bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Modification of Bone Quality by PTH, Pamidronate, or Raloxifene
Authors: Brennan Tara C , Rizzoli René , Ammann Patrick 
Published: December 2008

AbstractBone strength, a determinant of resistance to fracture, depends on BMD, geometry, microarchitecture, bone turnover rates, and properties of the bone at the material level. Despite comparable antifracture efficacy, anti-catabolics and bone anabolic agents are likely to modify the various determinants of bone strength in very different ways. Eight weeks after ovariectomy (OVX), 8-mo-old osteoporotic rats received pamidronate (APD; 0.6 mg/kg, 5 days/mo, SC), raloxifene (3 mg/kg, 5/7 days, tube feeding), PTH(1–34) (10 μg/kg, 5/7 days, SC), or vehicle for 16 wk, and we measured vertebral BMD, maximal load, stiffness and energy, microarchitecture, and material properties by nanoindentation, which allows the calculation of the elastic modulus, tissue hardness, and working energy. Markers of bone turnover, plasma osteocalcin, and urinary deoxypyridinoline (Dpd) were also determined. PTH induced greater maximal load than APD or raloxifene, as well as greater absorbed energy, BMD, and increased bone turnover markers. PTH markedly increased trabecular bone volume and connectivity to values higher than sham. Animals treated with APD had BV/TV values significantly higher than OVX but lower than sham, whereas raloxifene had no effect. Tissue hardness was identical in PTH-treated and OVX untreated controls. In contrast, APD reversed the decline in strength to levels not significantly different to sham, reduced bone turnover, and increased hardness. Raloxifene markedly increased material level cortical hardness and elastic modulus. These results show the different mechanisms by which anti-catabolics and bone anabolics reduce fracture risk. PTH influences microarchitecture, whereas bisphosphonates alter material-level bone properties, with probable opposite effects on remodeling space. Raloxifene primarily improved the material stiffness at the cortical level.
PTH and PTH Antagonist Induce Different Conformational Changes in the PTHR1 Receptor
Authors: Thomas Beena E , Sharma Sandhya , Mierke Dale F , Rosenblatt Michael 
Published: December 2008

Abstract
Interaction of ligands with their specific receptors is accompanied by conformational shifts culminating in receptor activation and expression of hormonal activity. Using an engineered disulfide bond formation strategy, we characterized the relative conformational changes taking place within the PTH type 1 receptor (PTHR1) at the interface of transmembrane (TM)5 and TM6 on binding the PTH agonist, PTH(1–34), compared with the antagonist PTH(7-34). Cysteines were singly incorporated into a portion of the extracellular-facing region of TM5 (365–370), while simultaneously a second cysteine was introduced at position 420, 423, or 425 at the extracellular end of TM6, leading to a total of 18 double cysteine-containing PTHR1 mutants. All mutants, except P366C/V423C and P366C/M425C, were expressed in the cell membrane preparations. In the presence of agonist, H420C and M425C in TM6 formed disulfide bonds with all and with most, respectively, of the substituted cysteines incorporated in TM5. In contrast to the conformational shift induced (or stabilized) by agonist in activating the receptor, antagonist binding produced no detectable change from the basal (inactive) conformation of PTHR1. Our studies provide physicochemical evidence that the extracellular-facing ligand binding regions of receptor, TM5 and TM6, are dynamic and move relative to each other on ligand binding. The distinct differences in receptor conformation induced (or stabilized) by agonist PTH(1–34) compared with antagonist PTH(7-34) begin to provide insight into the early events in and mechanism of PTHR1 activation.
Mathematical Modeling of Spatio-Temporal Dynamics of a Single Bone Multicellular Unit
Authors: Ryser Marc D , Nigam Nilima , Komarova Svetlana V 
Published: December 2008

