bluuebunny/crossref_metadata_2025 huggingface dataset:
Radical-Scavenging Activity and Cytotoxicity of p-Methoxyphenol and p-Cresol Dimers
Authors: Kadoma Yoshinori , Murakami Yukio , Ogiwara Takako , Machino Mamoru , Yokoe Ichiro , Fujisawa Seiichiro
Published: February 2010

Compoundswith two phenolic OH groups like curcumin possess efficient antioxidant and anti-inflammatory activity. We synthesized p-cresol dimer (2,2'-dihydroxy-5,5'-dimethylbiphenol, 2a) and p-methoxyphenol dimer (2,2'-dihydroxy-5,5'-dimethoxybiphenol, 2b) by ortho-ortho coupling reactions of the parent monomers, p-cresol (1a) and p-methoxyphenol (1b), respectively. Their antioxidant activity was determined using the induction period method, and their cytotoxicity towards RAW 264.7 cells was also investigated using a cell counting kit. The stoichiometric factors n (number of free radicals trapped by one mole of antioxidant moiety) for 2a and 2b were 3 and 2.8, respectively, being greater than those for 1a and 1b. The ratio of the rate constant of inhibition to that of propagation (kinh/kp) for 2a and 2b was similar to that for 2-t-butyl-4-methoxyphenol (BHA), a conventional food antioxidant. The 50% inhibitory dose (ID50) declined in the order 1b > 1a >> 2b > 2a > BHA. The cytotoxicity for 2a and 2b was significantly greater than that for the parent monomers (p < 0.001), but smaller than that for BHA (p < 0.01). Compounds 2a and 2b may be useful as food antioxidants.
Synthesis of Novel Aryl(heteroaryl)sulfonyl Ureas of Possible Biological Interest
Authors: Sączewski Franciszek , Kuchnio Anna , Samsel Monika , Łobocka Marta , Kiedrowska Agnieszka , Lisewska Karolina , Sączewski Jarosław , Gdaniec Maria , Bednarski Patrick J.
Published: February 2010

The course of reaction of aryl and heteroaryl sulfonamides with diphenylcarbonate (DPC) and 4-dimethylaminopyridine (DMAP) was found to depend on the pKa of the sulfonamide used. Aryl sulfonamides with pKa ~ 10 gave 4-dimethylamino-pyridinium arylsulfonyl-carbamoylides, while the more acidic heteroaryl sulfonamides (pKa ~ 8) furnished 4-dimethylaminopyridinium heteroarylsulfonyl carbamates. Both the carbamoylides and carbamate salts reacted with aliphatic and aromatic amines with the formation of appropriate aryl(heteroaryl)sulfonyl ureas, and therefore, can be regarded as safe and stable substitutes of the hazardous and difficult to handle aryl(heteroaryl)sulfonyl isocyanates.
Continuous Feedings of Fortified Human Milk Lead to Nutrient Losses of Fat, Calcium and Phosphorous
Authors: Rogers Stefanie P. , Hicks Penni D. , Hamzo Maria , Veit Lauren E. , Abrams Steven A.
Published: February 2010

Substantial losses of nutrients may occur during tube (gavage) feeding of fortified human milk. Our objective was to compare the losses of key macronutrients and minerals based on method of fortification and gavage feeding method. We used clinically available gavage feeding systems and measured pre- and post-feeding (end-point) nutrient content of calcium (Ca), phosphorus (Phos), protein, and fat. Comparisons were made between continuous, gravity bolus, and 30-minute infusion pump feeding systems, as well as human milk fortified with donor human milk-based and bovine milk-based human milk fortifier using an in vitro model. Feeding method was significantly associated with fat and Ca losses, with increased losses in continuous feeds. Fat losses in continuous feeds were substantial, with 40 ± 3 % of initial fat lost during the feeding process. After correction for feeding method, human milk fortified with donor milk-based fortifier was associated with significantly less loss of Ca (8 ± 4% vs. 28 ± 4%, p< 0.001), Phos (3 ± 4% vs. 24 ± 4%, p < 0.001), and fat (17 ± 2% vs. 25 ± 2%, p = 0.001) than human milk fortified with a bovine milk-based fortifier (Mean ± SEM).
Potential Health-modulating Effects of Isoflavones and Metabolites via Activation of PPAR and AhR
Authors: Medjakovic Svjetlana , Mueller Monika , Jungbauer Alois
Published: February 2010

Isoflavones have multiple actions on cell functions. The most prominent one is the activation of estrogen receptors. Other functions are often overlooked, but are equally important and explain the beneficial health effects of isoflavones. Isoflavones are potent dual PPARα/γ agonists and exert anti-inflammatory activity, which may contribute to the prevention of metabolic syndrome, atherosclerosis and various other inflammatory diseases. Some isoflavones are potent aryl hydrocarbon receptor (AhR) agonists and induce cell cycle arrest, chemoprevention and modulate xenobiotic metabolism. This review discusses effects mediated by the activation of AhR and PPARs and casts a light on the concerted action of isoflavones.
Effects of Spatial and Spectral Resolutions on Fractal Dimensions in Forested Landscapes
Authors: Al-Hamdan Mohammad , Cruise James , Rickman Douglas , Quattrochi Dale
Published: February 2010

