Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of P-Glycoprotein in the Disposition of Macrocyclic Lactones: A Comparison between Ivermectin, Eprinomectin, and Moxidectin in Mice

Macrocyclic lactones (MLs) are lipophilic anthelmintics and substrates for P-glycoprotein (P-gp), an ATP-binding cassette transporter involved in drug efflux out of both host and parasites. To evaluate the contribution of P-gp to the in vivo kinetic disposition of MLs, the plasma kinetics, brain concentration, and intestinal excretion of three structurally different MLs (ivermectin, eprinomectin, and moxidectin) were compared in wild-type and P-gp-deficient [mdr1ab(−/−)] mice. Each drug (0.2 mg/kg) was administered orally, intravenously, or subcutaneously to the mice. Plasma, brain, and intestinal tissue concentrations were measured by high-performance liquid chromatography. The intestinal excretion rate after intravenous administration was determined at different levels of the small intestine by using an in situ intestinal perfusion model. P-gp deficiency led to a significant increase in the area under the plasma concentration-time curve (AUC) of ivermectin (1.5-fold) and eprinomectin (3.3-fold), whereas the moxidectin AUC was unchanged. Ivermectin and to a greater extent eprinomectin were both excreted by the intestine via a P-gp-dependent pathway, whereas moxidectin excretion was weaker and mostly P-gp-independent. The three drugs accumulated in the brains of the mdr1ab(−/−) mice, but eprinomectin concentrations were significantly lower. We concluded that eprinomectin disposition in mice is controlled mainly by P-gp efflux, more so than that of ivermectin, whereas moxidectin disposition appears to be mostly P-gp-independent. Given that eprinomectin and ivermectin have higher affinity for P-gp than moxidectin, these findings demonstrated that the relative affinity of MLs for P-gp could be predictive of the in vivo kinetic behavior of these drugs.
Excitation UNFOLD (XUNFOLD) to improve the temporal resolution of multishot tailored RF pulses

An extension of the “UNaliasing by Fourier encoding the Overlaps using the temporaL Dimension” (UNFOLD) method to the excitation domain (XUNFOLD) is presented to improve the temporal resolution of multishot tailored RF (TRF) pulses. Multishot three‐dimensional TRF pulses were designed to produce a time series of images with periodically aliased excitation profiles. The XUNFOLD method is shown to remove the excitation profile aliasing from the dynamic imaging data by filtering in the temporal frequency dimension. The technique is demonstrated to improve the temporal resolution of simulated functional MRI (fMRI) activation in a time series of brain images. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Intrinsically switchable thin film ferroelectric resonators

This paper presents DC voltage dependent thin film bulk acoustic wave resonators (FBARs) based on ferroelectric barium strontium titanate (BST). The electrostrictive effect in BST film that enables the resonances to switch on and off with dc bias is discussed. Composite BST FBARs that consist of BST, platinum (Pt), silicon (Si), and oxide (SiO2) layers are discussed by comparing with the conventional FBAR structure. For composite FBARs, the BST layer is primarily used for transduction while the Si and SiO2 layers are used to increase the overall quality factor (Q). Measurement results of a composite FBAR show a Q that exceeds 600 at its parallel resonance frequency of 2.169 GHz and an electromechanical coupling coefficient of 0.68%.
Analysis of Mitochondrial DNA From the Teeth of a Cadaver Maintained in Formaldehyde

This was a case that brought great commotion to a university in the interior of Brazil since it was suspected that one of the human bodies used for teaching anatomy was a relative of one of the students. Analysis of fragments of hypervariable region 2 of mitochondrial DNA (mtDNA) was performed using a miniprimer set (MPS), indicating that there had been a mistake in evaluation by the student, reinforcing the need to base the process of human identification in technical parameters.
Platelet‐Derived Growth Factor BB Secreted From Osteoclasts Acts as an Osteoblastogenesis Inhibitory Factor