Abstract
During bone remodeling, bone-resorbing osteoclasts and bone-forming osteoblasts are organized in bone multicellular units (BMUs), which travel at a rate of 20–40 μm/d for 6–12 mo, maintaining a cylindrical structure. However, the interplay of local BMU geometry with biochemical regulation is poorly understood. We developed a mathematical model of BMU describing changes in time and space of the concentrations of proresorptive cytokine RANKL and its inhibitor osteoprotegerin (OPG), in osteoclast and osteoblast numbers, and in bone mass. We assumed that osteocytes surrounding a microfracture produce RANKL, which attracted osteoclasts. OPG and RANKL were produced by osteoblasts and diffused through bone, RANKL was eliminated by binding to OPG and RANK. Osteoblasts were coupled to osteoclasts through paracrine factors. The evolution of the BMU arising from this model was studied using numerical simulations. Our model recapitulated the spatio-temporal dynamics observed in vivo in a cross-section of bone. In response to a RANKL field, osteoclasts moved as a well-confined cutting cone. The coupling of osteoclasts to osteoblasts allowed for sufficient recruitment of osteoblasts to the resorbed surfaces. The RANKL field was the highest at the microfracture in front of the BMU, whereas the OPG field peaked at the back of the BMU, resulting in the formation of a RANKL/OPG gradient, which strongly affected the rate of BMU progression and its size. Thus, the spatial organization of a BMU provides important constraints on the roles of RANKL and OPG as well as possibly other regulators in determining the outcome of remodeling in the BMU.
miR-196a Regulates Proliferation and Osteogenic Differentiation in Mesenchymal Stem Cells Derived From Human Adipose Tissue
Authors: Kim Yeon Jeong , Bae Sang Woo , Yu Sung Sook , Bae Yong Chan , Jung Jin Sup 
Published: December 2008

Abstract
The elucidation of the molecular mechanisms that govern the differentiation and proliferation of human adipose tissue-derived mesenchymal stem cells (hASCs) could improve hASC-based cell therapy. In this study, we examined the roles of microRNA (miRNA)-196a on hASC proliferation and osteogenic differentiation. Lentiviral overexpression of miR-196a decreased hASC proliferation and enhanced osteogenic differentiation, without affecting adipogenic differentiation. Overexpression of miR-196a decreased the protein and mRNA levels of HOXC8, a predicted target of miR-196a. HOXC8 expression was decreased during osteogenic differentiation of hASCs, and this decrease in HOXC8 expression was concomitant with an increase in the level of miR-196a. In contrast, inhibition of miR-196a with 2′-O-methyl-antisense RNA increased the protein levels of HOXC8 in treated hASCs and was accompanied by increased proliferation and decreased osteogenic differentiation. The activity of a luciferase construct containing the miR-196a target site from the HOXC8 3′UTR was lower in LV-miR196a-infected hASCs than in LV-miLacZ-infected cells. RNA interference-mediated downregulation of HOXC8 in hASCs increased their proliferation and decreased their differentiation into osteogenic cells, without affecting their adipogenic differentiation. Our data indicate that miR-196a plays a role in hASC osteogenic differentiation and proliferation, which may be mediated through its predicted target, HOXC8. This study provides us with a better knowledge of the molecular mechanisms that govern hASC differentiation and proliferation.
μCT-Based Measurement of Cortical Bone Graft-to-Host Union
Authors: Reynolds David G , Shaikh Saad , Papuga Mark Owen , Lerner Amy L , O'Keefe Regis J , Schwarz Edward M , Awad Hani A 
Published: December 2008