Recent work has shown that more research is needed in applying fractal analysis to multi-resolution remote sensing data for landscape characterization. The purpose of this study was to closely examine the impacts that spatial and spectral resolutions have on fractal dimensions using real-world multi-resolution remotely sensed data as opposed to the more conventional single resolution and aggregation approach. The study focused on fractal analysis of forested landscapes in the southeastern United States and Central America. Initially, the effects of spatial resolution on the computed fractal dimensions were examined using data from three instruments with different spatial resolutions. Based on the criteria of mean value and variation within the accepted ranges of fractal dimensions, it was determined that 30-m Landsat TM data were best able to capture the complexity of a forested landscape in Central America compared to 4-m IKONOS data and 250-m MODIS data. Also, among the spectral bands of Landsat TM images of four national forests in the southeastern United States, tests showed that the spatial indices of fractal dimensions are much more distinguishable in the visible bands than they are in the near-mid infrared bands. Thus, based solely on the fractal analysis, the fractal dimensions could have relatively higher chances to distinguish forest characteristics (e.g., stand sizes and species) in the Landsat TM visible wavelength bands than in the near-mid infrared bands. This study has focused on a relative comparison between visible and near-mid infrared wavelength bands; however it will be important to study in the future the effect of a combination of those bands such as the Normalized Difference Vegetation Index (NDVI) on fractal dimensions of forested landscapes.
Detection of Vertical Pole-Like Objects in a Road Environment Using Vehicle-Based Laser Scanning Data
Authors: Lehtomäki Matti , Jaakkola Anttoni , Hyyppä Juha , Kukko Antero , Kaartinen Harri
Published: February 2010

Accurate road environment information is needed in applications such as road maintenance and virtual 3D city modelling. Vehicle-based laser scanning (VLS) can produce dense point clouds from large areas efficiently from which the road and its environment can be modelled in detail. Pole-like objects such as traffic signs, lamp posts and tree trunks are an important part of road environments. An automatic method was developed for the extraction of pole-like objects from VLS data. The method was able to find 77.7% of the poles which were found by a manual investigation of the data. Correctness of the detection was 81.0%.
Automatically Augmenting Lifelog Events Using Pervasively Generated Content from Millions of People
Authors: Doherty Aiden R. , Smeaton Alan F.
Published: February 2010

In sensor research we take advantage of additional contextual sensor information to disambiguate potentially erroneous sensor readings or to make better informed decisions on a single sensor’s output. This use of additional information reinforces, validates, semantically enriches, and augments sensed data. Lifelog data is challenging to augment, as it tracks one’s life with many images including the places they go, making it non-trivial to find associated sources of information. We investigate realising the goal of pervasive user-generated content based on sensors, by augmenting passive visual lifelogs with “Web 2.0” content collected by millions of other individuals.
Paper Actuators Made with Cellulose and Hybrid Materials
Authors: Kim Jaehwan , Yun Sungryul , Mahadeva Suresha K. , Yun Kiju , Yang Sang Yeol , Maniruzzaman Mohammad
Published: February 2010

Recently, cellulose has been re-discovered as a smart material that can be used as sensor and actuator materials, which is termed electro-active paper (EAPap). This paper reports recent advances in paper actuators made with cellulose and hybrid materials such as multi-walled carbon nanotubes, conducting polymers and ionic liquids. Two distinct actuator principles in EAPap actuators are demonstrated: piezoelectric effect and ion migration effect in cellulose. Piezoelectricity of cellulose EAPap is quite comparable with other piezoelectric polymers. But, it is biodegradable, biocompatible, mechanically strong and thermally stable. To enhance ion migration effect in the cellulose, polypyrrole conducting polymer and ionic liquids were nanocoated on the cellulose film. This hybrid cellulose EAPap nanocomposite exhibits durable bending actuation in an ambient humidity and temperature condition. Fabrication, characteristics and performance of the cellulose EAPap and its hybrid EAPap materials are illustrated. Also, its possibility for remotely microwave-driven paper actuator is demonstrated.
Chiral Symmetry Breaking Phenomenon Caused by a Phase Transition
Authors: Tamura Rui , Iwama Sekai , Takahashi Hiroki
Published: February 2010

We report the mechanism and scope of “preferential enrichment”, which is an unusual symmetry-breaking enantiomeric resolution phenomenon that is initiated by the solvent-assisted solid-to-solid transformation of a metastable polymorphic form into a thermodynamically stable one during crystallization from the supersaturated solution of certain kinds of racemic mixed crystals (i.e., solid solutions or pseudoracemates) composed of two enantiomers. The mechanism can well be interpreted in terms of a symmetrybreaking complexity phenomenon involving multistage processes that affect each other.
Isolation and characterization of microsatellite markers in the rare clonal plant, Spiraea virginiana (Rosaceae)
Authors: Brzyski Jessica R.
Published: February 2010

• Premise of the study: Microsatellite markers were developed in Spiraea virginiana, a federally threatened native shrub found along stream banks, to identify clonal genotypes and measure population genetic variability.

• Methods and Results: Eleven primer sets were developed using a non‐radioactive protocol. These revealed a moderate level of genetic variation, as indicated by the number of alleles per locus (range = 1–4) and an average observed heterozygosity of 0.595. Select loci also amplified successfully in the related species Spiraea japonica.

