bluuebunny/crossref_metadata_2025 huggingface dataset:
Autocrine Fibroblast Growth Factor 2 Increases the Multipotentiality of Human Adipose-Derived Mesenchymal Stem Cells
Authors: Rider David A. , Dombrowski Christian , Sawyer Amber A. , Ng Grace H. B. , Leong David , Hutmacher Dietmar W. , Nurcombe Victor , Cool Simon M.
Published: March 2008

Multipotent mesenchymal stem cells (MSCs), first identified in the bone marrow, have subsequently been found in many other tissues, including fat, cartilage, muscle, and bone. Adipose tissue has been identified as an alternative to bone marrow as a source for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of bone marrow-derived mesenchymal stem cells (BMSCs) with that of adipose-derived mesenchymal stem cells (AMSCs) from 12 age- and sex-matched donors. Phenotypically, the cells are very similar, with only three surface markers, CD106, CD146, and HLA-ABC, differentially expressed in the BMSCs. Although colony-forming units-fibroblastic numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, like that of fibroblast growth factor 2 (FGF2), the Wnt pathway effectors FRAT1 and frizzled 1, and other self-renewal markers, was greater in AMSCs. Furthermore, AMSCs displayed enhanced osteogenic and adipogenic potential, whereas BMSCs formed chondrocytes more readily than AMSCs. However, by removing the effects of proliferation from the experiment, AMSCs no longer out-performed BMSCs in their ability to undergo osteogenic and adipogenic differentiation. Inhibition of the FGF2/fibroblast growth factor receptor 1 signaling pathway demonstrated that FGF2 is required for the proliferation of both AMSCs and BMSCs, yet blocking FGF2 signaling had no direct effect on osteogenic differentiation.

Disclosure of potential conflicts of interest is found at the end of this article.
Derivation and Cloning of a Novel Rhesus Embryonic Stem Cell Line Stably Expressing Tau-Green Fluorescent Protein
Authors: Wianny Florence , Bernat Agnieszka , Huissoud Cyril , Marcy Guillaume , Markossian Suzy , Cortay Véronique , Giroud Pascale , Leviel Vincent , Kennedy Henry , Savatier Pierre , Dehay Colette
Published: March 2008

Embryonic stem cells (ESC) have the ability of indefinite self-renewal and multilineage differentiation, and they carry great potential in cell-based therapies. The rhesus macaque is the most relevant preclinical model for assessing the benefit, safety, and efficacy of ESC-based transplantations in the treatment of neurodegenerative diseases. In the case of neural cell grafting, tracing both the neurons and their axonal projections in vivo is essential for studying the integration of the grafted cells in the host brain. Tau-Green fluorescent protein (tau-GFP) is a powerful viable lineage tracer, allowing visualization of cell bodies, dendrites, and axons in exquisite detail. Here, we report the first rhesus monkey ESC line that ubiquitously and stably expresses tau-GFP. First, we derived a new line of rhesus monkey ESC (LYON-ES1) that show marker expression and cell cycle characteristics typical of primate ESCs. LYON-ES1 cells are pluripotent, giving rise to derivatives of the three germ layers in vitro and in vivo through teratoma formation. They retain all their undifferentiated characteristics and a normal karyotype after prolonged culture. Using lentiviral infection, we then generated a monkey ESC line stably expressing tau-GFP that retains all the characteristics of the parental wild-type line and is clonogenic. We show that neural precursors derived from the tau-GFP ESC line are multipotent and that their fate can be precisely mapped in vivo after grafting in the adult rat brain.

Disclosure of potential conflicts of interest is found at the end of this article.
Conditional Stabilization ofβ-Catenin Expands the Pool of Lung Stem Cells
Authors: Reynolds Susan D. , Zemke Anna C. , Giangreco Adam , Brockway Brian L. , Teisanu Roxana M. , Drake Jeffrey A. , Mariani Thomas , Di Peter Y.P. , Taketo Mark M. , Stripp Barry R.
Published: March 2008

Maintenance of classic stem cell hierarchies is dependent upon stem cell self-renewal mediated in part by Wnt/β-catenin regulation of the cell cycle. This function is critical in rapidly renewing tissues due to the obligate role played by the tissue stem cell. However, the stem cell hierarchy responsible for maintenance of the conducting airway epithelium is distinct from classic stem cell hierarchies. The epithelium of conducting airways is maintained by transit-amplifying cells in the steady state; rare bronchiolar stem cells are activated to participate in epithelial repair only following depletion of transit-amplifying cells. Here, we investigate how signaling through β-catenin affects establishment and maintenance of the stem cell hierarchy within the slowly renewing epithelium of the lung. Conditional potentiation of β-catenin signaling in the embryonic lung results in amplification of airway stem cells through attenuated differentiation rather than augmented proliferation. Our data demonstrate that the differentiation-modulating activities of stabilized β-catenin account for expansion of tissue stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.
An Efficient Two-Stage Sampling Method for Uncertainty Quantification in History Matching Geological Models
Authors: Ma Xianlin , Al-Harbi Mishal , Datta-Gupta Akhil , Efendiev Yalchin
Published: March 2008

