Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential biallelic activation of three insulin-like growth factor II promoters in the mouse central nervous system.

Imprinting of the insulin-like growth factor II gene (IGF-II) is conserved in human, rat, and mouse. In human liver and chondrocytes, IGF-II transcripts from promoter hP1 are always derived from both parental alleles, while transcripts from promoters hP2-hP4 are from one parental allele. To examine the promoter-specific imprinting pattern of mouse IGF-II, we examined IGF-II expression in F1 generation mice derived from crossing M. spretus with M. musculus using a novel BsaA1 polymorphism in mouse IGF-II exon 6. There was maintenance of maternal IGF-II imprinting in all non-central nervous system (CNS) tissues in the F1 generation animals. However, there was biallelic expression of the IGF-II gene in CNS. Allelic expression of each IGF-II promoter transcript was examined by full-length cDNA amplification with promoter-specific primers. In every tissue in which IGF-II was imprinted, IGF-II transcripts were derived from paternal promoters mP1-mP3, while the maternal allele was suppressed. In the CNS, however, promoters mP1-mP3 of the imprinted maternal allele became activated, leading to the biallelic expression of IGF-II. Moreover, the expression of IGF-II from each parental allele differed in various CNS regions. In leptomeninges, mP1-mP3 drive IGF-II expression predominantly from the paternal allele, while in some CNS regions, the promoter transcripts were primarily from the maternal allele. The coordinate regulation of mouse IGF-II promoters suggests the presence of an upstream imprinting complex controlling IGF-II imprinting. (ABSTRACT TRUNCATED AT 250 WORDS)
An economic evaluation of intravenous versus oral iron supplementation in people on haemodialysis.

BACKGROUND Iron supplementation can be administered either intravenously or orally in patients with chronic kidney disease (CKD) and iron deficiency anaemia, but practice varies widely. The aim of this study was to estimate the health care costs and benefits of parenteral iron compared with oral iron in haemodialysis patients receiving erythropoiesis-stimulating agents (ESAs). METHODS Using broad health care funder perspective, a probabilistic Markov model was constructed to compare the cost-effectiveness and cost-utility of parenteral iron therapy versus oral iron for the management of haemodialysis patients with relative iron deficiency. A series of one-way, multi-way and probabilistic sensitivity analyses were conducted to assess the robustness of the model structure and the extent in which the model's assumptions were sensitive to the uncertainties within the input variables. RESULTS Compared with oral iron, the incremental cost-effectiveness ratios (ICERs) for parenteral iron were $74,760 per life year saved and $34,660 per quality-adjusted life year (QALY) gained. A series of one-way sensitivity analyses show that the ICER is most sensitive to the probability of achieving haemoglobin (Hb) targets using supplemental iron with a consequential decrease in the standard ESA doses and the relative increased risk in all-cause mortality associated with low Hb levels (Hb < 9.0 g/dL). If the willingness-to-pay threshold was set at $50,000/QALY, the proportions of simulations that showed parenteral iron was cost-effective compared with oral iron were over 90%. CONCLUSIONS Assuming that there is an overall increased mortality risk associated with very low Hb level (<9.0 g/dL), using parenteral iron to achieve an Hb target between 9.5 and 12 g/L is cost-effective compared with oral iron therapy among haemodialysis patients with relative iron deficiency.
Semi‐quantitative assessment of disease risks at the human, livestock, wildlife interface for the Republic of Korea using a nationwide survey of experts: A model for other countries

Wildlife-associated diseases and pathogens have increased in importance; however, management of a large number of diseases and diversity of hosts is prohibitively expensive. Thus, the determination of priority wildlife pathogens and risk factors for disease emergence is warranted. We used an online questionnaire survey to assess release and exposure risks, and consequences of wildlife-associated diseases and pathogens in the Republic of Korea (ROK). We also surveyed opinions on pathways for disease exposure, and risk factors for disease emergence and spread. For the assessment of risk, we employed a two-tiered, statistical K-means clustering algorithm to group diseases into three levels (high, medium and low) of perceived risk based on release and exposure risks, societal consequences and the level of uncertainty of the experts' opinions. To examine the experts' perceived risk of routes of introduction of pathogens and disease amplification and spread, we used a Bayesian, multivariate normal order-statistics model. Six diseases or pathogens, including four livestock and two wildlife diseases, were identified as having high risk with low uncertainty. Similarly, 13 diseases were characterized as having high risk with medium uncertainty with three of these attributed to livestock, six associated with human disease, and the remainder having the potential to affect human, livestock and wildlife (i.e., One Health). Lastly, four diseases were described as high risk with high certainty, and were associated solely with fish diseases. Experts identified migration of wildlife, international human movement and illegal importation of wildlife as the three routes posing the greatest risk of pathogen introduction into ROK. Proximity of humans, livestock and wildlife was the most significant risk factor for promoting the spread of wildlife-associated diseases and pathogens, followed by high density of livestock populations, habitat loss and environmental degradation, and climate change. This study provides useful information to decision makers responsible for allocating resources to address disease risks. This approach provided a rapid, cost-effective method of risk assessment of wildlife-associated diseases and pathogens for which the published literature is sparse.
Price transmission and market integration: vertical and horizontal price linkages for salmon