• Conclusion: Development of the markers described here is critical for the genetic identification of clonal plants as a first step in demographic analyses, and is necessary for the future conservation of this rare species. Amplification of the markers in S. japonica suggests their potential utility in research regarding this species.
Platelet-Rich Plasma: A Review of the Science and Possible Clinical Applications
Authors: Mehta Vishal
Published: February 2010

Educational Objectives

1.

Define the mechanism of action of platelet-rich plasma and how it is derived.

2.

Summarize the role of platelets in the healing cascade.

3.

Discuss animal and human data regarding platelet-rich plasma and tissue healing.

4.

List the potential clinical applications of platelet-rich plasma.
Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood‐onset systemic lupus erythematosus
Authors: Brunner Hermine I. , Higgins Gloria C. , Wiers Kristina , Lapidus Sivia K. , Olson Judyann C. , Onel Karen , Punaro Marilynn , Ying Jun , Klein‐gitelman Marisa S. , Giannini Edward H.
Published: February 2010

Objective

To prospectively validate the provisional criteria for the evaluation of response to therapy in children with systemic lupus erythematosus (SLE).

Methods

In this multicenter study, childhood‐onset SLE patients (n = 98; 81 girls, 17 boys, 50% white, 88% non‐Hispanic) were followed every 3 months for up to 7 visits (total number of visits 623). The 5 childhood‐onset SLE core response variables were obtained at the time of each visit: 1) physician assessment of overall disease activity, 2) parent assessment of patient well‐being, 3) Child Health Questionnaire, 4) proteinuria, and 5) global disease activity measure score, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). Physician‐rated relevant changes in the disease course (clinically relevant improvement, no change in disease, or worsening) between visits served as the criterion standard. Mixed models were used to assess the diagnostic accuracy of the 4 highest‐ranked provisional definitions of response to therapy.

Results

There were 89 episodes of clinically relevant improvement between 2 consecutive visits, and 448 episodes without improvement. Irrespective of the choice of the global disease activity measure (ECLAM, SLAM, SLEDAI), sensitivities of all 4 highest‐ranked definitions were low (all ≤31%), whereas their specificities were excellent (all >88%). Using logistic models, alternative definitions can be developed with both 80% sensitivity and specificity.

Conclusion

The provisional criteria of response to therapy in childhood‐onset SLE may have considerably lower sensitivity than previously reported. Additional validation in clinical trials is necessary to further evaluate the measurement properties of the provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology criteria for response to therapy in children with SLE.
Improvements in quality of life and functional status in patients with psoriatic arthritis receiving anti–tumor necrosis factor therapies
Authors: Saad Amr A. , Ashcroft Darren M. , Watson Kath D. , Symmons Deborah P. M. , Noyce Peter R. , Hyrich Kimme L. ,   British Society for Rheumatology Biologics Register
Published: February 2010

Objective

To evaluate the impact of anti–tumor necrosis factor (anti‐TNF) therapies on quality of life (QOL) and functional status in psoriatic arthritis (PsA) patients and study potential predictors for QOL improvements.

Methods

The study was based on a cohort of 596 PsA patients receiving anti‐TNF therapies. Changes in functional status and QOL were assessed using the Health Assessment Questionnaire (HAQ) and Short Form 36 (SF‐36) questionnaire on a 6‐month basis. The Short Form 6D (SF‐6D) was calculated as a utility score. Univariate and multivariate linear regression models were developed to examine potential predictors of QOL improvements at 6 months, using a range of demographic, baseline disease‐specific, and therapeutic variables.

Results

At 6 months, significant improvements in all SF‐36 subscale scores were found, with the greatest percentage improvement from baseline related to physical role (113.8%; 95% confidence interval [95% CI] 102.6, 125.0). The percent improvement for the physical component scale was 53.2% (95% CI 44.5, 61.9) at 6 months, whereas that for the mental component scale was 16.9% (95% CI 14.7, 19.2). The mean ± SD SF‐6D score was 0.58 ± 0.07 at baseline, and this improved to 0.63 ± 0.06 at 6 months. The median HAQ score at baseline was 1.88 (interquartile range [IQR] 1.38–2.25) for the entire cohort, and this improved to 1.25 (IQR 0.63–1.88) at 6 months. Improvements in Disease Activity Score in 28 joints at 6 months were found to be significantly associated with QOL improvements at the same time point.

Conclusion

Anti‐TNF therapy is associated with improvement in both physical and mental status in PsA patients. These improvements were most substantial in patients who also had improvements in their disease activity.
Dual‐Gate Organic Field‐Effect Transistors as Potentiometric Sensors in Aqueous Solution
Authors: Spijkman Mark‐Jan , Brondijk Jakob J. , Geuns Tom C. T. , Smits Edsger C. P. , Cramer Tobias , Zerbetto Francesco , Stoliar Pablo , Biscarini Fabio , Blom Paul W. M. , de Leeuw Dago M.
Published: February 2010

Buried electrodes and protection of the semiconductor with a thin passivation layer are used to yield dual‐gate organic transducers. The process technology is scaled up to 150‐mm wafers. The transducers are potentiometric sensors where the detection relies on measuring a shift in the threshold voltage caused by changes in the electrochemical potential at the second gate dielectric. Analytes can only be detected within the Debye screening length. The mechanism is assessed by pH measurements. The threshold voltage shift depends on pH as ΔVth = (Ctop/Cbottom) × 58 mV per pH unit, indicating that the sensitivity can be enhanced with respect to conventional ion‐sensitive field‐effect transistors (ISFETs) by adjusting the ratio of the top and bottom gate capacitances. Remaining challenges and opportunities are discussed.
Enhanced Fluorescence Microscopic Imaging by Plasmonic Nanostructures: From a 1D Grating to a 2D Nanohole Array
Authors: Cui Xiaoqiang , Tawa Keiko , Kintaka Kenji , Nishii Junji
Published: February 2010

