Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Analysis of Signal Transduction by CD40 and the Epstein-Barr Virus Oncoprotein LMP1 In Vivo

ABSTRACT There is much evidence, based primarily on in vitro studies, indicating that the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1) mimics an activated CD40 receptor. In order to investigate the extent of similarity between LMP1 and CD40 functions in vivo, we analyzed the cytoplasmic signaling properties of LMP1 and CD40 in B cells in a directly comparable manner. For this purpose, we generated transgenic mice expressing either LMP1 or a chimeric LMP1CD40 molecule, which constitutively activates the CD40 pathway, under the control of the CD19 promoter. LMP1 and LMP1CD40 were expressed at similar levels in a B-lymphocyte-specific manner. Similar to LMP1, LMP1CD40 suppressed germinal center (GC) formation and antibody production in response to thymus-dependent antigens, albeit to a greater extent than LMP1. Furthermore, the avidity of the antibodies produced against thymus-dependent antigens was lower for LMP1CD40 transgenic mice than for wild-type and LMP1 transgenic mice. GC suppression was linked to the ability of LMP1CD40 and LMP1 to downregulate mRNA and protein levels of BCL6 and to suppress the activity of the BCL6 promoter. In contrast to LMP1, LMP1CD40 caused an upregulation of CD69, CD80, and CD86 in B cells and a dramatic increase in serum immunoglobulin M. In addition, LMP1CD40 but not LMP1 transgenic mice had elevated numbers of marginal-zone B cells and increased populations of polymorphonuclear cells and/or neutrophils. Consistent with these findings, LMP1CD40 but not LMP1 transgenic mice showed signs of spontaneous inflammatory reactions and the potential for autoimmunity.
Concise review of the glutathione S-transferases and their significance to toxicology.

The glutathione S-transferases (GSTs; E.C. 2.5.1.18) are a multi-gene family of enzymes involved in the detoxification, and, in a few instances, activation of a wide variety of chemicals (Table 1). Since their discovery in the early 1970s, thousands of articles have been written on the structure, function, and toxicologic significance of GSTs, and it is obviously beyond the scope of this article to provide a comprehensive review of the field. This article will highlight the major features of this multi-gene family of enzymes, with a focus on human soluble (cytosolic) GSTs. A relatively comprehensive review of the GSTs was published in 1995, and provides an excellent source for detailed information and references about nearly all aspects of GSTs up to that time (Hayes and Pulford, 1995). (Because of space limitations, the present mini-review is not fully referenced, but it does include some newer references not covered in previous reviews.) GSTs catalyze the nucleophilic attack of glutathione (GSH) on electrophilic substrates, thereby decreasing their reactivity with cellular macromolecules (Armstrong, 1997). These proteins have been found in virtually every living species examined, including plants, animals, and bacteria (Hayes and Pulford, 1995). Most GSTs exist as soluble enzymes, although a small family of microsomal GSTs has been characterized (Andersson et al., 1994; Jakobsson et al., 1996), and a mitochondrial GST, referred to as GST Kappa, has also been identified (Pemble et al., 1996). In humans and in rodents, the soluble GSTs are collectively expressed in rather large amounts, constituting as much as 4% of total soluble protein in the liver. Although no definitive physiological role for GSTs has yet been identified, several reactive endogenous molecules, including ab-unsaturated keto prostaglandins (e.g., PGA2, PGJ2), and endogenous fatty acid oxidation products, such as 4-hydroxy-2-nonenal, serve as substrates for certain GSTs (Hayes and Pulford, 1995) (Table 2). One human GST (hGSTM2-2) has recently been found to exhibit unique and high catalytic activity toward reactive quinones of endogenous catecholamines (e.g., dopaminochrome, formed by oxidation of dopamine), and thus may play some protective role against endogenous oxidative tissue damage in the brain (Baez et al., 1997). The soluble forms exist as dimeric proteins, with subunit molecular weights of approximately 25 kDa (Table 1). Each subunit of the dimeric enzyme has an active site composed of 2 distinct functional regions: a hydrophilic G-site, which binds the physiological substrate glutathione, and an adjacent H-site which provides a hydrophobic environment for the binding of structurally diverse electrophilic substrates (Armstrong, 1997). The G-site is highly conserved between all GSTs due to its high specificity for GSH, whereas the H-site can be quite divergent between different GSTs, and exhibits broad and variable substrate binding specificity.
Effects of Ammonia Inhalation and Acetic Acid Pretreatment on Colonization Kinetics of Toxigenic Pasteurella multocida within Upper Respiratory Tracts of Swine

