bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic toxicology in the 21st century: Reflections and future directions
Authors: Mahadevan Brinda , Snyder Ronald D. , Waters Michael D. , Benz R.Daniel , Kemper Raymond A. , Tice Raymond R. , Richard Ann M.
Published: April 2011

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high‐throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.
Statistical inference in Lombard's smooth‐change model
Authors: Quessy Jean‐François , Favre Anne‐Catherine , Saïd Mériem , Champagne Maryse
Published: April 2011

The sample properties of various inference procedures in Lombard's smooth‐change model are studied in this work. In particular, the power of six test statistics for the detection of change‐points in the mean and the variance of a series of independent observations is investigated under several alternatives. The robustness of the procedures under heterogeneity and serial dependence is considered as well. An investigation of the efficiency of an estimator of the change‐points is also presented. Conditional on these estimated change‐points, least squares estimators of the means in Lombard's model are derived and their efficiency is carefully studied. The procedures are illustrated on two environmental data sets, namely the annual volume of discharge from the Nile River and the annual temperature anomalies for the northern hemisphere. It will be seen that Lombard's model is flexible, that the test statistics of Lombard (1987) are powerful, and that the proposed estimators have nice properties; hence Lombard's model has a high potential for applications in the environmental sciences. Copyright © 2011 John Wiley & Sons, Ltd.
Textile heat release properties measured by microscale combustion calorimetry: experimental repeatability
Authors: Yang Charles Q. , He Qingliang
Published: April 2011

In this research, we evaluated the repeatability of microscale combustion calorimetry (MCC) measurement of heat release properties for different textile fabrics including polypropylene, cotton, polyester, Kevlar, acrylic, nylon, silk, and the cotton treated with an organophosphorus flame retardant. The repeatability investigation was mostly based on the measurement of peak heat release rate (PHRR) and heat release capacity (HRC), the two most important heat release parameters measured by MCC. We found that PHRR and HRC of most textile fibers had coefficient of variance (CV) lower than and in the vicinity of 3.0. The CVs were influenced by both the standard deviation (SD) of measurements and by the values of these measurements. The use of an aerobic pyrolysis environment (80/20 nitrogen/oxygen) for MCC experiments did not affect the repeatability of measurement. We also evaluated the shift of the oxygen analyzer as a result of long‐term usage, and found that PHRR and HRC of cotton decreased between−4.0 and−3.9, respectively, after an 11‐month period, indicating that the shift of the oxygen analyzer is limited. Experimental factors influencing the MCC repeatability were also discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Hepatitis C virus–infected women have a higher risk of advanced fibrosis and graft loss after liver transplantation than men
Authors: Lai Jennifer C. , Verna Elizabeth C. , Brown Robert S. , O'Leary Jacqueline G. , Trotter James F. , Forman Lisa M. , Duman Jeffrey D. , Foster Richard G. , Stravitz Todd R. , Terrault Norah A.
Published: April 2011

In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether female sex influences outcomes of HCV in the posttransplantation setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at five United States transplantation centers were included. The primary outcome was development of advanced disease, defined as biopsy-proven bridging fibrosis or cirrhosis. Secondary outcomes included death, graft loss, and graft loss with advanced recurrent disease. A total of 1,264 patients were followed for a median of 3 years (interquartile range, 1.8-4.7), 304 (24%) of whom were women. The cumulative rate of advanced disease at 3 years was 38% for women and 33% for men (

P

= 0.31), but after adjustment for recipient age, donor age, donor anti-HCV positivity, posttransplantation HCV treatment, cytomegalovirus infection and center, female sex was an independent predictor of advanced recurrent disease (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.02-1.70;

P

= 0.04). Among women, older donor age and treated acute rejection were the primary predictors of advanced disease. The unadjusted cumulative 3-year rates of patient and graft survival were numerically lower in women (75% and 74%, respectively) than men (80% and 78%, respectively), and in multivariable analyses, female sex was an independent predictor for death (HR, 1.30; 95% CI, 1.01-1.67;

P

= 0.04) and graft loss (HR, 1.31; 95% CI, 1.02-1.67;

P

= 0.03).