A two‐dimensional (2D) plasmonic coupling nanostructure for enhanced fluorescence observation using a microscope is presented. The substrate contained periodically assembled nanohole arrays with a pitch of 400 nm and a depth of 25 nm. In comparison with one‐dimensional (1D) gratings, this new substrate presented an excellent surface plasmon coupling ability to illuminate light from all directions. Under an optical microscope, an enhancement in the fluorescence intensity of up to 100 times compared with a plain glass slide was observed. The ability to markedly increase the fluorescence intensity means this technique has great potential for application in biodiagnostics, imaging, sensing, and photovoltaic cells.
DNA Sensing Using Nanocrystalline Surface‐Enhanced Al2O3 Nanopore Sensors
Authors: Venkatesan Bala Murali , Shah Amish B. , Zuo Jian‐Min , Bashir Rashid
Published: February 2010

A new solid‐state, Al2O3 nanopore sensor with enhanced surface properties for the real‐time detection and analysis of individual DNA molecules is reported. Nanopore formation using electron‐beam‐based decomposition transforms the local nanostructure and morphology of the pore from an amorphous, stoichiometric structure (O to Al ratio of 1.5) to a heterophase crystalline network, deficient in O (O to Al ratio of ≈0.6). Direct metallization of the pore region is observed during irradiation, thereby permitting the potential fabrication of nanoscale metallic contacts in the pore region with application to nanopore‐based DNA sequencing. Dose‐dependent phase transformations to purely γ and/or α‐phase nanocrystallites are also observed during pore formation, allowing for surface‐charge engineering at the nanopore/fluid interface. DNA transport studies reveal an order‐of‐magnitude reduction in translocation velocities relative to alternate solid‐state architectures, accredited to high surface‐charge density and the nucleation of charged nanocrystalline domains. The unique surface properties of Al2O3 nanopore sensors make them ideal for the detection and analysis of single‐stranded DNA, double‐stranded DNA, RNA secondary structures, and small proteins. These nanoscale sensors may also serve as useful tools in studying the mechanisms driving biological processes including DNA–protein interactions and enzyme activity at the single‐molecule level.
Dual‐Function Scattering Layer of Submicrometer‐Sized Mesoporous TiO2 Beads for High‐Efficiency Dye‐Sensitized Solar Cells
Authors: Huang Fuzhi , Chen Dehong , Zhang Xiao Li , Caruso Rachel A. , Cheng Yi‐Bing
Published: February 2010

Submicrometer‐sized (830 ± 40 nm) mesoporous TiO2 beads are used to form a scattering layer on top of a transparent, 6‐µm‐thick, nanocrystalline TiO2 film. According to the Mie theory, the large beads scatter light in the region of 600–800 nm. In addition, the mesoporous structure offers a high surface area, 89.1 m2 g−1, which allows high dye loading. The dual functions of light scattering and electrode participation make the mesoporous TiO2 beads superior candidates for the scattering layer in dye‐sensitized solar cells. A high efficiency of 8.84% was achieved with the mesoporous beads as a scattering layer, compared with an efficiency of 7.87% for the electrode with the scattering layer of 400‐nm TiO2 of similar thickness.
Erythrocyte C3d and C4d for monitoring disease activity in systemic lupus erythematosus
Authors: Kao Amy H. , Navratil Jeannine S. , Ruffing Margie J. , Liu Chau‐Ching , Hawkins Douglas , McKinnon Kathleen M. , Danchenko Natalya , Ahearn Joseph M. , Manzi Susan
Published: February 2010

Objective

Disease activity in systemic lupus erythematosus (SLE) is typically monitored by measuring serum C3 and C4. However, these proteins have limited utility as lupus biomarkers, because they are substrates rather than products of complement activation. The aim of this study was to evaluate the utility of measuring the erythrocyte‐bound complement activation products, erythrocyte‐bound C3d (E‐C3d) and E‐C4d, compared with that of serum C3 and C4 for monitoring disease activity in patients with SLE.

Methods

The levels of E‐C3d and E‐C4d were measured by flow cytometry in 157 patients with SLE, 290 patients with other diseases, and 256 healthy individuals. The patients with SLE were followed up longitudinally. Disease activity was measured at each visit, using the validated Systemic Lupus Activity Measure (SLAM) and the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results

At baseline, patients with SLE had higher median levels of E‐C3d and E‐C4d (P < 0.0001) in addition to higher within‐patient and between‐patient variability in both E‐C3d and E‐C4d when compared with the 2 non‐SLE groups. In a longitudinal analysis of patients with SLE, E‐C3d, E‐C4d, serum C3, and anti–double‐stranded DNA (anti‐dsDNA) antibodies were each significantly associated with the SLAM and SELENA–SLEDAI. In a multivariable analysis, E‐C4d remained significantly associated with these SLE activity measures after adjusting for serum C3, C4, and anti‐dsDNA antibodies; however, E‐C3d was associated with the SLAM but not with the SELENA–SLEDAI.