Abstract
Evaluation of structural bone grafts risk of failure requires noninvasive quantitative predictors of functional strength. We hypothesized that a quantitative graft-to-host union biometric would correlate significantly with biomechanical properties as a surrogate for the risk of fracture. To test this, we developed a novel algorithm to compute the union between host callus and graft, which was termed the union ratio. We compared the union ratio of live autografts to devitalized allografts implanted into the mid-diaphysis of mouse femurs for 6 and 9 wk. Surprisingly, the autograft union ratio decreased from 0.228 ± 0.029 at 6 wk to 0.15 ± 0.011 at 9 wk (p &lt; 0.05) and did not correlate with the torsional properties of the autografts. The allograft union ratio was 0.105 ± 0.023 at 6 wk but increased to 0.224 ± 0.029 at 9 wk (p &lt; 0.05). As a single variable, the union ratio correlated significantly with ultimate torque (R2 = 0.58) and torsional rigidity (R2 = 0.51) of the allografts. Multivariable regression analyses of allografts that included the union ratio, the graft bone volume, the maximum and minimum polar moment of inertia, and their first-order interaction terms with the union ratio as independent variables resulted in significant correlations with the ultimate torque and torsional rigidity (adjusted R2 = 0.80 and 0.89, respectively). These results suggest that, unlike live autografts, the union between the devitalized allograft and host contributes significantly to the strength of grafted bone. The union ratio has important clinical implications as a novel biometric for noninvasive assessment of functional strength and failure risk.
Clinical Vignette: PTH(1–34) Replacement Therapy in a Child With Hypoparathyroidism Caused by a Sporadic Calcium Receptor Mutation
Authors: Theman Todd A , Collins Michael T , Dempster David W , Zhou Hua , Reynolds James C , Brahim Jaime S , Roschger Paul , Klaushofer Klaus , Winer Karen K 
Published: December 2008

AbstractAutosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1–34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imaging (qBEI). Her data were compared with one age-, sex-, and length of hypoparathyroidism-matched control not on PTH and two sex-matched ADH controls before and after 1 yr of PTH. The patient's growth was normal. Hypercalciuria and hypermagnesuria persisted despite normal or subnormal serum calcium and magnesium levels. Nephrocalcinosis, without evidence of impaired renal function, developed by 19 yr of age. Cancellous bone volume was dramatically elevated in the patient and in ADH controls after 1 yr of PTH. BMD distribution (BMDD) by qBEI of the patient and ADH controls was strikingly shifted toward lower mineralization compared with the non-ADH control. Moreover, the ADH controls exhibited a further reduction in mineralization after 1 yr of PTH. These findings imply a role for CaR in bone matrix mineralization. There were no fractures or osteosarcoma. In conclusion, long-term PTH replacement in a child with ADH was not unsafe, increased bone mass without negatively impacting mineralization, and improved serum mineral control but did not prevent nephrocalcinosis. Additionally, this may be the first evidence of a role for CaR in human bone.
Plasma Osteocalcin Is Inversely Related to Fat Mass and Plasma Glucose in Elderly Swedish Men
Authors: Kindblom Jenny M , Ohlsson Claes , Ljunggren Östen , Karlsson Magnus K , Tivesten Åsa , Smith Ulf , Mellström Dan 
Published: December 2008

Abstract
The osteoblast-derived protein osteocalcin has recently been shown to affect adiposity and glucose homeostasis in mice, suggesting that the skeleton influences energy metabolism through an endocrine mechanism. The aim of this study was to investigate the relationship between plasma osteocalcin and parameters reflecting fat mass and glucose homeostasis in humans. Fasting levels of plasma osteocalcin, plasma glucose, serum insulin, and lipids were analyzed in elderly men (75.3 ± 3.2 yr of age) in the Gothenburg part (all subjects, n = 1010; nondiabetic, n = 857; diabetic, n = 153) of the MrOS Sweden study. Fat mass and lean mass were analyzed using DXA. Diabetic subjects had lower plasma osteocalcin (−21.7%, p &lt; 0.001) than nondiabetic subjects. For both all subjects and nondiabetic subjects, plasma osteocalcin was clearly inversely related to body mass index (BMI), fat mass, and plasma glucose (p &lt; 0.001), whereas it was not associated with height or lean mass. Plasma osteocalcin explained a substantial part (6.3%) of the variance in plasma glucose, whereas it associated moderately with serum insulin. Multiple linear regression models adjusting for serum insulin and fat mass showed that plasma osteocalcin was an independent negative predictor of plasma glucose (p &lt; 0.001). We herein, for the first time in humans, show that plasma osteocalcin is inversely related to fat mass and plasma glucose. Although one should be cautious with mechanistic interpretations of cross-sectional association studies, our human data support recently published experimental studies, showing endocrine functions of osteoblast-derived osteocalcin on glucose and fat homeostasis.
A Proposed Basis for Characterizing and Comparing the Permeation Resistance of Chemical Protective Clothing Materials
Authors: Spence MW 
Published: December 2008

