation by Gender: a look across the Atlantic

In this paper, we analyse the recent patterns of occupational segregation by gender in the EU countries vis-a-vis the US. Given the lack of long time-series data on homogeneous LFS data about occupations and educational attainments for male and female workers in EU countries, we use a single cross section corresponding to 1999 as the basis of comparison, hoping to uncover covergence trends by examining whether the EU-Us differentials in gender occupational segregation decline across age cohorts. The main findings of our study are: (i) gender segregation has been declining across age cohorts in the case of female graduates and has remained steady for those with lower educational levels; in particular, the level ot segregation for the former group is higher in the EU than in the US; (ii) gender segregation seems to be positively correlated with the share of part-time jobs; and (iii) there is some evidence, albeit a weak one, that the gender wage gap and occupational segregation are positively correlated, particularly when the Scandinavian countries are excluded from the sample.