Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of a Novel Toxoplasma gondii Conoid-Associated Protein Important for Parasite Resistance to Reactive Nitrogen Intermediates

Toxoplasma gondii modifies its host cell to suppress its ability to become activated in response to IFN-γ and TNF-α and to develop intracellular antimicrobial effectors, including NO. Mechanisms used by T. gondii to modulate activation of its infected host cell likely underlie its ability to hijack monocytes and dendritic cells during infection to disseminate to the brain and CNS where it converts to bradyzoites contained in tissue cysts to establish persistent infection. To identify T. gondii genes important for resistance to the effects of host cell activation, we developed an in vitro murine macrophage infection and activation model to identify parasite insertional mutants that have a fitness defect in infected macrophages following activation but normal invasion and replication in naive macrophages. We identified 14 independent T. gondii insertional mutants out of >8000 screened that share a defect in their ability to survive macrophage activation due to macrophage production of reactive nitrogen intermediates (RNIs). These mutants have been designated counter-immune mutants. We successfully used one of these mutants to identify a T. gondii cytoplasmic and conoid-associated protein important for parasite resistance to macrophage RNIs. Deletion of the entire gene or just the region encoding the protein in wild-type parasites recapitulated the RNI-resistance defect in the counter-immune mutant, confirming the role of the protein in resistance to macrophage RNIs.
Alteration of a model antigen by Au(III) leads to T cell sensitization to cryptic peptides

Certain metal ions are known to be potent sensitizers, but the self proteins modified by metal ions and the self peptides recognized by ‘metal‐specific’ T cells are unknown. In humans and mice treatment with gold anti‐rheumatic drugs, containing Au(I), may lead to allergic and autoimmune side effects. Human and murine T cells do not react to Au(I), however, but to the reactive metabolite Au(III). Here we show that alteration by Au(III) of a model antigen, bovine ribonuclease (RNase) A, results in T cell sensitization to cryptic peptides of this protein. Upon immunization of mice with Au(III)‐pretreated RNase [RNase/Au(III)], CD4+ T cell hybridomas specific for RNase/Au(III) were obtained in addition to those recognizing the immunodominant peptide RNase 74–88; the latter also were obtained after immunization with native RNase. RNase/Au(III)‐specific T cell hybridomas reacted against RNase/Au(III) and RNase denatured by S‐sulfonation of cysteine residues, but not against native RNase, or RNase pretreated with Au(I), Al(III), Cu(II), Fe(II), Fe(III), Ni(II), Mn(II), or Zn(II). Using a panel of overlapping, synthetic RNase peptides which were devoid of gold or gold‐induced modifications, epitope mapping revealed that RNase/Au(III)‐specific T cell hybridomas recognized the cryptic peptides 7–21 and 94–108, respectively. Comparison of the proliferative response of bulk CD4+ T cells, prepared from splenocytes after immunization with either RNase/Au(III) or native RNase, revealed that Au(III) pretreatment of RNase led to a markedly enhanced response to the two cryptic peptides while it did not influence the response to the immunodominant peptide. The cryptic peptides were also presented after preincubation of bone marrow‐derived macrophages with RNase and Au(I), but not with RNase alone, suggesting that oxidation of Au(I) to Au(III) and subsequent protein alteration by Au(III) can happen in mononuclear phagocytes. We conclude that Au(III) alteration of proteins alters antigen processing and, thus, leads to presentation of cryptic peptides. This mechanism may shed light on the development of allergic and autoimmune side effects of Au(I) anti‐rheumatic drugs. In addition, it might provide a general mechanism of how metal ions act as T cell sensitizers.
Analysis of Tuition Growth Rates Based on Clustering and Regression Models

Tuition plays a significant role in determining whether a student could afford higher education, which is one of the major driving forces for country development and social prosperity. So it is necessary to fully understand what factors might affect the tuition and how they affect it. However, many existing studies on the tuition growth rate either lack sufficient real data and proper quantitative models to support their conclusions, or are limited to focus on only a few factors that might affect the tuition growth rate, failing to make a comprehensive analysis. In this paper, we explore a wide variety of factors that might affect the tuition growth rate by use of large amounts of authentic data and different quantitative methods such as clustering and regression models.
Lymphatic vascular morphogenesis in development, physiology, and disease

The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many common pathological conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development and genetically engineered animal models coupled with the discovery of mutations underlying human lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel therapies for human diseases.
Hands, hover, and nibs: understanding stylus accuracy on tablets