Conclusion:

Female sex represents an underrecognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and posttransplantation therapeutics can equalize HCV-specific outcomes in women and men. (Hepatology 2011;)
Effects of irrigation withdrawals on streamflows in a karst environment: lower Flint River Basin, Georgia, USA
Authors: Rugel Kathleen , Jackson C. Rhett , Romeis J. Joshua , Golladay Stephen W. , Hicks David W. , Dowd John F.
Published: April 2011

Extensive implementation of centre pivot irrigation systems occurred between 1970 and 1980 in the lower Flint River Basin (FRB) of southwestern Georgia, USA. Groundwater within this karstic system is in direct hydraulic connection with regional streams, many of which are incised through the overburden into underlying limestone. We used long‐term U.S. Geological Survey gaging station data to evaluate multiple flow metrics of two tributaries (Ichawaynochaway Creek and Spring Creek) in the lower FRB to determine the extent of changes in stream behaviour since irrigation practices intensified. We compared pre‐ and post‐irrigation flow duration curves, 1‐, 7‐, and 14‐day minimum flows, and 8‐day (seasonal) and annual baseflow recession slopes, in addition to evaluating regional climate data to determine whether significant differences existed between the pre‐ and post‐irrigation periods. Our results showed significant changes in low‐flow durations in the post‐irrigation record for both gages, including a decrease by an order of magnitude for 98% exceedance flows at Spring Creek. Both gages indicated significant reductions in 1‐, 7‐, and 14‐day low flows. Eight‐day baseflow recession curves (within early summer months) and annual baseflow recession curves became significantly steeper during the post‐irrigation period for Ichawaynochaway Creek. We also found that a significant relationship existed between winter and summer minimum flows in both streams in the pre‐irrigation period which was disrupted in post‐irrigation years. Regional climate data for the study period revealed no significant changes in rainfall totals or frequency of drought; however, there was evidence for a shift in seasonal rainfall patterns. Copyright © 2011 John Wiley & Sons, Ltd.
Explaining differences between bioaccumulation measurements in laboratory and field data through use of a probabilistic modeling approach
Authors: Selck Henriette , Drouillard Ken , Eisenreich Karen , Koelmans Albert A , Palmqvist Annemette , Ruus Anders , Salvito Daniel , Schultz Irv , Stewart Robin , Weisbrod Annie , van den Brink Nico W , van den Heuvel-Greve Martine
Published: April 2011

In the regulatory context, bioaccumulation assessment is often hampered by substantial data uncertainty as well as by the poorly understood differences often observed between results from laboratory and field bioaccumulation studies. Bioaccumulation is a complex, multifaceted process, which calls for accurate error analysis. Yet, attempts to quantify and compare propagation of error in bioaccumulation metrics across species and chemicals are rare. Here, we quantitatively assessed the combined influence of physicochemical, physiological, ecological, and environmental parameters known to affect bioaccumulation for 4 species and 2 chemicals, to assess whether uncertainty in these factors can explain the observed differences among laboratory and field studies. The organisms evaluated in simulations including mayfly larvae, deposit-feeding polychaetes, yellow perch, and little owl represented a range of ecological conditions and biotransformation capacity. The chemicals, pyrene and the polychlorinated biphenyl congener PCB-153, represented medium and highly hydrophobic chemicals with different susceptibilities to biotransformation. An existing state of the art probabilistic bioaccumulation model was improved by accounting for bioavailability and absorption efficiency limitations, due to the presence of black carbon in sediment, and was used for probabilistic modeling of variability and propagation of error. Results showed that at lower trophic levels (mayfly and polychaete), variability in bioaccumulation was mainly driven by sediment exposure, sediment composition and chemical partitioning to sediment components, which was in turn dominated by the influence of black carbon. At higher trophic levels (yellow perch and the little owl), food web structure (i.e., diet composition and abundance) and chemical concentration in the diet became more important particularly for the most persistent compound, PCB-153. These results suggest that variation in bioaccumulation assessment is reduced most by improved identification of food sources as well as by accounting for the chemical bioavailability in food components. Improvements in the accuracy of aqueous exposure appear to be less relevant when applied to moderate to highly hydrophobic compounds, because this route contributes only marginally to total uptake. The determination of chemical bioavailability and the increase in understanding and qualifying the role of sediment components (black carbon, labile organic matter, and the like) on chemical absorption efficiencies has been identified as a key next steps. Integr Environ Assess Manag 2012;8:42–63. © 2011 SETAC
Comparing laboratory- and field-measured biota–sediment accumulation factors
Authors: Burkhard Lawrence P , Arnot Jon A , Embry Michelle R , Farley Kevin J , Hoke Robert A , Kitano Masaru , Leslie Heather A , Lotufo Guilherme R , Parkerton Thomas F , Sappington Keith G , Tomy Gregg T , Woodburn Kent B
Published: April 2011