Relationships between prices are of interest when testing for market integration as well as analyses of supply chains. A feature that has received little attention is that if two supply chains are linked by market integration at some stage, then the whole supply chain will be linked. Furthermore, the leading price in such a system can be in one supply chain and will not be revealed in market integration studies or analysis of a single supply chain. An empirical analysis is provided for the supply chains for salmon which originates in Norway and the United Kingdom and is then sold at retail level in France as smoked salmon. We find a high degree of price transmission in both supply chains, as well as integrated markets.
Transcription start sites downstream of the Epstein-Barr virus (EBV) Fp promoter in early-passage Burkitt lymphoma cells define a fourth promoter for expression of the EBV EBNA-1 protein

In Epstein-Barr virus (EBV)-transformed B lymphoblastoid and many Burkitt lymphoma cell lines, the EBV EBNA-1 protein is one of six viral nuclear antigens expressed from a common transcription unit under the control of one of two promoters, Wp or Cp. In contrast, EBNA-1 is the only EBV nuclear antigen expressed in Burkitt and other EBV-positive tumors. We previously identified a promoter of EBNA-1 transcription, designated Fp, in early-passage Mutu Burkitt tumor cells, and this promoter is also active in long-term Mutu and Akata Burkitt cell lines which maintain the exclusive expression of EBNA-1 characteristic of the tumor. However, transcription initiation within Fp reporter gene plasmids in EBV-negative cells occurs at positions 100 to 200 bases downstream of the Fp start site in the BamHI-Q restriction fragment. Here we demonstrate that transcription initiation within newly established Burkitt lymphoma cell lines is consistent with the transcription initiation we observed in reporter plasmids. Furthermore, previous observations of transcription from Fp to generate EBNA-1 transcripts can be attributed to lytic-cycle gene expression. These data, in conjunction with our previous characterization of promoter regulatory elements, define a fourth EBNA-1 promoter, Qp, that is active in latently infected Burkitt tumor cells.
Construction and Characterization of an Attenuated Listeria monocytogenes Strain for Clinical Use in Cancer Immunotherapy

ABSTRACT Listeria monocytogenes has been exploited previously as a vaccine vector for the delivery of heterologous proteins such as tumor-specific antigens for active cancer immunotherapy. However, for effective use of live vector in clinics, safety is a major concern. In the present study, we describe an irreversibly attenuated and highly immunogenic L. monocytogenes platform, the L. monocytogenes dal-, dat-, and actA-deleted strain that expresses the human prostate-specific antigen (PSA) using an antibiotic resistance marker-free plasmid (the dal dat ΔactA 142 strain expressing PSA). Despite limited in vivo survival, the dal dat ΔactA 142 strain was able to elicit efficient immune responses required for tumor clearance. Our results showed that immunization of mice with the dal dat ΔactA 142 strain caused the regression of the tumors established by the prostate adenocarcinoma cell line expressing PSA. An evaluation of immunologic potency indicated that the dal dat ΔactA 142 strain elicits a high frequency of PSA-specific immune responses. Interestingly, immunization with the dal dat ΔactA 142 strain induced significant infiltration of PSA-specific T cells in the intratumoral milieu. Collectively, our data suggest that the dal dat ΔactA 142 strain is a safe and potent vector for clinical use and that this platform may be further exploited as a potential candidate to express other single or multiple antigens for cancer immunotherapy.
The Evolution of Interaction Shape in Differential Susceptibility

Expectations about the shape of statistical interactions play a crucial role in the study of differential susceptibility and other types of person–environment interplay. These expectations shape methodological guidelines and inform the interpretation of empirical findings; however, their logic has never been explicitly examined. This study is the first systematic exploration of the evolution of interaction shape in differential susceptibility. The model introduced here yields a number of novel insights; for example, interactions in differential susceptibility should usually be asymmetric and likely to be biased toward the prototypical shape of diathesis–stress models. This article also presents an exploratory analysis of interaction shape in recent empirical studies and ends with a discussion of the theoretical and methodological implications of the present findings.
Economic Incentives for Firms to Implement Enhanced Food Safety Controls: Case of the Canadian Red Meat and Poultry Processing Sector