Osteoclasts and osteoblasts are responsible for strict bone maintenance with a balance between bone formation and resorption by interacting with each other. Recently, it has been revealed that osteoblasts/stromal cells regulate differentiation of osteoclasts/hematopoietic cells by two factors, the receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL) on the plasma membrane, and secreted osteoprotegerin (OPG). However, no factors have yet been reported by which osteoclasts/hematopoietic cells regulate osteoblasts/stromal cells. To elucidate the possibility of signal transduction from osteoclasts to osteoblasts, we studied the conditioned medium of mouse osteoclast‐like myeloma cell line RAW264.7 treated with RANKL. We found that this medium contains a factor that inhibits differentiation of mouse osteoblast precursor‐like cell line MC3T3‐E1 to osteoblasts induced by bone morphogenetic protein 4 (BMP‐4) and named this factor osteoblastogenesis inhibitory factor (OBIF). OBIF was purified by successive three‐step chromatography by heparin affinity, anion exchange, and reversed‐phase columns. Osteoblastogenesis inhibitory activity made one peak in each chromatography step, showing the factor is a single entity. Active fractions were loaded on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and bands of proteins were excised, digested by trypsin, and analyzed by liquid chromatography equipped with tandem mass spectrometry (LC/MS/MS). Consequently, we have identified this factor to be platelet‐derived growth factor BB (PDGF BB) homodimer. Furthermore, this identification of PDGF BB as OBIF was confirmed by neutralization of the inhibitory activity of the medium with anti‐PDGF antibody. These results show, for the first time, that osteoclasts regulate osteoblasts directly and suggest that PDGF BB is a key factor in bone remodeling.
Modelling of bottom-lit down-draft (BLDD) clean-burning coal stove

The use of coal as a household fuel to meet requirements of cooking and heating in low income communities on the South African Highveld results high levels of indoor and ambient air pollution. The combustion of coal is regarded as the largest source of air pollution in Gauteng Province, in terms of resultant human exposure. As part of measures to combat this problem, an innovative clean-burning multi-use (cooking and heating) coal stove has been developed. Incorporating a bottom-lit down-draft (BLDD) design. However, optimising the fundamental design by construction and testing has been a time and resource consuming exercise. In this paper we report on the use of PHOENICS computational fluid dynamics (CFD) software to develop a model for simulating an optimal geometry for the BLDD coal stove, including heat and gas transfer components. We used mass, momentum and energy balances built within PHOENICS software, through FLAIR program (a special-purpose sub-module program of PHOENICS, designed to provide an air-flow and thermal-simulation facility for heating, ventilation and air conditioning systems), to evaluate the basic design in terms of heat distribution from fuel bed to exhaust pipe. As a simplifying assumption for computational efficiency, a model using rectangular conduits was built and validated by comparing the simulations with experimental performance of the stove. This article reports the initial findings of the CFD modelling, involving air flows and temperature profile, assuming a constant heat source located in the combustion chamber. Validation of the model will lead to an accelerated design cycle for reaching a design solution for optimised thermal (cooking) performance and reduced pollution emissions.
Trade Liberalization, Pollution and Poverty: Evidence from Lao PDR

Various empirical studies have confirmed that trade liberalization stimulates economic growth. In order to strengthen economic development and emerge from Least Developed Country (LDC) status by the year 2020, the Government of Lao (GoL) PDR is eager to capitalize on trade liberalization agreements such as the ASEAN Free Trade Area (AFTA) and future membership of trade organizations such as the World Trade Organization (WTO). However, the exact impact of trade liberalization is debatable, especially in LDCs such as Lao PDR, which face various economic and social constraints. Due to a lack of research on this issue, the impact of trade liberalization on pollution and poverty is unclear from a quantitative perspective. The main objective of this study is to use a Computable General Equilibrium (CGE) model to analyze the impact of trade liberalization on pollution and poverty. In particular, this study uses two approaches: a Global CGE model – GTAP model – to assess the impact of trade liberalization on CO2 emissions, and a micro-simulation to assess the impact of trade liberalization on poverty. The results from the GTAP model show that trade liberalization has a positive effect on growth, but this effect is relatively small. Surprisingly, trade liberalization decreases CO2 emissions but the change is small due mainly to declining output in some sectors as a result of trade liberalization. However, trade liberalization increases the rate of resource depletion in some sectors because the demand for products increases. The micro-simulation using a household survey indicates that the change in household welfare due to tariff reduction is heterogeneous. The winners from the tariff cut are urban households, households in Vientiane, the capital of Lao PDR, and non-poor households in urban areas. The losers from this policy change are households that do not belong to the above categories; these households suffer a drop in income and their poverty rate increases.
Incidences of New Prescribing by British Child and Adolescent Psychiatrists: a Prospective Study Over 12 Months