Although tablets and styli have become pervasive, styli have not seen widespread adoption for precise input tasks such as annotation, note-taking, algebra, and so on. While many have identified that stylus accuracy is a problem, there is still much unknown about how the user and the stylus itself influences accuracy. The present work identifies a multitude of factors relating to the user, the stylus, and tablet hardware that impact the inaccuracy experienced today. Further, we report on a two-part user study that evaluated the interplay between the motor and visual systems (i.e., hand posture and visual feedback) and an increasingly important feature of the stylus, the nib diameter. The results determined that the presence of visual feedback and the dimensions of the stylus nib are crucial to the accuracy attained and pressure exerted with the stylus. The ability to rest one's hand on the screen, while providing comfort and support, was found to have surprisingly little influence on accuracy.
Frequency domain analysis of lamb wave scattering and application to film bulk acoustic wave resonators

This paper demonstrates a novel frequency domain analysis (FDA) to evaluate the scattering behavior of a waveguide mode at arbitrary scattering geometries by a time harmonic simulation based on the finite element method (FEM). To this end, we add an injection-damping mechanism (IDM) to avoid interference at the acoustic input port. The IDM can be easily constructed by a numerical operation. Our approach offers improved time consumption and calculation power necessary over the established method in the time domain. After checking the validity of the proposed method, we discuss the importance of considering wave scattering phenomena in film bulk acoustic wave resonator (FBAR) devices by applying the proposed method to two simplified models of an FBAR device.
Doppler Ultrasound in Mice

Color, power, spectral, and tissue Doppler have been applied to mice. Due to the noninvasive nature of the technique, serial intraindividual Doppler measurements of cardiovascular function are feasible in wild‐type and genetically altered mice before and after microsurgical procedures or to follow age‐related changes. Fifty‐megahertz ultrasound biomicroscopy allows to record the first beats of the embryonic mouse heart at somite stage 5, and the first Doppler‐flow signals can be recorded after the onset of intrauterine cardiovascular function at somite stage 7. Using 10‐ to 20‐MHz ultrasound transducers in the mouse embryo, cardiac, and circulatory function can be studied as early as 7.5 days after postcoital mucous plug. Postnatal Doppler ultrasound examinations in mice are possible from birth to senescent age. Several strain‐, age‐, and gender‐related differences of Doppler ultrasound findings have been reported in mice. Results of Doppler examinations are influenced by the experimental settings as stress testing or different forms of anesthesia. This review summarizes the present status of Doppler ultrasound examinations in mice and animal handling in the framework of a comprehensive phenotype characterization of cardiac contractile and circulatory function.
Genetic susceptibility to leishmanial infections: studies in mice and man

SUMMARY Two important recent advances in Leishmania immunology are: (i) the demonstration of a dramatic dichotomy in T helper 1 versus T helper 2 subset expansion leading to protection versus disease exacerbation; and (ii) analysis of the macrophage activation pathways leading to enhanced intracellular killing of parasites, in particular the tumour necrosis factor α (TNFα)-dependent sustained induction of the inducible nitric oxide synthase gene (Nos2) leading to the generation of large amounts of nitric oxide (NO). Given the broad spectrum of disease phenotypes in human leishmaniasis, one might predict that a genetic defect at any key point in this macrophage activation pathway and/or in pathways leading to activation of different T cell subsets, and the latter may be a pleiotropic effect of the former, will contribute to disease susceptibility. By studying disease in genetically-defined inbred mouse strains, it has been possible to identify 5 regions of the murine genome carrying leishmanial susceptibility genes. The genes include: (i) Scl-2 (mouse chromosme 4/human chromosome 9p; candidate Janus tyrosine kinase 1) controlling a unique no lesion growth resistance phenotype to Leishmania mexicana; (ii) Scl-1 (distal mouse chromosome 11/human 17q; candidates Nos2, Sigje, MIP1α, MIP1β) controlling healing versus non-healing responses to L. major; (iii) the ‘T helper 2’ cytokine gene cluster (proximal murine chromosome 11/human 5p; candidates IL4,5,9) controlling later phases of L. major infection; (iv) the major histocompatibility complex (MHC: H-2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNFα/β genes); and (v) Nramp1, the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35). This review examines these 5 regions and the candidate genes within them, reflecting on their current status as candidates for human disease susceptibility genes.
Blood–brain barrier impairment in Alzheimer disease

Objective: To determine the stability and functional significance of blood–brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD). Methods: Thirty-six patients (mean age 71 ± 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 ± 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF–albumin index (CSF-AI). Results: BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r2 = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r2 = 0.29, p = 0.001), and annual ventricular volume change (r2 = 0.17, p = 0.007). Conclusions: Blood–brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF–albumin index and measures of disease progression over 1 year.
E-Inclusion Strategies in Public Administrations: Experiences from Regional Governments in Spain