This study assesses quantitatively the economic incentives for firms to adopt food safety controls and the potential impact of a number of firm- and market-specific characteristics on this behavior, focusing on the red meat and poultry processing sector in Canada. The results suggest that market-based (private) incentives have a greater impact on the food safety responsiveness of firms in this sector than government regulatory actions. This creates challenges for regulators in defining policy instruments that promote greater levels of food safety control in food processing sectors rather than constraining firms from taking initiatives that exceed regulatory requirements.
A Novel Nanoparticle Formulation for Sustained Paclitaxel Delivery

PurposeTo develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel.MethodsChitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). ResultsThese studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC50 of PTX.ConclusionThese advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.
Is Prior Director Experience Valuable?

Previous studies have investigated the effectiveness of directors in performing their monitoring and advising functions by examining characteristics such as independence, qualifications and professional expertise. In this study, we propose a more direct measure of director effectiveness – prior experience as a director. Using hand-collected data from Australia, we find that both the depth (number of prior years) and breadth (number of current directorships) of a new appointee’s director experience is valued by shareholders at appointment. In particular, the market reaction is highest for appointees with the most prior director experience (two or more other current directorships in listed companies and four or more years of director experience) and when experienced appointees join less-experienced boards.
A reference profile ontology for communities of practice

Communities of Practice (CoP) integrate people in a group in order to learn in a collaborative way. It is necessary to establish in these communities a formal and standardised representation of the knowledge and interests that emerge from CoP. With this scenario in mind, this paper presents a reference ontology for a user profile representation in a CoP Framework (CoPF). The main idea of this framework is to provide virtual CoP for collaborative learning by using semantic web technologies. This work proposes a foundational ontology for a general profile to be used as a guideline to build a computational CoPF, which is semantic web compliant. In this paper we summarise a first proposition of the CoPF ontology development focusing on the ontological user profile. We also present the methodological aspects of the ontological CoPF and also illustrate a case study applying the ontological user profile.
A novel hepatitis B virus X‐interactive protein: Cytochrome C oxidase III

Background: Hepatitis B virus‐encoded X protein has been shown to be capable of activating many different viral and cellular promoters through protein–protein interactions and to contribute to the development of hepatocellular carcinoma. As its mechanism has not yet been identified unequivocally, the aim of the present study was to screen the cellular proteins that can interact with X protein.
Teaching Software Synthesis Through Csound's New Modelling Opcodes

The computational power of today's computers brings the most powerful signal processing and synthesis tools into the home studio. For less than $2000 you can have the equivalent of the IRCAM ISPW or a NeXT running “SynthBuilder” on your battery powered PPC or PC Laptop, and all the “essential” software tools and utilities can be had commercially at low cost or are freely available over the Internet. Thus we are seeing that independent composers and freelance artists are seeking out this software, and placing demands on the designers for ease of use and general utility. This paper concentrates on one of the remaining problems which limits the widespread use of the technology, and that is the complexity in specifying every feature of a composition, and in particular describing the detailed timbral evolution of each note. We explore the new facilities in Csound which address this problem.
Dissociable Roles of the Superior Temporal Sulcus and the Intraparietal Sulcus in Joint Attention: A Functional Magnetic Resonance Imaging Study

Previous imaging work has shown that the superior temporal sulcus (STS) region and the intraparietal sulcus (IPS) are specifically activated during the passive observation of shifts in eye gaze [Pelphrey, K. A. , Singerman, J. D. , Allison, T. , & McCarthy, G. Brain activation evoked by perception of gaze shifts: The influence of context. Neuropsychologia, 41, 156170, 2003; Hoffman, E. A. , & Haxby, J. V. Distinct representations of eye gaze and identity in the distributed human neural system for face perception. Nature Neuroscience, 3, 8084, 2000; Puce, A. , Allison, T. , Bentin, S. , Gore, J. C. , & McCarthy, G. Temporal cortex activation in humans viewing eye and mouth movements. Journal of Neuroscience, 18, 21882199, 1998; Wicker, B. , Michel, F. , Henaff, M. A. , & Decety, J. Brain regions involved in the perception of gaze: A PET study. Neuroimage, 8, 221227, 1998]. Are the same brain regions also involved in extracting gaze direction in order to establish joint attention? In an event-related functional magnetic resonance imaging experiment, healthy human subjects actively followed the directional cue provided by the eyes of another person toward an object in space or, in the control condition, used a nondirectional symbolic cue to make an eye movement toward an object in space. Our results show that the posterior part of the STS region and the cuneus are specifically involved in extracting and using detailed directional information from the eyes of another person to redirect one's own gaze and establish joint attention. The IPS, on the other hand, seems to be involved in encoding spatial direction and mediating shifts of spatial attention independent of the type of cue that triggers this process.
Management Development in Small and Medium‐sized Enterprises in Newfoundland and Labrador