Conclusion

Determining the levels of the erythrocyte‐bound complement activation products, especially E‐C4d, is an informative measure of SLE disease activity as compared with assessing serum C4 levels and should be considered for monitoring disease activity in patients with SLE.
Autoimmune diseases in women with Turner's Syndrome
Authors: Jørgensen Kristian T. , Rostgaard Klaus , Bache Iben , Biggar Robert J. , Nielsen Nete M. , Tommerup Niels , Frisch Morten
Published: February 2010

Objective

In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with Turner's syndrome is characterized by diseases with a female or male predominance.

Methods

Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798 Danish women with Turner's syndrome followed up for 12,461 person‐years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk.

Results

The overall risk of autoimmune disease among women with Turner's syndrome was twice that among Danish women in general (SIR 2.1 [95% CI 1.6–2.7]). For autoimmune diseases with a female predominance, the SIR among women with Turner's syndrome was 1.7 (95% CI 1.2–2.4), whereas the SIR for autoimmune diseases with a male predominance among these women was 3.9 (95% CI 2.5–5.8). Associations were strongest for Hashimoto thyroiditis (SIR 14.6 [95% CI 6.7–27.1]), a strongly female‐predominant condition, and type 1 diabetes mellitus (SIR 4.1 [95% CI 2.5–6.3]).

Conclusion

Women with Turner's syndrome are at excess risk of autoimmune diseases, notably autoimmune diseases characterized by male predominance.
Evidence of epistasis between TNFRSF14 and TNFRSF6B polymorphisms in patients with rheumatoid arthritis
Authors: Perdigones Nieves , Vigo Ana G. , Lamas José R. , Martínez Alfonso , Balsa Alejandro , Pascual‐Salcedo Dora , de la Concha Emilio G. , Fernández‐Gutiérrez Benjamín , Urcelay Elena
Published: February 2010

Objective

Genetic variants located close to 2 genes codifying for members of the tumor necrosis factor receptor superfamily (TNFRSF), TNFRSF14 and TNFRSF6B, have recently been associated with rheumatoid arthritis (RA) and with inflammatory bowel disease susceptibility, respectively. The TNFRSF6B protein has been related to osteoclastic activity, apoptosis inhibition, and modulation of T cell activation and differentiation. Interestingly, peptides encoded by both genes bind a common ligand called LIGHT, which is overexpressed in RA synovium. The aim of this study was to investigate the combined effect of the TNFRSF14 rs6684865 and TNFRSF6B rs4809330 polymorphisms in RA predisposition.

Methods

TaqMan genotyping of these polymorphisms was conducted in 649 patients with RA and 553 ethnically matched control subjects (first study). To validate the results, an independent replication cohort with 211 patients and 255 control subjects was additionally studied (replication study).

Results

The frequency of the rs6684865 G allele in the RA subgroup with the rs4809330 GG susceptibility genotype was significantly higher than that in the other patients with RA (74% versus 65%; P = 0.002) or in control subjects (74% versus 67%; P = 0.003). Because no significant differences between the control and patient groups in the first and replication studies were observed, the data were pooled. When compared with control subjects overall, the effect of the rs6684865 G allele in the group with the rs4809330 GG genotype (odds ratio [OR] 1.49) was significantly different from the effect observed in the group carrying the rs4809330 A allele (OR 0.97; P = 0.0015 by Breslow‐Day test of homogeneity).

Conclusion

We have identified and replicated a novel gene–gene interaction between 2 polymorphisms of TNFRSF members in Spanish patients with RA, based on the hypothesis of shared pathogenic pathways in complex diseases.
Adeno‐associated virus type 5–mediated intraarticular administration of tumor necrosis factor small interfering RNA improves collagen‐induced arthritis
Authors: Khoury Maroun , Courties Gabriel , Fabre Sylvie , Bouffi Carine , Seemayer Christian A. , Vervoordeldonk Margriet J. , Tak Paul P. , Jorgensen Christian , Apparailly Florence
Published: February 2010

Objective

RNA interference (RNAi) is a powerful tool for sequence‐specific gene silencing, and interest in its application in human diseases is growing. Given the success of recent strategies for administering gene therapy in rheumatoid arthritis using recombinant vectors such as adeno‐associated virus type 5 (rAAV5) for optimized intraarticular gene transfer, we undertook the present study to determine the feasibility of using rAAV5‐mediated RNAi‐based therapy in arthritis.

Methods

We developed rAAV5 vectors expressing short hairpin small interfering RNA (shRNA) against tumor necrosis factor α (TNFα) under H1 promoter, and carrying the enhanced green fluorescent protein (eGFP) reporter gene under cytomegalovirus promoter (rAAV5‐shTNF). TNFα gene silencing was validated in vitro with mouse macrophages. Mice with collagen‐induced arthritis were injected in the ankle and knee joints, at disease onset, with either rAAV5‐shTNF or control rAAV5‐eGFP vectors (5 × 109 particles). Arthritis severity was assessed clinically and histologically, and immunologic response was examined. Local and systemic transgene expression was monitored using quantitative reverse transcriptase–polymerase chain reaction, immunohistochemical analysis, and enzyme‐linked immunosorbent assay.