The paper presents a novel method for rapid quantification of uncertainty in history matching reservoir models using a two-stage Markov Chain Monte Carlo (MCMC) method. Our approach is based on a combination of fast linearized approximation to the dynamic data and the MCMC algorithm. In the first stage, we use streamline-derived sensitivities to obtain an analytical approximation in a small neighborhood of the previously computed dynamic data. The sensitivities can be conveniently obtained using either a finite-difference or streamline simulator. The approximation of the dynamic data is then used to modify the instrumental proposal distribution during MCMC. In the second stage, those proposals that pass the first stage are assessed by running full flow simulations to assure rigorousness in sampling. The uncertainty analysis is carried out by analyzing multiple models sampled from the posterior distribution in the Bayesian formulation for history matching. We demonstrate that the two-stage approach increases the acceptance rate, and significantly reduces the computational cost compared to conventional MCMC sampling without sacrificing accuracy. Finally, both 2D synthetic and 3D field examples demonstrate the power and utility of the two-stage MCMC method for history matching and uncertainty analysis.
Upscaling Discrete Fracture Characterizations to Dual-Porosity, Dual-Permeability Models for Efficient Simulation of Flow With Strong Gravitational Effects
Authors: Gong B. , Karimi-Fard M. , Durlofsky L. J.
Published: March 2008

The geological complexity of fractured reservoirs requires the use of simplified models for flow simulation. This is often addressed in practice by using flow modeling procedures based on the dual-porosity, dual-permeability concept. However, in most existing approaches, there is not a systematic and quantitative link between the underlying geological model [in this case, a discrete fracture model (DFM)] and the parameters appearing in the flow model.

In this work, a systematic upscaling procedure is presented to construct a dual-porosity, dual-permeability model from detailed discrete fracture characterizations. The technique, referred to as a multiple subregion (MSR) model, represents an extension of an earlier method that did not account for gravitational effects. The subregions (or subgrid) are constructed for each coarse block using the iso-pressure curves obtained from local pressure solutions of a discrete fracture model over the block. The subregions thus account for the fracture distribution and can represent accurately the matrix-matrix and matrix-fracture transfer. The matrix subregions are connected to matrices in vertically adjacent blocks (as in a dual-permeability model) to capture phase segregation caused by gravity. Two-block problems are solved to provide fracture-fracture flow effects. All connections in the coarse-scale model are characterized in terms of upscaled transmissibilities, and the resulting coarse model can be used with any connectivity-based reservoir simulator.

The method is applied to simulate 2D and 3D fracture models, with viscous, gravitational, and capillary pressure effects, and is shown to provide results in close agreement with the underlying DFM. Speedups of approximately a factor of 120 are observed for a complex 3D example.
Applicability of the Forchheimer Equation for Non-Darcy Flow in Porous Media
Authors: Huang H. , Ayoub J.
Published: March 2008

The subject of non-Darcy flow in hydraulically fractured wells has generated intense debates recently. One aspect of the discussion concerns the inertia resistance factor, or the so-called beta factor, β, in the Forchheimer equation, and whether the beta factor β of a proppant pack should be constant over the range of flow rates of practical interests. The problem was highlighted in a recent discussion by van Batenburg and Milton-Tayler (2005) and the reply by Barree and Conway (2005) regarding paper SPE 89325 (Barree and Conway 2004) in the August 2005 JPT.

This discussion in essence revolves around the applicability of the Forchheimer equation and whether the Forchheimer equation is adequate to describe the experimental results of high rate flow in proppant packs. In order to properly assess the arguments in this debate, and to get a better understanding of the state-of-the-art on non-Darcy flow in porous media in general, literature concerning the theoretical basis of the Forchheimer equation and experimental work on the identification of flow regimes is reviewed. These areas of work provide insights into the applicability of the Forchheimer equation to conventional oilfield flow tests for proppant packs. Models for flow beyond the Forchheimer regime are also suggested.
Impact of Acid Additives on the Rheological Properties of a Viscoelastic Surfactant and Their Influence on Field Application
Authors: Nasr-El-Din Hisham A. , Al-Ghamdi AbdulWahab H. , Al-Qahtani Abdulqader A. , Samuel Mathew M.
Published: March 2008

This paper examines a new class of viscoelastic surfactants (amphoteric) that are used to enhance sweep efficiency during matrix acid treatments. It appears that surfactant molecules align themselves and form rod-shaped micelles once the acid is spent. These micelles might cause the viscosity to significantly increase, and induce viscoelastic properties to the spent acid. The enhancement in these properties depends on the micelle shape and magnitude of entanglement.

The effects of acid additives and contaminants [mainly iron (III)] on the rheological properties of these systems were examined over a wide range of parameters. Viscosity measurements were conducted using specially designed viscometers to handle very corrosive fluids. Measurements were made between 25 and 100°C, and at 300 psi at various shear rates from 58 to 1,740 s−1. Acid additives included corrosion inhibitors, inhibitor aids, an iron control agent, a hydrogen sulfide scavenger, an anti-sludge agent, and a nonionic surfactant. Effects of mutual solvents and methanol on the apparent viscosity were also investigated.