Little is known about the epidemiology of pharmacotherapy in the treatment of child psychiatric disorder. This study reports on the systematic prospective collection of instances of new prescribing by child and adolescent mental health services serving a population of approximately four million people in North West England. Diagnostic and demographic information regarding new prescribing by child and adolescent mental health services within Greater Manchester and Lancashire was systematically collected prospectively over two 6-month periods between 2000 and 2002. Within the 12 months studied, there were 845 instances of a drug being newly prescribed to a child or adolescent in the treatment of a psychiatric disorder. In total, 48 different drugs were prescribed for 25 different diagnoses. The eight most commonly prescribed drugs were methylphenidate, methylphenidate/placebo trial, paroxetine, fluoxetine, risperidone, imipramine, dexamphetamine and melatonin, accounting for 73% of all prescribing. There was marked variation between services in the amount of prescribing with significant correlation between prescription of stimulants and prescription of selective serotonin reuptake inhibitor antidepressants. Prescription of medications in the treatment of child psychiatric disorder has become a significant part of child and adolescent mental health practice. However, the evidence base underpinning this usage remains limited, and further high quality therapeutic clinical trials are urgently needed.
Influence of the crown-to-implant length ratio on the clinical performance of implants supporting single crown restorations: a cross-sectional retrospective 5-year investigation.

PURPOSE The aim of this study was to investigate the influence of the crown-to-implant length ratio (c/i ratio) on the implant survival, changes of the marginal bone level (MBL) and the occurrence of biological and technical complications. MATERIAL AND METHODS This cross-sectional retrospective study included all patients with implants in the posterior segments supporting single crown restorations with a minimum follow-up of 5 years. All patients were questioned and examined clinically and radiographically. The technical and biological c/i ratio and the MBL were measured on digitized periapical radiographs. The following outcome parameters in relation to the c/i ratio and the co-factors were statistically analyzed: implant survival rate, MBL, occurrence of technical and biological complications. For statistical analysis, regression, correlation and survival analyses were applied (P<0.05). RESULTS Seventy patients (mean age of 50.7 years [range 19.8-76.6 years]) with a total of 100 implants (24 Straumann type, 76 Brånemark type) were included in this study. The mean follow-up period was 6.2 years (range 4.73-11.7 years). Six implants failed during the follow-up period, yielding a cumulative survival rate of 95.8% at 5 years in function. The mean technical c/i ratio was 1.04 (±0.26, range 0.59-2.01). The mean biological c/i ratio was 1.48 (±0.42, range 0.82-3.24). No statistically significant influence of the technical and biological c/i ratio was found on the implant survival, MBL and occurrence of technical and biological complications. When adjusted for the biological c/i ratio, smoking was the only co-factor significantly associated with implant failure and biological complications. CONCLUSION In the present study, the c/i ratio did not influence the clinical performance of implants supporting single crown restorations in the posterior segments of the jaw within the range tested.
Reconstituted Human TPC1 Is a Proton-Permeable Ion Channel and Is Activated by NAADP or Ca2+