ABSTRACT Pigs reared in intensive production systems are continuously exposed to ammonia released by the microbial degradation of their excrement. Exposure to this gas has been shown to increase the severity of the disease progressive atrophic rhinitis by facilitating colonization of the pig’s upper respiratory tract by Pasteurella multocida. The etiological mechanism responsible for this synergy was investigated by studying the colonization kinetics of P. multocida enhanced by ammonia and comparing them with those evoked by an established disease model. Three-week-old Large White piglets were weaned and allocated to five experimental groups (groups A to E). Pigs in groups A and B were exposed continuously to ammonia at 20 ppm for the first 2 weeks of the study. Pigs in group C were pretreated with 0.5 ml of 1% acetic acid per nostril on days −2 and −1 of the study. On day 0 all the pigs in groups A, C, and D were inoculated with 1.4 × 108 toxigenic P. multocida organisms given by the intranasal route. The kinetics of P. multocida colonization were established by testing samples obtained at weekly intervals throughout the study. The study was terminated on day 37, and the extent of turbinate atrophy was determined by using a morphometric index. The results of the study showed that exposure to aerial ammonia for a limited period had a marked effect on the colonization of toxigenic P. multocidain the nasal cavities of pigs, which resulted in the almost total exclusion of commensal flora. In contrast, ammonia had only a limited effect on P. multocida colonization at the tonsil. The exacerbation of P. multocida colonization by ammonia was restricted to the period of ammonia exposure, and the number ofP. multocida organisms colonizing the upper respiratory tract declined rapidly upon the cessation of exposure to ammonia. During the exposure period, the ammonia levels in mucus recovered from the nasal cavity and tonsil were found to be 7- and 3.5-fold higher, respectively, than the levels in samples taken from unexposed controls. Acetic acid pretreatment also induced marked colonization of the nasal cavity which, in contrast to that induced by ammonia, persisted throughout the time course of the study. Furthermore, acetic acid pretreatment induced marked but transient colonization of the tonsil. These findings suggest that the synergistic effect of ammonia acts through an etiological mechanism different from that evoked by acetic acid pretreatment. A strong correlation was found between the numbers of P. multocida organisms isolated from the nasal cavity and the severity of clinical lesions, as determined by using a morphometric index. The data presented in the paper highlight the potential importance of ammonia as an exacerbating factor in respiratory disease of intensively reared livestock.
Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology

Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s diseases (HD). We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.
LED Lighting System Switched-Mode Power Supply

Methods for achieving high efficiency are studied for 15 W SMPS using flyback converter. Transformer in sandwich form is used to reduce leakage current. MOSFETs with low on-resistance are used to reduce energy loss. Schottky diode is used for output. Condenser with low internal equivalent series resistance is used as an output electrolytic condenser. This SMPS shows efficiency of 83.1% at 220 Vac input and 1.2A output current.
Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb

Pheromones from urine of unfamiliar conspecific male animals can reinitiate a female's estrus cycle to cause pregnancy block through the vomeronasal organ (VNO)‐accessory olfactory bulb (AOB)‐hypothalamic pathway. This phenomenon is called the Bruce effect. Pheromones from the mate of the female, however, do not trigger re‐entrance of the estrus cycle because an olfactory memory toward its mate is formed. The activity of the VNO‐AOB‐hypothalamic pathway is negatively modulated by GABAergic granule cells in the AOB. Since these cells are constantly replenished by neural stem cells in the subventricular zone (SVZ) of the lateral ventricle throughout adulthood and adult neurogenesis is required for mate recognition and fertility, we tested the hypothesis that pheromones from familiar and unfamiliar males may have different effects on adult AOB neurogenesis in female mice. When female mice were exposed to bedding used by a male or lived with one, cell proliferation and neuroblast production in the SVZ were increased. Furthermore, survival of newly generated cells in the AOB was enhanced. This survival effect was transient and mediated by norepinephrine. Interestingly, male bedding‐induced newborn cell survival in the AOB but not cell proliferation in the SVZ was attenuated when females were subjected to bedding from an unfamiliar male. Our results indicate that male pheromones from familiar and unfamiliar males exert different effects on neurogenesis in the adult female AOB. Given that adult neurogenesis is required for reproductive behaviors, these divergent pheromonal effects may provide a mechanism for the Bruce effect. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 632–645, 2013
Health Care Utilization for Low Back Pain in Belgium: Influence of Sociocultural Factors and Health Beliefs

Study Design. A population-based survey was undertaken. Objectives. To describe health care utilization for low back pain (LBP) in a culturally diverse society with universal access to health care; to describe how LBP chronicity influences health care utilization; and to describe how sociocultural and demographic factors and health beliefs influence health care utilization. Methods. A probability sample of approximately 5,000 Belgian adults stratified by gender, age, social class, and habitat was surveyed by trained interviewers. Information on demographics, health beliefs, frequency of LBP, and health care utilization was elicited. Statistical analysis was conducted by means of univariate and multivariate logistic regression. Analysis was restricted to 2,660 respondents with history of LBP. Results. Of subjects with LBP, 38% reported daily LBP. Sixty-three percent had seen a health professional for the most recent episode; 11% had been on bed rest. Forty-four percent had at sometime undergone radiography; three and a half percent had ever undergone spinal surgery. Eighty-six percent considered themselves in good health. Controlling for LBP frequency, all forms of health care utilization examined were associated with health beliefs. Conclusions. LBP frequency, health beliefs, and sociocultural factors influence health care behaviors and utilization among adults with a history of LBP in a society with universal access to health care. The association of history of spinal surgery with reports of daily LBP suggests that spinal surgery has failed, at least partly, to relieve LBP.
What Ails the European Union's Emissions Trading System? Two Diagnoses Calling for Different Treatments

In theory, how a fixed number of storable pollution permits are allocated in a cap-and-trade trade program should not affect intertemporal prices unless participants fail to receive permit endowments before they plan to use them. "Backloading" can create inefficiency; "frontloading" cannot. The European Union's Emissions Trading System, however, is regarded as a counterexample where frontloading itself is creating inefficiency. This view underlies current policy proposals to backload permits or to create a Market Stability Reserve. The goal of these policies is to shrink the current inventory of permits carried by the private sector without tightening the cap. We question the most prominent theory of why frontloading has been excessive by comparing its implications to a theory that attributes recent movements in the spot price of permits to ongoing regulatory risk of a price collapse much like what occurred in the 1970's in anticipation of the devaluation of the Mexican peso or the sale of massive government gold stockpiles. Correct diagnosis should precede treatment advice: if frontloading is excessive, inefficiency can be eliminated by suitable backloading of permits; if regulatory risk is excessive, however, backloading either directly or with a market stability reserve is unlikely to reduce inefficiency.
[Determinants of paroxysmal atrial fibrillation in patients with arterial hypertension].