The implementation of e-Government could reduce administrative costs and the time devoted to repetitive tasks by civil servants, offering greater transparency to public administration, improving the current performance of public sector services, and expanding access to services. However, previous research indicates that there are significant barriers for citizens, assuming major obstacles. In this sense, the EU and, in particular, the Spanish government has formulated policies and legal frameworks to introduce in the field of the provision of public sector services in order to customize and to access these services. Therefore, the purpose of this chapter is to obtain a vision of government strategies adopted by Spanish regional governments to reduce the digital divide.
Treatment of disseminated intravascular coagulation in acute promyelocytic leukemia with low molecular weight heparinoid org 10172

Four patients with acute promyelocytic leukemia (APL) and clinical and laboratory manifestations of disseminated intravascular coagulation (DIC) were treated during induction chemotherapy with Org 10172 (Organon International), a low molecular weight heparinoid preparation. Plasma anti‐Xa levels were maintained between 0.60 and 0.80 U/ml and anticoagulant activities, determined with a diluted activated partial thromboplastin time assay, ranged from 0.00 to 0.20 U/ml. Bleeding symptoms ceased and fibrinogen levels improved in the first week in all patients. In the second week, two patients developed bleeding as a result of primary fibrinolysis. It is concluded that Org 10172 may be useful in the treatment of patients with DIC. In patients with APL, inhibition of DIC will be insufficient to control all bleeding, since primary fibrinolysis may also occur.Cancer 58:761‐764, 1986.
Blocking of Proteolytic Processing and Deletion of Glycosaminoglycan Side Chain of Mouse DMP1 by Substituting Critical Amino Acid Residues

Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH<sub>2</sub>- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH<sub>2</sub> termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp<sup>181</sup> (corresponding to Asp<sup>197</sup> of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH<sub>2</sub> terminus of Asp<sup>197</sup> of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp<sup>197</sup> is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp<sup>197</sup> with Ala<sup>197</sup> by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH<sub>2</sub> terminus of Asp<sup>197</sup> is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH<sub>2</sub>-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser<sup>74</sup> in rat DMP1 (Ser<sup>89</sup> in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser<sup>89</sup>, we substituted Ser<sup>89</sup> by Gly<sup>89</sup>. Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser<sup>89</sup> in mouse DMP1.
Noise Composition Test of Stock Prices with NCT: Evidence from Seven Asian Stock Markets

Based on the variance-ratio test of Lo and Mackinlay(1988,1989),I construct a noise composition test(NCT) index in this paper and give an empirical test to seven Asian stock markets.I find the the markets of mainland of China and Thailand have more noise composition and are more inefficient.Meanwhile,the markets of Hong Kong,Taiwan,and Japan have a smaller noise composition and I cannot reject the zero hypothesis of price which is following a random walk.At last,I use the Bootstrap sample to re-estimate the previous results and find it is robust.
Let It “B”? The Role of Hepatitis B Universal Vaccination among Italian Problematic Drug Users

Hepatitis B virus (HBV) hepatitis is extremely common among problematic drug users (DUs). As of 2012, 47 of the 53 European countries had implemented a universal hepatitis B vaccination programme, a scenario that could radically change its spread. Even so, drug users are still one of the main groups at risk of being infected by HBV, exposing the fact that universal vaccination still has not managed to reach an optimal level of contagion protection. In order to evaluate the role of universal HBV vaccination in protecting against risk behaviour related to the use of illicit drugs, a group of 748 DUs, 511 male and 237 female, was tested for HBV markers, at their first access to public addiction clinics in the metropolitan area of Bologna, Italy. 487 were born after 1981, so they were eligible to have received HBV vaccination in adolescence or at birth; in these subjects antibodies against HBV core antigen had the significant prevalence of 6.2%. Universal HBV vaccination has shown evidence of protecting against infection in the general population. These results, amongst the first to evaluate actual protection in DUs vaccinated at birth or during adolescence, show that compulsory universal vaccination does not solve the problem of HBV transmission in the most at risk groups and that additional strategies must be studied and implemented to address this issue.
Separation of Function between Isotype Switching and Affinity Maturation In Vivo during Acute Immune Responses and Circulating Autoantibodies in UNG-Deficient Mice