Results

After a single injection of rAAV5‐shTNF into inflamed joints, local TNFα gene silencing provided rapid and long‐term suppression of arthritis progression and reduced joint damage compared with that observed in control groups. Treatment with rAAV5‐shTNF was associated with decreased proliferation and interferon‐γ production by antigen‐stimulated T cells from draining lymph nodes, and the potency of this treatment was similar to that observed with other treatment strategies targeting TNFα at the protein level, either locally or systemically.

Conclusion

Our data present the first proof‐of‐concept for the application of rAAV5‐mediated RNAi‐based gene therapy for local blockade of inflammation in experimental arthritis.
Utilizing a home‐based parent training approach in the treatment of food selectivity
Authors: Najdowski Adel C. , Wallace Michele D. , Reagon Kara , Penrod Becky , Higbee Thomas S. , Tarbox Jonathan
Published: February 2010

Evaluating effects of utilizing parents as therapists for treating behavior problems has become increasingly important in the dissemination and practice of applied behavior analysis. However, home‐based parent training approaches have been underused in treating feeding problems. In this study, mothers were trained to implement differential reinforcement of alternative behavior (DRA) combined with non‐removal of the spoon and demand fading for the treatment of their childrens' food selectivity. The procedures were highly effective and generalization to untargeted foods was observed. Parent procedural integrity and parent collected interobserver agreement (IOA) data remain high throughout the study. This study also demonstrated an effective method for systematically decreasing reinforcement magnitude and schedules in an effort to mimic traditional reinforcer delivery such as intermittently providing a dessert at the end of the meal. Finally, this study successfully increased a demand fading ratio of 50–150% without noticeable side effects. Copyright © 2010 John Wiley & Sons, Ltd.
Does family interrelating change over the course of individual treatment?
Authors: Kalaitzaki Argyroula , Birtchnell John , Nestoros Joannis
Published: February 2010

Interrelating is a combination of each person's relating towards a specified other and each person's view of the other's relating towards him/her. Negative interrelating is a maladaptive form of interrelating. The study aims to (1) compare the negative interrelating within the families of neurotic and psychotic psychotherapy outpatients; (2) examine whether individual treatment has a beneficial effect upon negative interrelating; (3) examine whether the improvement extends beyond the patients' interrelating with their parents (i.e., between the parents and the patients' sibling and between the parents themselves); and (4) make similar comparisons within a sample of non‐patients. The negative interrelating between the psychotic patients and their parents was more marked than that between the neurotic patients and their parents. The negative interrelating between the patients and their parents dropped significantly over the course of therapy. There were also significant changes in the interrelating between the patients' siblings and their parents and between the parents themselves even though they had not been involved in the therapy. Many of the end of therapy scores of the patients and their parents approached more those of the non‐patients. Copyright © 2010 John Wiley & Sons, Ltd.

Key Practitioner Message:

• It is useful to measure both the negative relating of patients and the negative interrelating between patients and other family members.

• The patients' therapy appears also to benefit the interrelating between those family members who were not involved in the therapy.

• These findings may be more marked in Greek families, in which young adults stay closer to their parents.
Decode‐and‐forward with partial relay selection
Authors: Rui Xianyi
Published: February 2010

Exact expressions for outage probability and symbol error rate are presented for a decode‐and‐forward cooperative network with partial relay selection. An independent but not identically distributed Nakagami‐m fading environment is considered. Numerical and simulated results show the validity of the analytical results. Copyright © 2010 John Wiley & Sons, Ltd.
Energieeffizient und erdbebensicher Bauen mit monolithischem Ziegelmauerwerk
Authors: Butenweg Christoph , Fäcke Andreas , Fehling Ekkehard , Gellert Christoph , Gierga Michael , Meyer Udo , Rütschlin Andreas H. , Stürz Jochen
Published: February 2010

Moderne Bauwerke müssen heute eine hohe energetische Leistungsfähigkeit aufweisen und gleichzeitig alle einwirkenden Lasten sicher abtragen. Dies stellt insbesondere in Erdbebengebieten hohe Anforderungen an die verwendeten Baustoffe. Am baupraktischen Beispiel einer Doppelhaushälfte wird demonstriert, dass die Symbiose aus energieeffizientem und gleichzeitig erdbebensicherem Bauen in der höchsten deutschen Erdbebenzone mit monolithischem Ziegelmauerwerk gut realisierbar ist. Als Ziegelmauerwerk werden für die Außenwände wärmetechnisch optimierte Hochlochziegel verwendet, die sowohl die Anforderungen der Energieeinsparverordnung 2009 als auch die Anforderungen an Mauerwerkbaustoffe nach den aktuellen Erdbebennormen erfüllen. Der Erdbebennachweis der Doppelhaushälfte erfolgt mit einem nichtlinearen Nachweisverfahren, das für eine einfache praktische Anwendung programmtechnisch umgesetzt wurde. Für den Nachweis wurden aus zyklischen Schubwandversuchen ermittelte Last‐Verformungskurven verwendet. Das gesamte in Deutschland noch nicht normativ geregelte Nachweiskonzept wurde im Rahmen einer Zustimmung im Einzelfall geprüft und genehmigt.