It is observed that temperature, pH, shear conditions, and acid additives have a profound influence on the apparent viscosity of the surfactant-acid system. The viscosity and related properties are very different from what were observed with both natural and synthetic polymers. The differences in these properties were characterized and correlated with the type and nature of the additives used. Optimum conditions for better fluid performance in the field were derived.
Review of the Molecular Structure and Aggregation of Asphaltenes and Petroleomics
Authors: Mullins Oliver C.
Published: March 2008

Tremendous strides have been made recently in asphaltene science. Many advanced analytical techniques have been applied recently to asphaltenes, elucidating many asphaltene properties. The inability of certain techniques to provide correct asphaltene parameters has also been clarified. Longstanding controversies have been resolved. For example, molecular structural issues of asphaltenes have been resolved; in particular, asphaltene molecular weight is now known. The primary aggregation threshold has recently been established by a variety of techniques. Characterization of asphaltene interfacial activity has advanced considerably. The hierarchy of asphaltene aggregation has emerged into a fairly comprehensive picture, essentially in accord with the Yen model with the additional inclusion of certain constraints. Crude oil and asphaltene science is now poised to develop proper structure-function relations that are the defining objective of the new field: petroleomics. The purpose of this paper is to review these developments in order to present a more clear and accessible picture of asphaltenes, especially considering that the asphaltene literature is a bit opaque.
Favorable Attributes of Alkaline-Surfactant-Polymer Flooding
Authors: Liu Shunhua , Zhang Danhua Leslie , Yan Wei , Puerto Maura , Hirasaki George J. , Miller Clarence A.
Published: March 2008

A laboratory study of the alkaline-surfactant-polymer (ASP) process was conducted. It was found from phase-behavior studies that for a given synthetic surfactant and crude oil containing naph-thenic acids, optimal salinity depends only on the ratio of the moles of soap formed from the acids to the moles of synthetic surfactant present. Adsorption of anionic surfactants on carbonate surfaces is reduced substantially by sodium carbonate, but not by sodium hydroxide. The magnitude of the reduction with sodium carbonate decreases with increasing salinity.

Particular attention was given to a surfactant blend of a pro-poxylated sulfate having a slightly branched C16–17 hydrocarbon chain and an internal olefin sulfonate. In contrast to alkyl/aryl sulfonates previously considered for EOR, alkaline solutions of this blend containing neither alcohol nor oil were single-phase micellar solutions at all salinities up to approximately optimal salinity with representative oils. Phase behavior with a west Texas crude oil at ambient temperature in the absence of alcohol was unusual in that colloidal material, perhaps another microemulsion having a higher soap content, was dispersed in the lower-phase microemulsion. Low interfacial tensions existed with the excess oil phase only when this material was present in sufficient amount in the spinning-drop device. Some birefringence was observed near and above optimal conditions. While this phase behavior is somewhat different from the conventional Winsor phase sequence, overall solubilization of oil and brine for this system was high, leading to low interfacial tensions over a wide salinity range and to excellent oil recovery in both dolomite and silica sandpacks. The sandpack experiments were performed with surfactant concentrations as low as 0.2 wt% and at a salinity well below optimal for the injected surfactant. It was necessary that sufficient polymer be present to provide adequate mobility control, and that salinity be below the value at which phase separation occurred in the polymer/surfactant solution.

A 1D simulator was developed to model the process. By calculating transport of soap formed from the crude oil and injected surfactant separately, it showed that injection below optimal salinity was successful because a gradient in local soap-to-surfactant ratio developed during the process. This gradient increases robustness of the process in a manner similar to that of a salinity gradient in a conventional surfactant process. Predictions of the simulator were in excellent agreement with the sandpack results.
RhoA/Rho-Kinase Contribute to the Pathogenesis of Diabetic Renal Disease
Authors: Peng Fangfang , Wu Dongcheng , Gao Bo , Ingram Alistair J. , Zhang Baifang , Chorneyko Katherine , McKenzie Rick , Krepinsky Joan C.
Published: March 2008

OBJECTIVE—Accumulation of glomerular matrix proteins is central to the pathogenesis of diabetic nephropathy, with resident mesangial cells (MCs) known to upregulate matrix protein synthesis in response to high glucose. Because activation of the GTPase RhoA has been implicated in matrix upregulation, we studied its role in induction of the matrix protein fibronectin in diabetic MCs and in vivo in diabetic nephropathy.

RESEARCH DESIGN AND METHODS—Glucose (30 mmol/l)-induced RhoA/Rho-kinase, AP-1 activation, and fibronectin upregulation were assessed by immunoblotting, luciferase, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, real-time PCR, Northern blots, and immunofluorescence. Streptozotocin-induced diabetic rats were treated with the ρ-kinase inhibitor fasudil, which was compared with enalapril, and functional and pathologic parameters were assessed.

RESULTS—Glucose led to RhoA and downstream Rho-kinase activation. Mannitol was without effect. Activity of the transcription factor AP-1, increased in diabetic MCs and kidneys, is important in the profibrotic effects of glucose, and this was dependent on Rho-kinase signaling. Upregulation of fibronectin by glucose, shown to be mediated by activator protein-1 (AP-1), was prevented by Rho-kinase inhibition. RhoA siRNA and dominant-negative RhoA also markedly attenuated fibronectin upregulation by high glucose. Applicability of these findings were tested in vivo. Fasudil prevented glomerular fibronectin upregulation, glomerular sclerosis, and proteinuria in diabetic rats, with effectiveness similar to enalapril.