Standardized laboratory protocols for measuring the accumulation of chemicals from sediments are used in assessing new and existing chemicals, evaluating navigational dredging materials, and establishing site-specific biota–sediment accumulation factors (BSAFs) for contaminated sediment sites. The BSAFs resulting from the testing protocols provide insight into the behavior and risks associated with individual chemicals. In addition to laboratory measurement, BSAFs can also be calculated from field data, including samples from studies using in situ exposure chambers and caging studies. The objective of this report is to compare and evaluate paired laboratory and field measurement of BSAFs and to evaluate the extent of their agreement. The peer-reviewed literature was searched for studies that conducted laboratory and field measurements of chemical bioaccumulation using the same or taxonomically related organisms. In addition, numerous Superfund and contaminated sediment site study reports were examined for relevant data. A limited number of studies were identified with paired laboratory and field measurements of BSAFs. BSAF comparisons were made between field-collected oligochaetes and the laboratory test organism Lumbriculus variegatus and field-collected bivalves and the laboratory test organisms Macoma nasuta and Corbicula fluminea. Our analysis suggests that laboratory BSAFs for the oligochaete L. variegatus are typically within a factor of 2 of the BSAFs for field-collected oligochaetes. Bivalve study results also suggest that laboratory BSAFs can provide reasonable estimates of field BSAF values if certain precautions are taken, such as ensuring that steady-state values are compared and that extrapolation among bivalve species is conducted with caution. Integr Environ Assess Manag 2012;8:32–41. © 2011 SETAC
From Small Cucurbituril Complexes to Large Ordered Networks
Authors: Buschmann Hans‐Jürgen
Published: April 2011

Cucurbit[6]uril forms stable complexes with amine compounds in aqueous solutions. Some of the preformed complexes can be used for the synthesis of rotaxanes or polyrotaxanes. Polymers with threaded cucurbit[6]uril are also obtained from these complexes. Even by mixing a solid amino acid with solid cucurbit[6]uril a threading process takes place in the melt during the polycondensation. Structural flexible amino compounds are completely rigid after complex formation with cucurbit[6]uril. As a result, they are used as one component for the formation of polyelectrolyte layers on substrates. Furthermore some of the complexes, together with cations, are able to act as components in the formation of metal‐organic networks. Spectroscopic measurements indicate a well‐ordered formation of these networks.
Phthalate esters modulate the differentiation and maturation of mouse peripheral blood mononuclear cell‐derived dendritic cells
Authors: Ito Tomohiro , Inoue Ken‐ichiro , Nishimura Noriko , Takano Hirohisa
Published: April 2011