A common problem among users of chemical protective clothing is the lack of a practical, consistent basis for comparing and characterizing the permeation barrier effectiveness of different protective clothing materials. This becomes a particular problem for generic materials (for example, neoprene) for which differences in raw materials, additives, and manufacturing techniques can result in differences in permeation resistance for the same material made by different manufacturers.
An approach to resolving this problem is described which uses permeation testing with a solubility-parameter-based set of test chemicals as a basis for comparing clothing materials. A proposed test battery is presented, and the rationale behind it, as well as its potential usefulness, is discussed.
Experiences from Developing a Data Base on the Protective Effects Against Chemicals of Gloves Made from Rubber and Plastic Materials
Authors: Mellström G 
Published: December 2008

A data base has been developed containing test data on protective effects of safety gloves against chemicals. Permeation data and clinical data as well as experimental data are collected and, after dermatological assessment, are put into different files in the data base. The main purpose of this data base is to give up-to-date and relevant information to those who have to choose and recommend suitable gloves to workers handling or working with hazardous chemicals. The information from the data base is presented to the users in the form of printed documents which can be updated regularly.
Today test results are not always comparable because so many different investigation methods are used. To make it possible to compare test results, still more work must be done to establish internationally accepted standards or reference methods (in vitro and in vivo) and internationally accepted rules for presenting test data. This would make it easier to evaluate the protective effect against chemicals of protective glove materials.
Efficiency of Protective Clothing for Pesticide Spraying
Authors: Lloyd GA 
Published: December 2008

Measurements in the United Kingdom of the exposure of operators to pesticide sprays were used to indicate the performance required of protective clothing. Laboratory tests, designed to simulate maximum levels of contamination, as far as practicable, were then applied to protective clothing materials and finished items to facilitate the development of national and international standards of performance. Studies of the relative efficiencies of protective garments in field spraying operations were also undertaken to assess the value of laboratory test data for the selection of effective spray suits.
High protection factors, based on the ratio of the amounts of spray chemical found on and inside the clothing, were usually recorded in the field studies. The correlation of performance data with laboratory test data was only fair. The laboratory tests of permeation and penetration posed high levels of contamination, however, and tended to err therefore on the side of safety in assessments of the potential efficiency of protective clothing.
Protection Offered by Lightweight Clothing Materials to the Heat of a Fire
Authors: Schoppee MM , Welsford JM , Abbott NJ 
Published: December 2008

Factors affecting the thermal performance of protective clothing are discussed in a general way, and a laboratory method of achieving heat absorption rates typical of those occurring during exposure to a large fire is described. Using this method, the strength retention of fabrics during short-term exposure at high heat flux levels has been found to depend on the temperature achieved at a given instant during exposure and to be independent of the mechanism of heat absorption. A comparison of the duration of exposure to high heat flux levels that causes various polymeric fabrics to lose most of their original strength or to autoignite predicts that such high-temperature materials as polybenzimidazole (PBI) and Nomex/Kevlar can provide a few extra seconds of protection against the extreme heat of a large fire.
Some difficulties associated with the use of an instrumented skin-simulant device for determining the rate of conductive heat transfer through fabrics of various kinds during standard gas flame impingement tests are also discussed. There is, at present, no accurate way to translate temperatures measured at a depth of 500 μm in a fabric-covered skin simulant to temperatures appropriate for a depth of 80 μm, the skin depth to which clinical data regarding tissue damage are related. Until the conductive heat flow equation can be revised, ranking of fabrics by the maximum temperature achieved in the skin simulant remains the only reliable method of using data from this device.
A Method for Testing Fabrics with Molten Metals
Authors: Jaynes PS 
Published: December 2008