CONCLUSIONS—High glucose activates RhoA/Rho-kinase in MCs, leading to downstream AP-1 activation and fibronectin induction. Inhibition of this pathway in vivo prevents the pathologic changes of diabetic nephropathy, supporting a potential role for inhibitors of RhoA/Rho in the treatment of diabetic renal disease.
The Diabetic Phenotype in HNF4A Mutation Carriers Is Moderated By the Expression of HNF4A Isoforms From the P1 Promoter During Fetal Development
Authors: Harries Lorna W. , Locke Jonathan M. , Shields Beverley , Hanley Neil A. , Hanley Karen Piper , Steele Anna , Njølstad Pål R. , Ellard Sian , Hattersley Andrew T.
Published: March 2008

OBJECTIVE—Mutations in the alternatively spliced HNF4A gene cause maturity-onset diabetes of the young (MODY). We characterized the spatial and developmental expression patterns of HNF4A transcripts in human tissues and investigated their role as potential moderators of the MODY phenotype.

RESEARCH DESIGN AND METHODS—We measured the expression of HNF4A isoforms in human adult tissues and gestationally staged fetal pancreas by isoform-specific real-time PCR. The correlation between mutation position and age of diagnosis or age-related penetrance was assessed in a cohort of 190 patients with HNF4A mutations.

RESULTS—HNF4A was expressed exclusively from the P2 promoter in adult pancreas, but from 9 weeks until at least 26 weeks after conception, up to 23% of expression in fetal pancreas was of P1 origin. HNF4A4–6 transcripts were not detected in any tissue. In whole pancreas, HNF4A9 expression was greater than in islets isolated from the endocrine pancreas (relative level 22 vs. 7%). Patients with mutations in exons 9 and 10 (absent from HNF4A3, HNF4A6, and HNF4A9 isoforms) developed diabetes later than those with mutations in exons 2–8, where all isoforms were affected (40 vs. 24 years; P = 0.029). Exon 9/10 mutations were also associated with a reduced age-related penetrance (53 vs. 10% without diabetes at age 55 years; P < 0.00001).

CONCLUSIONS—We conclude that isoforms derived from the HNF4A P1 promoter are expressed in human fetal, but not adult, pancreas, and that their presence during pancreatic development may moderate the diabetic phenotype in individuals with mutations in the HNF4A gene.
Suppressors of Cytokine-Signaling Proteins Induce Insulin Resistance in the Retina and Promote Survival of Retinal Cells
Authors: Liu Xuebin , Mameza Marie G. , Lee Yun Sang , Eseonu Chikezie I. , Yu Cheng-Rong , Kang Derwent Jennifer J. , Egwuagu Charles E.
Published: March 2008

OBJECTIVE—Suppressors of cytokine signaling (SOCS) are implicated in the etiology of diabetes, obesity, and metabolic syndrome. Here, we show that some SOCS members are induced, while others are constitutively expressed, in retina and examine whether persistent elevation of SOCS levels in retina by chronic inflammation or cellular stress predisposes to developing insulin resistance in retina, a condition implicated in diabetic retinopathy.

RESEARCH DESIGN AND METHODS—SOCS-mediated insulin resistance and neuroprotection in retina were investigated in 1) an experimental uveitis model, 2) SOCS1 transgenic rats, 3) insulin-deficient diabetic rats, 4) retinal cells depleted of SOCS6 or overexpressing SOCS1/SOCS3, and 5) oxidative stress and light-induced retinal degeneration models.

RESULTS—We show that constitutive expression of SOCS6 protein in retinal neurons may improve glucose metabolism, while elevated SOCS1/SOCS3 expression during uveitis induces insulin resistance in neuroretina. SOCS-mediated insulin resistance, as indicated by its inhibition of basally active phosphoinositide 3-kinase/AKT signaling in retina, is validated in retina-specific SOCS1 transgenic rats and retinal cells overexpressing SOCS1/SOCS3. We further show that the SOCS3 level is elevated in retina by oxidative stress, metabolic stress of insulin-deficient diabetes, or light-induced retinal damage and protects ganglion cells from apoptosis, suggesting that upregulation of SOCS3 may be a common physiologic response of neuroretinal cells to cellular stress.

CONCLUSIONS—Our data suggest two-sided roles of SOCS proteins in retina. Whereas SOCS proteins may improve glucose metabolism, mitigate deleterious effects of inflammation, and promote neuroprotection, persistent SOCS3 expression caused by chronic inflammation or cellular stress can induce insulin resistance and inhibit neurotrophic factors, such as ciliary neurotrophic factor, leukemia inhibitory factor, and insulin, that are essential for retinal cell survival.
Pharmacokinetics of gallium maltolate after intragastric administration in neonatal foals
Authors: Martens Ronald J. , Mealey Katrina , Cohen Noah D. , Harrington Jessica R. , Chaffin M. Keith , Taylor Robert J. , Bernstein Lawrence R.
Published: March 2008

Objective—To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in healthy foals.

Animals—6 healthy neonatal foals.

Procedures—Each foal received GaM (20 mg/kg) by intragastric administration. Blood samples were obtained before (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hours after GaM administration for determination of serum gallium concentrations by use of inductively coupled plasma mass spectroscopy.

Results—Mean ± SD pharmacokinetic variables were as follows: peak serum gallium concentration, 1,079 ± 311 ng/mL; time to peak serum concentration, 4.3 ± 2.0 hours; area under the serum concentration versus time curve, 40,215 ± 8,420 ng/mL/h; mean residence time, 39.5 ± 17.2 hours; area under the moment curve, 1,636,554 ± 931,458 ng([h]2/mL); and terminal half-life, 26.6 ± 11.6 hours. The mean serum concentration of gallium at 12 hours was 756 ± 195 ng/mL.