Memorial University of Newfoundland, based in St. John's, is the single university in the Province of Newfoundland and Labrador. The Faculty of Business Administration is the largest concentration of resident business educational and management development expertise. In 1980, the Faculty established the Center for Management Development with the role to coordinate its non‐credit, continuing professional business educational and management training and development activities. The mandate of the Center is the development and delivery of continuing entrepreneurship and business management education programmes for the public, and for practising managers in business, government and other organisations in the province — it is to develop management in Newfoundland and Labrador. As part of the Faculty of Business Administration, the Center exists to provide management development offerings where they are most needed, and not solely on the basis of commercial profitability.
From Unemployment Benefits to Unemployment Accounts

We explore the implications of replacing current unemployment benefit (UB) systems by unemployment accounts (UA). Under the UA system, employed people would be required to make ongoing contributions to their unemployment accounts, and the balances in these accounts would then be available to them during periods of unemployment. The government would be able to undertake balanced-budget redistributions among the UAs, taxing the contributions of the rich and subsidizing those of the poor. When people retire, they could use their remaining UA balances to top up their pensions. Under the unemployment benefit system, people are in effect rewarded for being unemployed (through the unemployment benefits) and penalized for being employed (through the taxes that finance the unemployment benefits). The UA system alleviates these externality problems. For when an unemployed person makes withdrawals from his UA, he is thereby diminishing the amount of funds that are available to him later on.
Neural control of counter-regulatory events during glucopenia in man.

The effect of autonomic denervation on the metabolic and hormonal responses during intracellular glucopenia in man was investigated. 2-Deoxy-d-glucose (2 DG), a competitive inhibitor of glucose metabolism, was administered intravenously to nine normal volunteers and to five patients, three with complete cervical cord transection (C-6) and two with idiopathic orthostatic hypotension. Before, during, and after a 20 min infusion of 2 DG (50 mg/kg) plasma concentrations of glucose, lactate, FFA, total catecholamines, immunoreactive insulin (IRI), human growth hormone (HGH), and cortisol were determined for periods up to 150 min. In control subjects, the initial elevation of FFA, glucose. HGH, and cortisol corresponded with the rise in total catecholamines, with maximal levels attained at 60 min, lactate rose at a slower rate, reaching peak levels at 150 min: although no change in IRI was noted. In contrast, 2 DG-induced glucopenic stress in the autonomic denervated subjects was characterized by no detectable catecholamine release or significant rise in glucose, FFA, lactate, or IRI. However, HGH and cortisol responses in four of the five patients were of a similar or greater magnitude than controls.These studies demonstrate that the integrity of the sympathoadrenomedullary axis is essential for the counter-regulatory response to intracellular glucopenia in man. Cortisol and HGH have no apparent role in these events.
Impact of Calendar Life and Cycling Ageing on Supercapacitor Performance

Supercapacitors (SCs), which are also known as ultracapacitors, are commonly based on porous activated carbon electrodes and electrostatic charge-storage mechanisms. Carbon electrodes are supposed to be chemically and electrochemically inert, and the electrostatic nature of the charge-storage mechanism is highly reversible. These properties should assure that SCs have an infinite shelf life. However, in practice, SC cells exhibit performance fading when they are used for months. The purpose of this paper is to compare the performance fading of SCs in two types of tests. The first accelerated test is the calendar life test, which evaluates cell degradation when cells are used at elevated voltages and temperatures; these degradations are observed in cells during rest periods. The second test is the power cycling test, which corresponds to degradations during the actual use of SCs as peak power sources in hybrid electric applications. In this paper, we use an impedance model to monitor changes in cell behavior. This analytical impedance model is based not only on physical quantities, such as double-layer capacitance, specific area, and electrolyte conductivity, but on elementary electrode dispersion as well. This model is validated in the frequency domain using the initial state of the tested SC for different temperature and voltage configurations. Then, we present and specify two types of tests. A periodic characterization based on impedance spectroscopy is done to quantify impedance changes during the ageing tests. The obtained results confirm that the impedance real part is increasing and that the capacitance is decreasing during the two ageing tests; however, the way they change is different. Indeed, the shape of the impedance real part is conserved in the calendar life test, whereas it is distorted in the power cycling test. This difference will be explained in terms of the evolution of the impedance model parameters. This paper confirms that the two ageing tests affect the SC performances differently.