Phthalate esters, such as di‐(2‐ethylhexyl) phthalate (DEHP), are widespread environmental contaminants. Previously, we have observed that DEHP exacerbates dermatitis elicited by mite antigen in NC/Nga mice. Also, DEHP enhances the functions of bone marrow‐derived dendritic cells (DCs) in vitro. The present study sought to investigate whether phthalate esters affect peripheral blood mononuclear cell (PBMC)‐derived DCs of NC/Nga mice. First, we studied the time course of DC generation from PBMCs and the dose dependency of granulocyte macrophage colony‐stimulating factor and interleukin‐4, and then determined the conditions under which DC differentiation and maturation are moderately induced from PBMCs. Under the conditions determined above, DEHP at 10 μ m significantly inhibited the expression of DC differentiation and maturation markers, such as CD11c, CD40, CD80, CD86 and CD205, whereas mono‐(2‐ethylhexyl) phthalate, a metabolite of DEHP, did not. Furthermore, the effects of DEHP on PBMC‐derived DCs were partially rescued by treatment with ICI 182,780, an estrogen receptor antagonist. Taken together, these results suggest that DEHP can modulate the differentiation and maturation of mouse PBMC‐derived DCs at least partially through activation of the estrogen receptor under our experimental conditions.
Controlled and sustained gene delivery from injectable, porous PLGA scaffolds
Authors: Jeon Oju , Krebs Melissa , Alsberg Eben
Published: April 2011

Biodegradable poly(lactic‐co‐glycolic acid) (PLGA) scaffolds are widely used for the delivery of therapeutic molecules such as plasmid DNA (pDNA) and growth factors. However, many of these scaffolds must be implanted, and it would be beneficial to develop PGLA systems that can be injected in a minimally invasive manner. In this study, we present an injectable, porous PLGA scaffold that solidifies in situ for controlled gene delivery. Micro‐scale porosity was engineered into the system to facilitate cell migration, proliferation and extracellular matrix elaboration. Relatively rapid release of pDNA was achieved through simple mixing into the polymer solution prior to scaffold solidification, whereas sustained release was achieved by incorporating pDNA‐laden PLGA microspheres into the polymer solution. Sustained pDNA release was obtained for over 70 days. When the released pDNA was complexed with PEI and used to transfect HEK293 cells, substantial gene transfection was achieved from all time points, demonstrating that the pDNA was bioactive for the entire time course of the study. These in situ forming porous scaffolds for pDNA delivery are easy to prepare and can be injected without invasive surgery. Importantly, localized delivery of bioactive pDNA can be achieved for short to prolonged time periods, and small changes in the system composition permit facile tailoring of release profiles. In the future, this system may be used to control host cell regenerative responses by, for example, inducing cellular migration into the porous scaffold architecture via release of pDNA encoding for chemokines or pro‐angiogenic molecules. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
The sexual segment of hemidactylus turcicus and the evolution of sexual segment location in squamata
Authors: Rheubert Justin L. , Murray Christopher M. , Siegel Dustin S. , Babin Johnathan , Sever David M.
Published: April 2011

The kidneys of the Mediterranean Gecko, Hemidactylus turcicus (Gekkonidae), were investigated using light and electron microscopy with the primary focus placed on morphology of the sexual segment of the kidney. The nephrons of male H. turcicus are composed of five distinct regions: 1) a renal corpuscle and glomerulus, 2) a proximal convoluted tubule, 3) an intermediate segment, 4) a distal convoluted tubule, and 5) the sexual segment of the kidney/collecting duct. Female H. turcicus is similar but lack a sexual segment of the kidney. The sexual segment of the kidney is hypertrophied during the months of March through August, which corroborates previous reports of reproductive activity. During inactive months, the sexual segment of the kidney is nondiscernable from the collecting ducts. The sexual segment consists of tall columnar epithelial cells with basally positioned nuclei. Perinuclear Golgi complexes and rough endoplasmic reticulum are present. Secretory granules, which fill the apices of the epithelial cells, are electron dense and released into the lumen by a merocrine secretory process. Narrow intercellular canaliculi separate each epithelial cell and are sealed by tight junctions at the luminal aspect. Basally, leukoctyes are observed within the intercellular canaliculi and outside the basal lamina. Mast cells can be found just outside the basal lamina in close association with renal capillaries. The sexual segment of the kidney of H. turcicus is similar to that of three unrelated lizards for which ultrastructure was investigated with secretion mode being the major difference Also, H. turcicus is similar to most other lizards in that complete regression occurs during reproductive inactivity, but differs in this trait from the skink, Scincella lateralis, and most snakes which display a hypertrophied sexual segment of the kidney throughout the entire year. Although some unique similarities appear during the optimization, no direct patterns or directions are observed, and only the molecular based phylogeny resolves the ancestral condition of the Squamata as the sexual segment of the kidney being observed in the distal convoluted tubule, collecting duct, and ureter. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.
The gut of the juvenile African lungfish Protopterus annectens: A light and scanning electron microscope study
Authors: Icardo José M. , Wong Wai P. , Colvee Elvira , Garofalo Filippo , Loong Ai M. , Ip Yuen K.
Published: April 2011