Conclusions and Clinical Relevance—Gallium maltolate administered via nasogastric tube at a dose of 20 mg/kg to neonatal foals resulted in gallium serum concentrations considered sufficient to suppress growth or kill Rhodococcus equi in macrophages and other infected tissues.
Modulation of the tissue reninangiotensin-aldosterone system in dogs with chronic mild regurgitation through the mitral valve
Authors: Fujii Yoko , Orito Kensuke , Muto Makoto , Wakao Yoshito
Published: March 2008

Objective—To investigate whether the tissue and plasma renin-angiotensin-aldosterone system (RAAS) is activated in dogs with mild regurgitation through the mitral valve and determine the contribution of chymase and angiotensin-converting enzyme (ACE) to the activation of the RAAS and potential production of angiotensin II during the chronic stage of mild mitral valve regurgitation.

Animals—5 Beagles with experimentally induced mild mitral valve regurgitation and 6 clinically normal (control) Beagles.

Procedures—Tissue ACE and chymase-like activities and plasma RAAS were measured and the RAAS evaluated approximately 1,000 days after experimental induction of mitral valve regurgitation in the 5 dogs.

Results—Dogs with experimentally induced mitral valve regurgitation did not have clinical signs of the condition, although echocardiography revealed substantial eccentric hyper- trophy. On the basis of these findings, dogs with mitral valve regurgitation were classified as International Small Animal Cardiac Health Council class Ib. Plasma activity of renin and plasma concentrations of angiotensin I, angiotensin II, and aldosterone were not significantly different between dogs with mitral valve regurgitation and clinically normal dogs. Tissue ACE activity was significantly increased and chymase-like activity significantly decreased in dogs with mitral valve regurgitation, compared with values in clinically normal dogs.

Conclusions and Clinical Relevance—The tissue RAAS was modulated without changes in the plasma RAAS in dogs with mild mitral valve regurgitation during the chronic stage of the condition. An ACE-dependent pathway may be a major route for production of angiotensin II during this stage of the condition.
Digestive enzyme concentrations and activities in healthy pancreatic tissue of horses
Authors: Lorenzo-Figueras Mireia , Morisset Sophie M. , Morisset Jean , Lainé Jean , Merritt Alfred M.
Published: March 2008

Objective—To measure concentrations and activities of major digestive enzymes in healthy equine pancreatic tissue.

Animals—7 adult horses with normal pancreatic tissues.

Procedures—Small pieces of pancreatic tissue were collected immediately after euthanasia, immersed in liquid nitrogen, and maintained at −80°C until analyzed. Concentrations and activities of amylase, lipase, chymotrypsin, trypsin, and elastase were determined by use of a microtiter technique. Relative pancreatic protein concentrations were determined by use of bovine serum albumin as the standard. Pancreatic DNA was extracted and con-centrations determined by use of the diphenylamine method with calf thymus DNA as the standard.

Results—The pancreatic cellular concentration of each enzyme, expressed as units per milligram of DNA, was consistent among horses. Cellular concentration of lipase (1,090.8 ± 285.3 U/mg of DNA) was highest, followed by amylase (59.5 ± 9.8 U/mg of DNA). Elastase, trypsin, and chymotrypsin were detected in small concentrations (1.9 ± 0.6, 3.5 ± 1.5, and 9.6 ± 2.9 U/mg of DNA, respectively). Similar results were obtained for specific activities of the enzymes.

Conclusions and Clinical Relevance—Results were unexpected because, under natural conditions, the predominant energy source for horses is carbohydrate. These results may indicate, in part, the reason horses seem to tolerate large amounts of fat added to their diet.
Assessment of antiepileptic drugs as substrates for canine P-glycoprotein
Authors: West Chadwick L. , Mealey Katrina L.
Published: March 2008

Objective—To determine whether antiepileptic drugs (AEDs) are substrates for canine P-glycoprotein (P-gp).

Sample Population—OS2.4/Doxo cells (canine osteosarcoma cells induced via exposure to doxorubicin to highly express P-gp).

Procedures—Competitive inhibition of rhodamine 123 efflux from OS2.4/Doxo cells was used to determine whether AEDs were substrates for canine P-gp. Flow cytometry was used to quantify mean fluorescence intensity of cells treated with rhodamine alone and in combination with each experimental drug.

Results—Known P-gp substrate drugs ivermectin and cyclosporin A altered rhodamine efflux by 90% and 95%, respectively. Experimental drugs altered rhodamine efflux weakly (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or not at all (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide).

Conclusions and Clinical Relevance—At clinically relevant doses, it appeared that AEDs were weak substrates (diazepam, gabapentin, lamotrigine, levetiracetam, and phenobarbital) or were not substrates (carbamazepine, felbamate, phenytoin, topirimate, and zonisamide) for canine P-gp. Therefore, it seems unlikely that efficacy of these AEDs is affected by P-gp expression at the blood-brain barrier in dogs.
Comparison of ophthalmic measurements obtained via high-frequency ultrasound imaging in four species of snakes
Authors: Hollingsworth Steven R. , Holmberg Bradford J. , Strunk Anneliese , Oakley Alicia D. , Sickafoose Leann M. , Kass Philip H.
Published: March 2008

Objective—To measure the dimensions of the eyes of living snakes by use of high-frequency ultrasound imaging and correlate those measurements with age, length, and weight.