Activation-induced deaminase converts deoxycytidine to deoxyuridine at the Ig loci. Complementary pathways, initiated by the uracil-DNA glycosylase (UNG) or the mismatch repair factor MSH2/MSH6, must process the deoxyuridine to initiate class-switch recombination (CSR) and somatic hypermutation. UNG deficiency most severely reduces CSR efficiency and only modestly affects the somatic hypermutation spectrum in vitro. This would predict isotype-switching deficiency but normal affinity maturation in Ung−/− mice in vivo, but this has not been tested. Moreover, puzzling differences in the amount of circulating Ig between UNG-deficient humans and mice make it unclear to what extent MSH2/MSH6 can complement for UNG in vivo. We find that Ab affinity maturation is indeed unaffected in Ung−/− mice, even allowing IgM responses with higher than normal affinity. Ung−/− mice display normal to only moderately reduced basal levels of most circulating Ig subclasses and gut-associated IgA, which are elicited in response to chronically available environmental Ag. In contrast, their ability to produce switched Ig in response to immunization or vesicular stomatitis virus infection is strongly impaired. Our results uncover a specific need for UNG in CSR for timely and efficient acute Ab responses in vivo. Furthermore, Ung−/− mice provide a novel model for separating isotype switching and affinity maturation during acute (but not chronic) Ab responses, which could be useful for dissecting their relative contribution to some infections. Interestingly, Ung−/− mice present with circulating autoantibodies, suggesting that UNG may impinge on tolerance.
An examination of similarity neighbourhoods in young children's receptive vocabularies

ABSTRACT Based on an analysis of similarity neighbourhoods of words in children's lexicons, Dollaghan (1994) argues that because of the degree of phonological overlap among lexical items in memory, children must perform detailed acoustic-phonetic analyses in order to recognize spoken words. This is in contradiction to Charles-Luce & Luce (1990), who reported that the similarity neighbourhoods in younger children's expressive lexicons are sparse relative to older children's and adult lexicons and that young children may be able to use more global word recognition strategies. The current investigation re-examined these issues. Similarity neighbourhoods of young children's RECEPTIVE vocabularies were analysed for three-phoneme, four-phoneme and five-phoneme words. The pattern of the original results from Charles-Luce & Luce (1990) was replicated.
Asymptotic normality of the sample convariances of evanescent fields in noise

We consider the asymptotic properties of the sample covariance sequence of a field composed of the sum of evanescent components and a purely-indeterministic component. In this framework a Bartlett-type formula for the covariance function of the sample covariances of a horizontal evanescent field observed in the presence of a purely-indeterministic field, is derived. The asymptotic normality of the sample covariances is established
Regulation of target genes of PAX3-FOXO1 in alveolar rhabdomyosarcoma.

BACKGROUND The majority of alveolar rhabdomyosarcoma (ARMS) are distinguished through the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncoprotein, being generated by a 2;13 chromosomal translocation. This fusion-positive ARMS is the most clinically difficult type of rhabdomyosarcoma. The present study characterized four genes [gremlin 1 (GREM1), death-associated protein kinase-1 (DAPK1), myogenic differentiation-1 (MYOD1), and hairy/enhancer-of-split related with YRPW motif-1 (HEY1)] as targets of PAX3-FOXO1. MATERIALS AND METHODS The expression of the four genes, PAX3-FOXO1, and v-myc myelocytomatosis viral-related oncogene, neuroblastoma-derived (avian) (MYCN) was determined in various ARMS cell models and primary tumors. The roles of PAX3-FOXO1 and MYCN expression were examined. RESULTS Pulse-chase and cycloheximide experiments suggest that GREM1, DAPK1, and MYOD1 are directly regulated by PAX3-FOXO1. PAX3-FOXO1 appears to indirectly down-regulate HEY1 by up-regulating MYCN. Data reveal that the growth-suppressive activity of high PAX3-FOXO1 expression is closely-associated with up-regulation of the GREM1 and DAPK1 tumor-suppressor genes. CONCLUSION This study characterized four downstream targets of PAX3-FOXO1 that contribute to the biological activities of growth suppression and myogenic differentiation.
Notice of RetractionA Model of Mechanisms of Cellular Defending Genome Stress Based on KTAP Framework

Under acute perturbations from outer environment, a mathematical model of cellular self-defense mechanisms is proposed by using the method of Kinetic Theory of Active Particles (KTAP). In the processes of DNA damage repair, DNA damage and Repair Protein (RP) generating, DSBC synthesizing are implemented by the particle interactions between the pairs of DNA and acute Ion Radiation (IR), DNA damage and RP. Furthermore, cellular self-repair capability, cellular activity and genome stability are analyzed under different IR dose domains.