We describe the microstructure of the alimentary canal of the juvenile lungfish Protopterus annectens. Following the oesophagus, the gut is formed by a long segment that extends down to the pyloric valve. This segment, classically named stomach, is lined by a transitional epithelium but lacks all characteristics of the vertebrate stomach. It has been defined here as the intestinal vestibule. The spiral valve is divided into a first large chamber, which contains mucosal ridges, and a second smooth portion. The entire spiral valve is lined with a pseudostratified columnar epithelium that contains approximately six cell types: enterocytes, goblet cells, ciliated cells, leukocytes, dark pigment cells, and vascular cells. Enterocytes and goblet cells show a high number of cytoplasmic vacuoles. The number and size of the vacuoles, and the number of ciliated cells, decreases from the anterior toward the posterior end, suggesting that most of the digestive processes take place in the anterior part of the spiral valve. The epithelium overlies a lamina propria in the first large chamber and a vascular plexus in the smooth portion. The cloaca has a thick muscular wall covered by a transitional epithelium. An extensive lymphatic system formed by capillaries and lymphatic micropumps is present along the entire wall of the alimentary canal. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.
Ultrastructure of the sexually dimorphic basitarsal glands of leg i in manaosbiid harvestmen (opiliones, laniatores)
Authors: Proud Daniel N. , Felgenhauer Bruce E.
Published: April 2011

Chemical communication is an important aspect of arthropod biology especially for those arthropods with limited abilities to detect visual and acoustic signals. Sexually dimorphic glands are often associated with the production of pheromones, which play a role in reproductive processes. In the family Manaosbiidae (Opiliones: Laniatores), males exhibit an enlarged, swollen, often fused, and spindle‐like basitarsus on leg I. In this study, we provide a novel description of the morphology and ultrastructure of the glandular structures found in the proximal swollen tarsomeres of the male manaosbiid Rhopalocranaus albilineatus Roewer, 1932 and compare the external leg I morphology with that of two other manaosbiid harvestmen (Barrona williamsi Goodnight and Goodnight, 1942 and Cranellus montgomeryi Goodnight and Goodnight, 1947). The two proximal tarsomeres of the male R. albilineatus leg I contain two large, paired, acinar glands consisting of many glandular cells. Cells empty their secretory products into a large, branched epicuticular duct, which exits the leg via a pore on the ventral region. Thus, a total of four glandular structures are present within the two swollen tarsomeres and each possesses a conducting canal and pore. Finally, we discuss possible roles of these basitarsal glands in manaosbiid reproductive biology based on the present understanding of sexually dimorphic glands in other terrestrial arthropods (i.e., insects and spiders). J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.
Testicular degeneration during spermatogenesis in the blue shark, Prionace glauca: Nonconformity with expression as seen in the diametric testes of other carcharhinids
Authors: McClusky Leon M.
Published: April 2011