Energy‐efficient and earthquake‐proof building with monolithic brickwork. Nowadays, modern buildings need to have a high energetic performance and they have to withstand seismic actions at the same time. These contradictory demands can only be fulfilled by construction materials of high quality and optimal performance. On the example of a semi‐detached building in Germany’s highest earthquake‐zone it is demonstrated that buildings made of monolithic brickwork meet all the requirements of energy efficiency and earthquake resistant design. The monolithic brickwork was carried out with thermo technical optimized vertical perforated bricks for the external walls. The used brick type fulfils all demands according to DIN 4149 and EnEV 2009. The structural safety of the semi‐detached building is verified by means of nonlinear deformation based method, which has been implemented into a user friendly software package. The pushover curves of the single shear walls are determined by cyclic shear wall tests. The procedure is not part of the German earthquake code yet and has been approved by national building authorities.
Synthesis of N‐Bz‐Protected D‐Daunosamine and D‐Ristosamine by Silica Gel Promoted Intramolecular Conjugate Addition of Trichloroacetimidates obtained from Osmundalactone and Its Epimer
Authors: Matsushima Yoshitaka , Kino Jun
Published: February 2010

Trichloroacetimidates prepared from osmundalactone and its epimer unexpectedly undergo intramolecular conjugate addition during silica gel chromatography to produce oxazolines in excellent yields. The novel, simple synthesis of N‐Bz‐protected D‐daunosamine and D‐ristosamine from these oxazolines is described in this paper.
Polymer‐Supported Synthesis of Oligosaccharides Using a Diisopropylsiloxane Linker and Trichloroacetimidate Donors
Authors: Mar Kayser M. , de Paz José L. , Nieto Pedro M.
Published: February 2010

We describe herein the polymer‐supported synthesis of biologically relevant oligosaccharides using a diisopropylsiloxane linker and trichloroacetimidates as glycosyl donors. Siloxane linkers offer important advantages over closely related silyl ethers since even sterically hindered alcohols can be directly loaded onto commercially available polymers, such as soluble polyethylene glycol (PEG), without prior manipulation of the support. Final products can be easily detached by mild fluoridolysis to afford OH‐tagged sugar probes. We followed an acceptor‐bound approach that fixed the nucleophile on the polymer, and we selected soluble PEG as the support due to higher reactivity of bound sugars and easy reaction monitoring. Following this strategy, the trisaccharide repeating unit of the capsular polysaccharide of Neisseria meningitidis (serogroup L) and the disaccharide containing the structural motif of hyaluronic acid were successfully synthesized.
Parathyroid hormone is not required for normal milk composition or secretion or lactation-associated Bone loss in normocalcemic Rats
Authors: Garner Sanford C. , Boass Agna , Toverud Svein U.
Published: February 2010

To determine if parathyroid hormone (PTH) is essential for lactation in rats, the parathyroid glands were removed surgically during the first week of lactation and the rats were given a diet containing a high calciumphosphorus ratio to maintain a normal serum calcium concentration. Lactating rats were placed on diet containing 1.2% calcium (Ca) and 0.8, 0.6, or 0.4% phosphorus (P) on day 2 postpartum (PP) and were parathyroidectomized (PTX) at 4–6 days PP. At 10 days PP serum Ca was 10.5 ± 0.2 mg/dl (mean ± SEM) for PTX rats and 10.4 ± 0.3 mg/dl in sham-operated lactating rats when the diet contained 0.6% P. When the diet P was 0.8%, the litters gained little or no weight and serum Ca fell to 6.9 ± 0.6 mg/dl by day 10 PP in PTX rats compared with 10.2 ± 0.2 mg/dl in sham rats. PTX rats fed the diet containing 1.2% Ca and 0.6% P maintained a normal serum Ca level until at least day 18 PP, but their serum P levels fell gradually from approximately 5 mg/dl at 10 days to 3 mg/dl at 18 days PP. In spite of this hypophosphatemia, the litters of PTX and sham rats had gained the same amount of weight by age 16 days, indicating equal milk production in the two groups. Milk Ca, P, and total solids were not significantly different between PTX and sham rats on day 11 PP. With the 1.2% Ca and 0.4% P diet, the femurs lost approximately 20% of dry bone mass in both PTX and sham rats (p < 0.01) between 5 days PP, when PTX was carried out, and 20 days PP. We conclude that the absence of the parathyroid glands does not affect milk production, milk mineral composition, or the lactation-associated bone loss when normal serum Ca levels are maintained by diet. We suggest that PTH is not essential for lactation beyond its normal function of maintaining the serum Ca concentration
Journal of Bone and Mineral Research
Authors: Devogelaer Jean-Pierre , De Deuxchaisnes Charles Nagant , Stein Frédéric
Published: February 2010

The gastrointestinal absorption of enteric-coated (EC) tablets of sodium fluoride (NaF) with respect to different time schedules of administration of calcium supplements in solution was tested. It was found that the simultaneous administration of these two medications under these formulations did not interfere with fluoride absorption. The calcium was also well absorbed as shown by the rise in serum ionized calcium concentration. Other schedules were studied as well, such as EC NaF tablets taken 1 hour after or 3 hours before the administration of calcium supplements. No superiority was shown, on the contrary, compared with the simultaneous administration of both medications. It was concluded that EC tablets of NaF and calcium supplements in solution can be provided simultaneously to enhance compliance.
Journal of Bone and Mineral Research
Authors: Kopp Jeffrey B. , Robey Pamela Gehron
Published: February 2010