Stimuli that increase calcium or NAADP may promote proton release from the endosomes and lysosomes by activating TPC1. Showing a Preference for Protons Protons (H+) and calcium (Ca2+) produce a variety of different effects in cells. One way to determine which channels allow each of these ions to pass is to isolate the proteins and incorporate them into artificial bilayers. With this approach, Pitt et al. found that H+ was the preferred ion that passed through the human two-pore channel 1 (TPC1), which in cells is located in acidic membrane-bound compartments called endosomes and lysosomes. They also identified intracellular signaling messengers that stimulated TPC1 and signals that changed the relative ability of different positively charged ions to flow through the channel. The exact function of the released H+ remains an open question. NAADP potently triggers Ca2+ release from acidic lysosomal and endolysosomal Ca2+ stores. Human two-pore channels (TPC1 and TPC2), which are located on these stores, are involved in this process, but there is controversy over whether TPC1 and TPC2 constitute the Ca2+ release channels. We therefore examined the single-channel properties of human TPC1 after reconstitution into bilayers of controlled composition. We found that TPC1 was permeable not only to Ca2+ but also to monovalent cations and that permeability to protons was the highest (relative permeability sequence: H+ >> K+ > Na+ ≥ Ca2+). NAADP or Ca2+ activated TPC1, and the presence of one of these ligands was required for channel activation. The endolysosome-located lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] had no effect on TPC1 open probability but significantly increased the relative permeability of Na+ to Ca2+ and of H+ to Ca2+. Furthermore, our data showed that, although both TPC1 and TPC2 are stimulated by NAADP, these channels differ in ion selectivity and modulation by Ca2+ and pH. We propose that NAADP triggers H+ release from lysosomes and endolysomes through activation of TPC1, but that the Ca2+-releasing ability of TPC1 will depend on the ionic composition of the acidic stores and may be influenced by other regulators that affect TPC1 ion permeation.
Touch tracking analysis for graphics image acquisition by the visually impaired: Toward understanding graphical image creation by touch-sensing

One of the problems regarding graphics for blind individual is that we have few data on how he (she) acquires graphical information through touching. In this article, we propose a method of tracking the touch point of his (her) fingertip on graphics material using cameras (an analog of eye-tracking) for analyzing the image acquisition process. We exhibit the method on an edge-outlined tactile picture of a flower and show that it yields basic features of the original outlined flower by an experiment relying on a visually impaired subject. As a linked yet remotely material in Section 3.1 we describe our other application of online tactile map in which we have introduced the idea of sharing positional information between touching a tactile picture and looking into a graphical picture using a tracking technology.
Transitional Dynamics and Indeterminacy of Equilibria in an Endogenous Growth Model with a Public Input

The authors analyze an endogenous growth model with economy-wide increasing returns, in which a public input is essential for private production. Within such a framework, it is shown that a continuum of equilibria and global indeterminacy can arise for reasonable parameter values, simply due to the presence of endogenous public policy. This can potentially account for "leapfrogging" or retroceding growth experiences. It is demonstrated how fiscal policy can serve as a selection device among different convergent paths. Copyright Blackwell Publishing Ltd 2003
Sporting and cultural events: contested legacies

Whereas the language of legacy has dominated sport and cultural event narratives over the last two decades, in recent years there has been a greater recognition that the outcomes of these events do not happen automatically but instead need to be planned, resourced, and led by a range of partners and funders (Gratton and Preuss 2008; Misener and Mason 2010; Foley, McGillivray, and McPherson 2011). In academic and policy communities there is debate over the most useful strategies and tactics used to ensure that the beneficiaries of these events are considered in advance, during delivery and in the period beyond (Chalip 2006; HM Government 2013). On one level, sporting and cultural events have been credited with the potential to change perceptions of cities and nations and act as a catalyst for change. Yet, on another, there is significant contestation over the value of these events and their impact on the people and places affected by their delivery. Though the language of legacy is now ubiquitous when considering the justification for bidding and delivering large-scale sporting and cultural events, it is important to recognize its relative newness in historical terms. Sport events were only institutionalized in the late nineteenth century and there was little discussion at that time of the need for explicit, measurable legacies, captured in the frameworks and plans commonplace today. On the contrary, festivals and other celebrations rich in ritual and symbolism were common in the pre-industrial period, where events were planned around seasonal cycles, organized by and for communities and with minimal (if any) public investment or requirement for post hoc rationalization as to their value. However, when we fast forward to the early part of the twenty-first century, we encounter an events industry, or ecology, that positions organized, planned celebrations of sport and culture at the forefront of local, national and international policies and practices designed to deliver economic, social, political and environmental benefits. Liminality, libidinous behaviour and laissez faire attitudes are supplanted with an emphasis on image enhancement, economic regeneration, media activation and the achievement of social externalities. In effect, over the last three decades, we have witnessed a shift from:
HBV Core Particles Allow the Insertion and Surface Exposure of the Entire Potentially Protective Region of Puumala Hantavirus Nucleocapsid Protein