The elasmobranch testis consists of spherical spermatocysts, each housing a single germ cell stage and its own clone of Sertoli cells. Because of the simple diametrical arrangement of cysts in maturational order, the testes of Squalus acanthias, Scyliorhinus canicula, and Prionace glauca are classified as the diametric shark testis type. The aim of this study was to document histologically the spermatocyst composition in the blue shark stage‐by‐stage and to establish whether the diametric testis type confers any uniformity regarding the expression of spermatogenesis in all sharks with this testis type. Analysis of the testes of blue sharks breeding in summer revealed extensive cyst degeneration of various forms and degrees, cyst shrinkage, and cyst disorganization with or without evidence of cell death, initially at the spermatogonia—spermatocyte transition but predominantly in spermatocyte and spermatid cysts. Animals could be grouped into two categories based on the major degenerative phenomena observed, namely those with extensive multinucleate cell (MNC) formation, and those with pronounced vacuolation in cysts. A major finding was the significant (P < 0.001) predominance of MNC formation and vacuolation in late‐stage spermatogonial cysts in the respective categories of sharks. Spermatocyte cysts showed varying degrees of germ cell depletion, with or without evidence of degeneration. Normal‐looking, but clearly subnormal‐sized primary and secondary spermatocyte cysts with no evidence of degeneration were significantly the dominant spermatocyte cyst types in both categories. It is proposed that these subnormal‐sized spermatocyte cysts could proceed into spermiogenesis. Because neighboring spermatid cysts lacked ordered bundling of spermatid heads (disorganized), a morphology significantly correlated with the vacuolation category of sharks, these results suggest that further progression into spermiogenesis was halted in such cysts. Thus, testicular degeneration in the diametric testis type is species specific in quantity and quality. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.
Differentiation of neural stem cells influences their chemotactic responses to vascular endothelial growth factor
Authors: Liu Jing , Wei Youhua , Chen Yebing , Xu Xiaojing , Zhang Huanxiang
Published: April 2011

Although much effort has been devoted to the delineation of factors involved in the migration of neural stem/progenitor cells (NSCs), the relationship between the chemotactic response and the differentiation status of these cells remains elusive. In the present study, we found that NSCs in varying differentiation states possess different chemotactic responses to vascular endothelial growth factor (VEGF): first, the number of chemotaxing NSCs and the optimal concentrations of VEGF that induced the peak migration vary greatly; second, time‐lapse video analysis shows that NSCs at certain differentiation states migrate more efficiently toward VEGF, although the migration speed remains unchanged irrespective of cell states; third, the phosphorylation status of Akt, ERK1/2, SAPK/JNK, and p38MAPK is closely related to the differentiation levels of NSCs subjected to VEGF; and, finally, although inhibition of ERK1/2 signaling significantly attenuates VEGF‐stimulated transfilter migration of both undifferentiated and differentiating NSCs, NSCs show normal chemotactic response after treatment with inhibitors of SAPK/JNK or p38MAPK. Meanwhile, interference with PI3K/Akt signaling prevents only NSCs of 12 hr differentiation, but not NSCs of 1 day or 3 days differentiation, from migrating in response to VEGF. Moreover, blocking of PI3K/Akt or MAPK signaling impairs the migration efficiency and/or speed, the extent of which depends on the cell differentiation status. Collectively, these results demonstrate that differentiation of NSCs influences their chemotactic responses to VEGF: NSCs in varying differentiation states have different migratory capacities, thereby shedding light on optimization of the therapeutic potential of NSCs to be employed for neural regeneration after injury. © 2011 Wiley‐Liss, Inc.
Activation and modulation of human α4β2 nicotinic acetylcholine receptors by the neonicotinoids clothianidin and imidacloprid
Authors: Li Ping , Ann Jason , Akk Gustav
Published: April 2011

Neonicotinoids are synthetic, nicotine‐derived insecticides used for agricultural and household pest control. Though highly effective at activating insect nicotinic receptors, many neonicotinoids are also capable of directly activating and/or modulating the activation of vertebrate nicotinic receptors. In this study, we have investigated the actions of the neonicotinoids clothianidin (CTD) and imidacloprid (IMI) on human neuronal α4β2 nicotinic acetylcholine receptors. The data demonstrate that the compounds are weak agonists of the human receptors with relative peak currents of 1–4% of the response to 1 mM acetylcholine (ACh). Coapplication of IMI strongly inhibited currents elicited by ACh. From Schild plot analysis, we estimate that the affinity of IMI for the human α4β2 receptor is 18 μM. The application of low concentrations of CTD potentiated responses to low concentrations of ACh, suggesting that receptors occupied by one ACh and one CTD molecule have a higher gating efficacy than receptors with one ACh bound. Interestingly, subunit stoichiometry affected inhibition by CTD, with (α4)2(β2)3 receptors significantly more strongly inhibited than the (α4)3(β2)2 receptors. © 2011 Wiley‐Liss, Inc.
Bone marrow mononuclear cells migrate to the demyelinated sciatic nerve and transdifferentiate into Schwann cells after nerve injury: Attempt at a peripheral nervous system intrinsic repair mechanism
Authors: Usach Vanina , Goitia Belén , Lavalle Lucía , Martinez Vivot Rocío , Setton‐Avruj Patricia
Published: April 2011