Animals—14 clinically normal snakes.

Procedures—Species, age, length, weight, and horizontal spectacle diameter were recorded, and each snake underwent physical and ophthalmic examinations; ultrasonographic examination of both eyes was performed by use of a commercially available ultrasound unit and a 50-MHz transducer. Ultrasonographic measurements included spectacle thickness, subspectacular space depth, corneal thickness, anterior chamber depth, lens thickness, vitreous cavity depth, and globe length. All measurements were made along the visual axis.

Results—2 corn snakes, 5 California king snakes, 1 gopher snake, and 6 ball pythons were examined. There were no significant differences within or between the species with regard to mean spectacle thickness, corneal thickness, or subspectacular space depth. However, mean horizontal spectacle diameter, anterior chamber depth, and axial globe length differed among the 4 species; for each measurement, ball pythons had significantly larger values than California king snakes.

Conclusions and Clinical Relevance—Spectacle thickness, subspectacular space depth, and corneal thickness were similar among the species of snake examined and did not vary significantly with age, length, or weight. Measurements of these dimensions can potentially serve as baseline values to evaluate snakes of these species with a retained spectacle, subspectacular abscess, or subspectacular fluid accumulation. Anterior chamber depth and axial length appeared variable among species, but axial length did not vary with age, length, or weight in the species studied.
Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses
Authors: Colitz Carmen M. H. , Latimer Federico G. , Cheng Hao , Chan Ken K. , Reed Stephen M. , Pennick Genneth J.
Published: March 2008

Objective—To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses.

Animals—6 clinically normal adult horses.

Procedures—All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed.

Results—Mean ± SD volume of distribution at steady state was 1,604.9 ± 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 ± 19%; the highest plasma concentration of 6.1 ± 1.4 μg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 μg/mL, and mean trough plasma concentration was 1.32 μg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 ± 1.594 μg/mL, 2.508 ± 1.616 μg/mL, 3.073 ± 2.093 μg/mL, 4.422 ± 0.8095 μg/mL, and 3.376 ± 1.297 μg/mL, respectively.

Conclusions and Clinical Relevance—Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.
Effects of foodborne Fusarium mycotoxins with and without a polymeric glucomannan mycotoxin adsorbent on food intake and nutrient digestibility, body weight, and physical and clinicopathologic variables of mature dogs
Authors: Leung Maxwell C. K. , Smith Trevor K. , Karrow Niel A. , Boermans Herman J.
Published: March 2008

Objective—To investigate the effects of feeding cereal-based diets that are naturally contaminated with Fusarium mycotoxins to dogs and assess the efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) in prevention of Fusarium mycotoxicosis.

Animals—12 mature female Beagles.

Procedures—Dogs received each of 3 cereal-based diets for 14 days. One diet was uncontaminated (control diet), and the other 2 contained contaminated grains; one of the contaminated diets also contained 0.2% GMA. Contaminants included deoxynivalenol, 15-acetyl deoxynivalenol, zearalenone, and fusaric acid. Food intake and nutrient digestibility, body weight, blood pressure, heart rate, and clinicopathologic variables of the dogs were assessed at intervals during the feeding periods.

Results—Food intake and body weight of dogs fed the contaminated diet without GMA were significantly decreased, compared with effects of the control diet. Reductions in blood pressure; heart rate; serum concentrations of total protein, globulin, and fibrinogen; and serum activities of alkaline phosphatase and amylase as well as increases in blood monocyte count and mean corpuscular volume were detected. Consumption of GMA did not ameliorate the effects of the Fusarium mycotoxins. For the GMA-contaminated diet, digestibility of carbohydrate, protein, and lipid was significantly higher than that associated with the control diet, possibly because of physiologic adaptation of the recipient dogs to reduced food intake.

Conclusions and Clinical Relevance—Results indicated that consumption of grains naturally contaminated with Fusarium mycotoxins can adversely affect dogs' feeding behaviors and metabolism. As a food additive, GMA was not effective in prevention of Fusarium mycotoxicosis in dogs.
Test-Retest Reliability and Minimal Detectable Change on Balance and Ambulation Tests, the 36-Item Short-Form Health Survey, and the Unified Parkinson Disease Rating Scale in People With Parkinsonism
Authors: Steffen Teresa , Seney Megan
Published: March 2008

Background and Purpose

Distinguishing between a clinically significant change and change due to measurement error can be difficult. The purpose of this study was to determine test-retest reliability and minimal detectable change for the Berg Balance Scale (BBS), forward and backward functional reach, the Romberg Test and the Sharpened Romberg Test (SRT) with eyes open and closed, the Activities-specific Balance Confidence (ABC) Scale, the Six-Minute Walk Test (6MWT), comfortable and fast gait speed, the Timed “Up & Go” Test (TUG), the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Unified Parkinson Disease Rating Scale (UPDRS) in people with parkinsonism.

Subjects

Thirty-seven community-dwelling adults with parkinsonism (mean age=71 years) participated. The Hoehn and Yahr Scale median score of 2 was on the lower end of the scale; however, the scores ranged from 1 to 4.

Methods

Subjects were tested twice by the same raters, with 1 week between tests. Test-retest reliability was calculated using intraclass correlation coefficients (ICCs). Minimal detectable change was calculated using a 95% confidence interval (MDC95).