Abstract Core particles of the hepatitis B virus (HBV) potentiate the immune response against foreign epitopes presented on their surface. Potential insertion sites in the monomeric subunit of the HBV core protein were previously identified at the N- and C-terminus and in the immunodominant c/e1 region. In a C-terminally truncated core protein these sites were used to introduce the entire 120 amino acid (aa)-long potentially immunoprotective region of the hantavirus (serotype Puumala) nucleocapsid protein. The N- and C-terminal fusion products were unable to form core-like particles in detectable amounts. However, a suppressable stop codon located between the HBV core and the C-terminally fused hantavirus sequence restored the ability to form particles (‘mosaic particles’); in contrast to the C-terminal fusion product the mosaic construct allowed the formation of particles built up by the core protein itself and the HBV core-Puumala nucleocapsid- readthrough protein. The mosaic particles exposed the 120 aa region of the PUU nucleocapsid protein on their surface as demonstrated by ELISA and immuno electron microscopy applying different monoclonal antibodies. Insertion of the hantaviral sequence into the c/e1 region not only allowed the formation of chimeric particles, but again the surface accessibility of the sequence. HBV core antigenicity itself was, however, reduced in the particles carrying insertions in the c/e1 region, probably due to a masking effect of the 120 aa long insert.
Radiographic anatomy of pulpal chambers of primary molars.

The radiographic anatomy of the superior borders of pulpal chambers of primary molars was studied to clarify interpretation of superimposing cuspal images. First and second maxillary and mandibular molars were sectioned transaxially in the cervical region. The pulpal tissue was replaced by radiopaque resin before embedding the crowns in clear plastic blocks and obtaining buccolingual radiographs. The embedded crowns were then sectioned mesiodistally and radiographed buccolingually. The postsectional radiographic outlines of the pulpal chambers then were compared to presectional radiographs. An average radiographic image for each tooth type was constructed from a median of the aggregate tracings of the particular tooth. The radiographic appearance of each primary molar presented two to five overlapping pulpal horns, corresponding to their morphological anatomies. On dental radiographs, the lingual pulpal outline is sharper and more radiopaque than the buccal pulpal outline.
Comparison of phenobarbitone, phenytoin with sodium valproate: randomized, double-blind study.

OBJECTIVE To compare the efficacy and side effects of phenobarbitone (PB), phenytoin (PHT) and sodium valproate (SVP) in controlling generalized tonic-clonic convulsions (GTC). DESIGN Randomized, double blind clinical trial. SETTING Out-Patients in a tertiary care hospital. PATIENTS 151 children with GTC, aged 4-12 yrs, from Madras city were enrolled. At the end of 2 yrs, 127 children remained in the study. INTERVENTION Each child was given one active drug and 2 placebo tablets. Clinical, hematological and biochemical evaluations were done every month. Serum drug levels were assessed periodically. MAIN OUTCOME MEASURES Recurrence of convulsion and side effects. RESULTS The proportion of children with recurrence did not differ among the 3 groups. More than one side effect was observed in 16 (32%) children on PB, 20 (40%) children on PHT and 9 (19%) children on SVP and this difference was statistically significant (p < 0.05). Hyperactivity was the major side effect of PB, observed in 22% of children. CONCLUSION All 3 drugs were equally effective in controlling seizures. Side effects were minimal with SVP followed by PB. Though side effects were more frequent with PHT, most of them disappeared on adjusting drug dosage. Least expensive phenobarbitone may be preferred as the first drug of choice but, only for pre-school children. SVP is advised for school going children.