This paper describes a method for testing fabrics with molten metals. The test evaluates the fabric's ability to protect people who are accidentally splashed by metals such as molten iron, aluminum, or brass.
Some test results are discussed to illustrate the application of the test method. The test procedure is substantially the same as a test method for evaluating heat transfer through materials upon contact with molten substances, now being developed by ASTM Subcommittee F23.80 on Molten Substances, a subcommittee of ASTM Committee F-23 on Protective Clothing.
U.S. Navy Protective Clothing Program
Authors: Audet NF , Spindola KJ 
Published: December 2008

The Navy Clothing and Textile Research Facility is involved in a major effort to develop fire retardant-heat protective clothing for Navy shipboard personnel encompassing both work and special protective clothing.
To determine the degree of protection afforded by the various articles of clothing being developed, both laboratory and field testing have been employed. Laboratory material tests have included vertical flammability resistance tests and protection time determinations for flame impingement exposure. Field tests have involved exposure of garments to total flame envelopment utilizing manikins equipped with paper tape temperature sensors to estimate the extent of burn injury sustained.
The usefulness of laboratory tests such as flame impingement tests to predict material/clothing performance under more realistic fire threat conditions is limited because of differences in exposure conditions between laboratory tests and full-scale fire tests. Laboratory tests do, however, provide an extremely useful screening tool to limit the number of candidate systems to be evaluated under field conditions.
This paper covers the nature of some of the clothing systems being developed, the laboratory and field evaluation procedures employed, and some of the laboratory and field test data accumulated on the materials and clothing items investigated.
The Development of Improved Forgings for Modern Steam Turbines
Authors: Curran RM 
Published: December 2008

This paper describes the developments that have taken place during the past 40 years in the manufacture of the large rotor forgings that are required for the turbine and generator sets in electric utility, central station applications. Modifications in steelmaking practices—such as the changes from open hearth to the electric practice, the introduction of vacuum pouring, and changes in ingot mold design—are discussed, as well as evaluations of newer remelt techniques such as vacuum consumable electrode melting, electroslag remelting, and electroslag hot topping. Changes in alloy content and heat-treating practices and the improvements that have resulted in the mechanical properties and fracture toughness are illustrated.
The progress that has been made in reducing the incidence of internal flaws and the improvements that have been made in nondestructive testing and evaluation to quantitatively appraise the effect of such flaws on the probable performance are discussed.
It is concluded that in low-pressure rotors, as a result of the improved cleanliness, detection methods, and fracture toughness, the probability of an undetected critical size defect has been decreased by several orders of magnitude. In the case of the high-temperature rotors, the improvements in properties, together with improved designs and operating procedures, have substantially improved the life expectancy of these rotors in spite of increases in forging size and unit ratings.
The important contributions that ASTM committees have made to this progress are described and acknowledged.
Influence of Advanced Steelmaking Technology on Specification Trends for Rotor Forgings
Authors: Steiner JE , Jaffee RI 
Published: December 2008

Advanced steelmaking equipment and processes that are state of the art for the production of rotor forgings are described. The Electric Power Research Institute (EPRI) has sponsored a study on high-pressure (HP) rotor forgings of 1Cr-Mo-V steel with 0.001 to 0.002% sulfur content produced by conventional vacuum carbon deoxidation (VCD) and electroslag remelting processes. Low phosphorus, low hydrogen, and residual element control were also objectives of this study.
Laboratory studies show that combined low levels of manganese (Mn), phosphorus (P), silicon (Si), and residual elements improve the toughness and resistance to temper embrittlement of rotor steels. In a recent EPRI program with Vereinigte Edelstahlwerke, the process combination basic electric arc furnace melting and ladle furnace refining with vacuum treatment successfully produced a 25-metric-ton model rotor in which levels of 0.02Mn, 0.002P, 0.001S, 0.04Si, and 0.005Al at 27 ppm oxygen were achieved.
Specification implications of these trends to high-purity rotor steels suggest that requirements for Mn, Si, and sulfur (S) will trend to lower content levels.