Results

The ICCs for test-retest reliability were above .90 for the BBS, ABC Scale, SRT with eyes closed, 6MWT, and comfortable and fast gait speeds. The MDC95 values for those functional tests were: BBS=5/56, ABC Scale=13%, SRT with eyes closed=19 seconds, 6MWT=82 m, comfortable gait speed=0.18 m/s, and fast gait speed=0.25 m/s. The ICCs for test-retest reliability of SF-36 scores were above .80, with the exception of the social functioning subscale. The MDC95 values for the SF-36 ranged between 19% and 45%. The MDC95 values for the UPDRS Activities of Daily Living section, Motor Examination section, and total scores were 4/52, 11/108, and 13/176, respectively.

Discussion and Conclusion

Minimal detectable change values are useful to therapists in rehabilitation and wellness programs in determining whether change during or after intervention is clinically significant. High test-retest reliability of scores for the BBS, ABC Scale, SRT with eyes closed, 6MWT, and gait speed make them trustworthy functional assessments in people with parkinsonism. The SF-36 and UPDRS provide quality-of-life and disease severity rating values in the ongoing assessment of people with parkinsonism.
Towards Magnetic Molecule and Reagent Separation in Organic Synthesis: Development and Use of Covalently Functionalized Nanomagnets
Authors: Halim Samuel C. , Stark Wendelin J.
Published: March 2008

Preparative chemistry combines theoretical complexity and arduous practical work in the laboratory. As a result, chemists often spend long hours waiting for products to react, dry, separate, and crystallize or to be analyzed. Partial relief from waiting comes with today's broad access
to efficient and elegant synthetic methods. The present contribution addresses the time-consuming work between the actual chemical reaction steps where labor-intensive work is done manually. Even the most skillful chemists admit that reactions typically run on their own while personal time
is largely spent on the workup and, most important, on their planning. This article demonstrates how covalently functionalized cobalt nanomagnets can offer an unconventional way to significantly speed up separation of reagents or products in synthesis. Combining concepts from Merrifield chemistry
and making use of novel materials preparation methods, reagents or synthetic intermediates can now be covalently attached to nanomagnets. With a size range of 10–50 nm, the tiny metal particles have sufficient specific surface area to attach molecules at a capacity close to presently
used Wang resins or Merrifield chemistry. A synthesis can now be run in the presence of the magnetic helping agents and, if necessary, the tagged compounds can be removed from the reaction mixture within seconds. While magnetic molecule separation is still in its infancy, the present review
offers insight into the materials origins and first applications.
A Simple Straightforward Synthesis of Phenylphosphane and the Photoinitiator Bis(mesitoyl)phenylphosphane Oxide (IRGACURE 819)
Authors: Grützmacher Hansjörg , Murer Peter , Wolf Jean-Pierre , Boulmaaz Souad , Sommerlade Reinhard H. , Schönberg Hartmut , Ott Timo , Stein Daniel , Geier Jens , Ulrich Thomas
Published: March 2008

A straightforward high-yield synthesis for the photoinitiator bis(2,4,6-trimethylbenzoyl)phenylphosphane oxide (16, IRGACURE 819) involves: i) the reaction of phenyldichlorophosphane, PhPCl2, with sodium to give [Na2(P2Ph2)(tmeda)]6
(5); ii) protonation of 5 with tert-butanol to give 1,2-diphenyldiphosphane, PhHP-PHPh (12); iii) reduction of 12 by sodium to yield [Na(PHPh)]x (13); iv) protonation of 13 with tert-butanol to give phenylphosphane PhPH2
(14) in excellent yields; v) reaction of 14 with 2,4,6-trimethylbenzoylchloride (MesCOCl) in presence of the NaOt-Bu formed in steps ii and iv to give bis(2,4,6-trimethylbenzoyl)phenylphosphane 7; vi) oxygenation of 7 with 30% aqueous hydrogen peroxide to
give the final product 16. This reaction can be performed in toluene with about 4 vol-% of tmeda as an activator in a one-pot synthesis without changing the solvent. The structures determined by X-ray diffraction of the unique hexameric aggregate 5 and 16 are reported.
RheManTec 2007 – Joint Swiss – South African Research Symposium down the Manganese Triad
Authors: Alberto Roger , Roodt Andreas
Published: March 2008

RheManTec, the First Symposium on the Chemistry and Application of the Elements down the Manganese Triad was held near Bloemfontein in South Africa from November 19–24, 2007. The main objective was an open presentation of actual research achievements and interests from the field
of metal-containing anti-cancer drugs and catalysis in order to elucidate future joint research opportunities in public health and biomedicine. The symposium emerged from the joint efforts of the Swiss National Science Foundation and the National Research Foundation of South Africa to strengthen
bilateral co-operation.
Automated Synthesis of Oligosaccharides Provides Access to Chemical Tools and Vaccine Candidates
Authors: Kröck Lenz , Seeberger Peter H.
Published: March 2008

Defined, pure oligosaccharides are important tools for biologists to study the structure and function of carbohydrates in biological systems and to create novel diagnostic and therapeutic approaches. Access to reasonable quantities of sufficiently pure oligosaccharides by isolation
is difficult and time consuming. Synthetic chemists are therefore called upon to develop straightforward and reliable methods to produce carbohydrates. These molecules are key to the creation of molecular tools and vaccine candidate molecules. A brief overview of the state-of-the-art of automated
synthesis is followed by some illustrative examples to highlight applications.
Public Schools Versus Private Schools: Causal Inference With Partial Compliance
Authors: Jin Hui , Rubin Donald B.
Published: March 2008