INTRODUCTION Atrial fibrillation represents an important arrhythmia, in particular in patients with arterial hypertension. Hitherto, the connection between paroxysmal atrial fibrillation, left atrial size and left ventricular muscle mass has not been investigated sufficiently. In the present study, determinants of paroxysmal atrial fibrillation in patients with arterial hypertension were evaluated. METHODS 104 consecutive patients were enrolled into this study. All of them suffered from arterial hypertension for more than one year. Persistent or permanent atrial fibrillation was not documented. In all of these patients, clinical, echocardiographic and rhythmologic variables were evaluated. RESULTS In 10.3% of the patients, paroxysmal atrial fibrillation was found. These patients showed a significantly larger left atrium (43.3 +/- 6.7 vs 37.5 +/- 4.9 mm, p < 0.001), a significantly higher muscle mass of the left ventricle (152.38 +/- 43.57 vs 134.41 +/- 27.19 g/m2, p < 0.01) and significantly more frequent a mild mitral regurgitation (38.1 vs 28.6%, p < 0.01). The multivariate regression analysis revealed as independent factors for paroxysmal atrial fibrillation the size of the left atrium and the presence of mild mitral regurgitation. Independent factors for an enlarged left atrium were mitral insufficiency and left ventricular muscle mass. CONCLUSION This study shows that paroxysmal atrial fibrillation in aterial hypertension is based on the left atrial size, and left atrial size on left ventricular muscle mass. Therefore, these results should lead to a causal therapy for treatment of paroxysmal atrial fibrillation in these patients.
The chemokine receptor switch paradigm and dendritic cell migration: its significance in tumor tissues

Localization in tissues and migration to lymphoid organs are essential steps in the immunobiology of dendritic cells (DC). Chemokines play an important role in guiding the traffic of DC. Receptor expression and responsiveness to constitutively made chemokines account for the presence of DC in normal tissues. Inflammatory chemokines and non-chemokine attractants promote recruitment and localization of DC at sites of inflammation and infection. During maturation, DC undergo a profound and orderly rearrangement of their chemokine receptor repertoire. The chemokine receptor switch paradigm provides a conceptual framework for the complex migration of DC in vivo, including their recruitment and positioning in tumor tissues.
SMES/Battery Hybrid Energy Storage System for Electric Buses

This paper proposes a novel use of superconducting magnetic energy storage (SMES) hybridized with the battery into the electric bus (EB) with the benefit of extending battery lifetime. A new power control algorithm, which integrates a power grading strategy with the filtration control method, is introduced in this paper, achieving further improvement of battery lifetime. To demonstrate the performance of the SMES/battery hybrid energy storage system (HESS), a dynamic EB system is described with the advantage of considering more factors into the driving patterns. Simulation results show that the proposed HESS has successfully combined the SMES with the battery forming an optimal system that has the advantages of primary energy storage systems while complementing the disadvantages of each system. This paper also does the quantitative analysis of battery lifetime extension in the battery-only system, the filtration-based HESS, and the novel control-based HESS.
The Day-of-the-Week Effect: Anomaly or Illusion? New Evidence from Sri Lanka’

In this paper the Day-of-the-Week effect is studied by comparing the empirical cumulative distribution functions (ECDFs) of the close-to-close log-returns of one day-of-the-week to the remaining weekday log-returns amongst the stocks comprising the S&P Sri Lanka 20 Index for the period January 2006 to December 2012. The sample period for the study is sub-divided into two periods: the civil war period (1st January 2006 to 18th May 2009) and the post civil war period (19th May 2009 to 31st December 2012). A modified Kolmogorov-Smirnov statistic, called the DoW-statistic, was then used to define the degree of DoW efficiency. The DoW-statistic for each stock is subsequently used to rank the S&P Sri Lanka 20 Index stocks according to their DoW efficiencies. The classical Kolmogorov-Smirnov test is then used to ascertain the statistical significance of these DoW statistics. With no adjustments for ARCH effects, the results indicate that DoW effects were weak during the war period but strong during the post-war period. However, when potential ARCH effects were taken into account, both periods showed evidence of strong DoW effects, indicating the Day-of-the-Week effect to be an anomaly rather than an illusion.
Hepatic expression of ABC transporters G5 and G8 does not correlate with biliary cholesterol secretion in liver transplant patients