Sodium fluoride has been shown to be effective therapy for some patients with vertebral osteoporosis. Data from histomorphometric studies in patients and animals suggest that at least part of this effect may be a consequence of a proliferative effect of fluoride, either direct or indirect, on the osteoblast or on an osteoblastic precursor cell. Experiments with osteoblastic cells derived from embryonic chick calvaria have demonstrated a mitogenic effect of fluoride. The present study examined whether fluoride affects in a similar way fetal human bone cells derived from femur or calvaria. Under a variety of culture conditions, including medium supplemented with serum and in serum-free medium, fluoride did not alter the proliferative rate of human bone cells as measured by thymidine incorporation and direct cell counting.
Journal of Bone and Mineral Research
Authors: DR. Murray T. M. , Harrison J. E. , Bayley T. A. , Josse R. G. , Sturtridge W. C. , Chow R. , Budden F. , Laurier L. , Pritzker K. P. H. , Kandel R. , Vieth R. , Strauss A. , Goodwin S.
Published: February 2010

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% ± 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p < 0.01), serum fluoride (r = 0.50, p < 0.01), and age (0.39, p < 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p < 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = −0.52, p < 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy. Only 18% of patients did not respond with an increase in bone mineral. These patients had significantly lower serum fluoride levels, and were significantly younger, with better renal function. The data suggest that younger patients may need a somewhat higher dose of fluoride to achieve the same effect. Side effects were tolerable for most patients. Gastrointestinal (GI) side effects were significantly reduced by the use of an enteric-coated preparation; very mild, transient GI side effects occurred in 11.1% of patients so treated. Transient lower extremity pain occurred in 9 patients (14.7%), and an additional 4 patients had transient symptoms from lower extremity stress fractures. Another 7 patients had femoral neck fractures during treatment. NaF causes a sustained, long-term increase in bone mineral with acceptable side effects in most patients. The dose of fluoride should be optimized individually for each patient on the basis of serum fluoride > 5 μmol/liter), histological effects of fluoride (or bone fluoride), and toxicity. The mean dose of enteric-coated tablets required to achieve a histologic fluoride effect (hyperosteoidosis) in 88% of patients so treated was 42.6 mg/day (19.3 mg elemental fluoride).
Journal of Bone and Mineral Research
Authors: Code R. Fraser , Mcneill Kenneth G. , Harrison Joan E.
Published: February 2010

We have developed a localized noninvasive nuclear magnetic resonance (NMR) method for determining the accumulated bone fluoride content in human index fingers. Using a 27 MHz “split-ring” resonator probe, we measure the total fluoride (F) content within a 6.5 cm length of the distal end of the index finger from a calibrated determination of the intensity of the observed 19F free induction decay (FID) signal. Since fluoride impurities accumulate almost exclusively in bone mineral, the 19F resonance signal is broadened by rigid lattice magnetic dipole–dipole interactions, causing the FID signal to have a relatively short lifetime of approximately 75μs. This short signal lifetime, plus the weakness of the signal strength prevents conventional magnetic resonance imaging equipment from observing the 19F in bone mineral. Nevertheless, we have achieved an in vivo sensitivity of ± 0.5 mg fluoride in an observation period of 30 min. Assuming an index finger has between 0.25 and 0.5 g of bone calcium, this sensitivity is just sufficient to detect fluorides in the index finger of most adults whose bone fluoride concentration is greater than 2.0 mg fluoride/g calcium (0.8 mg/g ash weight). We are particularly interested in using this new NMR technique to monitor the rate of bone fluoride accumulation in osteoporotic patients receiving therapeutic levels of fluoride in their diets.
Journal of Bone and Mineral Research
Authors: DR. Bayley T. A. , Muller C. , Harrison J. , Basualdo J. , Sturtridge W. , Josse R. , Murray T. M. , Pritzker K. P. H. , Vieth R. , Goodwin S. , Strauss A.
Published: February 2010

Twenty-two patients with steroid-induced osteoporosis were studied retrospectively to assess the effects on bone mass of fluoride therapy over 4 years. Thirteen of 19 patients with miscellaneous disorders and 2 with Cushing's syndrome received 1 g calcium/day, 50,000 IU vitamin D (D) weekly, and 40–60 mg/day sodium fluoride (F). Six patients with miscellaneous disorders and one with Cushing's syndrome received only Ca and vitamin D. The mean (±SD) cumulative dose of prednisone for fluoride-treated patients at the beginning of the study was 42 ± 25 g, and for those patients treated with only Ca and vitamin D, 45 ± 47 g, and during the study the cumulative dose was comparable in both groups. The bone mineral mass of the central skeleton was measured by neutron activation analysis and the results expressed as the calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75–1.2). In the 13 patients with miscellaneous disorders treated with fluoride, the mean ± SD CaBI rose from 0.65 ± .03 to 0.75 ± .03 after 3 years p < 0.001) and to 0.81 ± .11 at 4 years. Patients without fluoride had an initial mean CaBI of 0.70 ± .08 and it was not significantly changed over 3 years, 0.68 ± .09 and 4 years, 0.71 ± .09. The rise in CaBI in fluoride-treated patients with steroid-induced osteoporosis including Cushing's syndrome was comparable to that of 61 patients with postmenopausal osteoporosis treated with fluoride. In steroid osteoporotic patients treated with fluoride, fractures occurred in the first 2 years when the CaBI was still quite low. The results indicate that long-term fluoride therapy significantly increases bone mass in patients with steroid-induced osteoporosis to a similar degree as in patients with postmenopausal osteoporosis.