An approach to handle partial compliance behavior using principal stratification is presented and applied to a subset of the longitudinal data from the New York City School Choice Scholarship Program, a randomized experiment designed to assess the effects of private schools versus public schools on academic achievement. The initial analysis suggests an interesting relationship between compliance with the offer and academic achievement, including a possible “beneficial rejected offer” effect and a possible “adjustment hardship” effect. These results seem to favor public schools in the sense they suggest that the collection of students who would attend private school when offered the scholarship but attend public school without the offer had a lower average posttest score if they attended private school than if they attended public school. This case study illustrates the strengths of principal stratification: the explicit examination of specific assumptions and directly interpretable results with possible policy implications.
Combining Heterogeneous Correlation Matrices: Simulation Analysis of Fixed-Effects Methods
Authors: Hafdahl Adam R.
Published: March 2008

Monte Carlo studies of several fixed-effects methods for combining and comparing correlation matrices have shown that two refinements improve estimation and inference substantially. With rare exception, however, these simulations have involved homogeneous data analyzed using conditional meta-analytic procedures. The present study builds on previous evidence about these methods’ relative performance by examining their behavior under heterogeneity, which is more realistic in practice. Results based on both conditional and unconditional estimands indicate that of the two refinements, using estimated correlations in conditional (co)variances improves point and interval estimates of mean correlations more than analyzing Fisher Z correlations, despite the latter’s superiority for testing homogeneity. Recommended choices among methods are offered.
Synthesis of a 4‐Selenothymidine Phosphoramidite and Incorporation into Oligonucleotides
Authors: Sheng Jia , Huang Zhen
Published: March 2008

The detailed synthetic protocol for a 4‐selenothymidine phosphoramidite and its use to prepare modified oligonucleotides is described here. The Se‐phosphoramidite synthesis was achieved by developing a useful protection and deprotection system for the selenium functionality. The coupling reaction of the Se‐phosphoramidite during solid‐phase oligonucleotide synthesis is quantitative, and the oligonucleotides containing the Se‐modification are stable. Based on crystal structure analysis, the selenium‐modified oligonucleotides retain base‐pairing like their native counterparts, and the derivatized DNA structure is virtually identical to the native structure. This achievement will present a novel opportunity for structural studies of nucleic acids and their protein complexes, because selenium can resolve the phase problem in macromolecular X‐ray crystallography. In addition, this atom‐specific replacement of oxygen with selenium will provide a useful tool for investigating biochemical and biophysical properties of nucleic acids and their protein complexes. Curr. Protoc. Nucleic Acid Chem. 32:1.19.1‐1.19.13. © 2008 by John Wiley & Sons, Inc.
Photoactivation and Imaging of Photoactivatable Fluorescent Proteins
Authors: Patterson George H.
Published: March 2008

A major advance in the microscopic study of cells and tissues is the introduction of photoactivatable fluorescent proteins, which can specifically mark proteins of interest within a living cell. Fluorescent proteins are now available that allow a pool of molecules to be “turned on” by photoactivation. This unit discusses technical aspects for the general use of photoactivatable fluorescent proteins and introduces some specific applications in the concluding remarks. Curr. Protoc. Cell Biol. 38:21.6.1‐21.6.10. © 2008 by John Wiley & Sons, Inc.
Using TESS to Predict Transcription Factor Binding Sites in DNA Sequence
Authors: Schug Jonathan
Published: March 2008

This unit describes how to use the Transcription Element Search System (TESS). This Web site predicts transcription factor binding sites (TFBS) in DNA sequence using two different kinds of models of sites, strings and positional weight matrices. The binding of transcription factors to DNA is a major part of the control of gene expression. Transcription factors exhibit sequence‐specific binding; they form stronger bonds to some DNA sequences than to others. Identification of a good binding site in the promoter for a gene suggests the possibility that the corresponding factor may play a role in the regulation of that gene. However, the sequences transcription factors recognize are typically short and allow for some amount of mismatch. Because of this, binding sites for a factor can typically be found at random every few hundred to a thousand base pairs. TESS has features to help sort through and evaluate the significance of predicted sites. Curr. Protoc. Bioinform. 21:2.6.1‐2.6.15. © 2008 by John Wiley & Sons, Inc.
Analysis of Gene‐Expression Data Using J‐Express
Authors: Stavrum Anne Kristin , Petersen Kjell , Jonassen Inge , Dysvik Bjarte
Published: March 2008

The J‐Express package has been designed to facilitate the analysis of microarray data with an emphasis on efficiency, usability, and comprehensibility. The J‐Express system provides a powerful and integrated platform for the analysis of microarray gene expression data. It is platform‐independent in that it requires only the availability of a Java virtual machine on the system. The system includes a range of analysis tools and a project management system supporting the organization and documentation of an analysis project. This unit describes the J‐Express tool, emphasizing central concepts and principles, and gives examples of how it can be used to explore gene expression data sets. Curr. Protoc. Bioinform. 21:7.3.1‐7.3.25. © 2008 by John Wiley & Sons, Inc.