The adenosine triphosphate (ATP)‐binding cassette (ABC)‐transporters ABCG5 and ABCG8 have been shown to mediate hepatic and intestinal excretion of cholesterol. In various (genetically modified) murine models, a strong relationship was found between hepatic expression of ABCG5/ABCG8 and biliary cholesterol content. Our study aimed to relate levels of hepatic expression of ABCG5 and ABCG8 to biliary excretion of cholesterol in man. From 24 patients who had received a liver transplant, bile samples were collected daily after transplantation over a 2‐week period to determine biliary composition. Expression of ABCG5, ABCG8, MDR3, and BSEP was assessed by real‐time polymerase chain reaction (PCR) in liver biopsy specimens collected before and after transplantation. Levels of hepatic ABCG5, ABCG8, and MDR3 messenger RNA (mRNA) were strongly correlated. After transplantation, the biliary secretion rate of cholesterol continuously increased, coinciding with gradual increases in bile salt and phospholipid secretion. In contrast, hepatic levels of ABCG5 and ABCG8 mRNA remained unchanged. Surprisingly, no correlation was found between the hepatic expression of ABCG5 and ABCG8 and rates of biliary cholesterol secretion, normalized for biliary phospholipid secretion. As expected, the concentration of biliary phospholipids correlated well with MDR3 expression. In conclusion, the strong relationship between ABCG5 and ABCG8 gene expression is consistent with the coordinate regulation of both genes, and in line with heterodimerization of both proteins into a functional transporter. Hepatic ABCG5/ABCG8 expression, at least during the early phase after transplantation, is not directly related to biliary cholesterol secretion in humans. This finding suggests the existence of alternative pathways for the hepatobiliary transport of cholesterol that are not controlled by ABCG5/ABCG8. (HEPATOLOGY 2005;42:1166–1174.)
Hsp70 overexpression inhibits NF‐κB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy

Heat shock protein 70 (Hsp70) is a highly conserved and ubiquitous protein that is reported to provide cytoprotection in various cell types and tissues. However, the importance of Hsp70 expression during skeletal muscle atrophy, when Hsp70 levels are significantly decreased, is not known. The current study aimed to determine whether plasmid‐mediated overexpression of Hsp70, in the soleus muscle of rats, was sufficient to regulate specific atrophy signaling pathways and attenuate skeletal muscle disuse atrophy. We found that Hsp70 overexpression prevented disuse muscle fiber atrophy and inhibited the increased promoter activities of atrogin‐1 and MuRF1. Importantly, the transcriptional activities of Foxo3a and NF‐κB, which are implicated in the regulation of atrogin‐1 and MuRF1, were abolished by Hsp70. These data suggest that Hsp70 may regulate key atrophy genes through inhibiting Foxo3a and NF‐κB activities during disuse. Indeed, we show that specific inhibition of Foxo3a prevented the increases in both atrogin‐1 and MuRF1 promoter activities during disuse. However, inhibition of NF‐κB did not affect the activation of either promoter, suggesting its requirement for disuse atrophy is through its regulation of other atrophy genes. We conclude that overexpression of Hsp70 is sufficient to inhibit key atrophy signaling pathways and prevent skeletal muscle atrophy. — Senf, S. M. , Dodd, S. L. , McClung, J. M. , Judge, A. R. Hsp70 overexpression inhibits NF‐κB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J. 22, 3836–3845 (2008)
Domain-specific knowledge as playful interaction: the case of Prime Slaughter

Starting from reflections on designing games for learning, aimed at providing a tangible grounding to abstract knowledge, we designed Prime Slaughter, a game to support learning of factorisation and prime numbers, targeted to primary and early secondary school children. This new study draws upon the design process of Prime Slaughter, to move further in developing a general approach in developing games, aimed at effectively conveying knowledge from a specific domain. Hence, this paper will discuss the past design process, as a concrete case, and then formulate a theoretical framework, based on activity theory, aimed at facilitating the transposition of abstract knowledge into playful interactions, so to develop new learning games of this kind, also keeping into account children's individual needs regarding play.