In the present work, we analyzed whether endogenous and/or transplanted bone marrow mononuclear cells (BMMC) migrate spontaneously to the crushed sciatic nerve and whether they transdifferentiate into Schwann cells (SC) in order to help repair the damaged tissue. We also studied both the immunohistochemical evolution of myelin proteins MBP and P0 and the myelin composition of both the proximal and distal stumps of the crushed sciatic nerve to determine the demyelination–remyelination period. Immunohistochemical analysis of crushed animals showed that the degeneration process consists of loss of nerve fiber integrity accompanied by degradation of myelin basic proteins MBP and P0, which is anticipated by protein cluster formation. The remyelination process appears as a recovery in nerve fiber structure as well as in MBP and P0 immunoreactivity; results obtained studying isolated myelin from the crushed sciatic nerve show a strong correlation between them. As opposed to demyelination, axonal damage is observed for a short period of time and takes place mostly in the crush area and the segments adjacent to the lesion. Evidence of spontaneous migration of endogenous or intravascularly transplanted BMMC (CD34+ and vimentin+) is found during the demyelination period exclusively to the injured sciatic nerve. Once migration takes place, transdifferentiation to SC is observed. Such migration and transdifferentiation processes might be inferred to constitute a spontaneous repair mechanism after nerve injury. © 2011 Wiley‐Liss, Inc.
Pectoralis major tendon rupture: A biomechanical analysis of repair techniques
Authors: Hart Nathan D. , Lindsey Derek P. , McAdams Timothy R.
Published: April 2011

Rupture of the insertion of the pectoralis major muscle to the proximal humerus is becoming a common injury. Repair of these ruptures increases patient satisfaction, strength, and cosmesis, and shortens return to competitive sports. Several repair techniques have been described, but recently many surgeons are using suture anchors. The traditional repair technique uses transosseous sutures, but no study has biomechanically compared the strength of these two repair techniques in human cadavers. Twelve fresh‐frozen human shoulder specimens were dissected. The pectoralis major tendon insertion was cut from the bone and repaired using one of the two repair techniques: specimens were randomly assigned to transosseous trough with suture tied over bone versus four suture anchors. The fixation constructs were pulled to failure at 4 mm/s on a materials testing system. The mean ultimate failure load of the transosseous repairs was 611 N and the mean ultimate failure load of the suture anchor repair was 620 N. The mean stiffness of the transosseous repair was 32 and 28 N/mm for the suture anchor group. We found no statistically significant difference between these two repair techniques. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1783–1787, 2011
Are polymorphisms of molecules involved in bone healing correlated to aseptic femoral and tibial shaft non‐unions?
Authors: Zeckey Christian , Hildebrand Frank , Glaubitz Lena‐Marie , Jürgens Simon , Ludwig Theresa , Andruszkow Hagen , Hüfner Tobias , Krettek Christian , Stuhrmann Manfred
Published: April 2011

Fracture healing is a well‐organized process between several molecules and mediators. As known from other diseases, genetic polymorphisms may exhibit different expression patterns in these mediators. Concerning fracture healing, this may lead to an extended healing process or non‐union. We investigated the incidence of polymorphisms in patients with aseptic non‐unions after femoral and tibial shaft fractures as compared to patients with uneventful healing. Exclusion criteria were smoking, diabetes, bilateral fractures, systemic corticoid therapy, and septic non‐unions. Analysis of allele frequencies and genotype distribution of various mediators were carried out following PCR. Clinical parameters such as injury severity and in‐hospital were analyzed. Fifty patients following non‐union (group NU) were enrolled, the control group consisted of 44 patients (group H). A significant association of a PDGF haplotype and non‐unions following fracture could be observed. There was a significantly increased in‐hospital time and amount of surgical procedures in group NU. Polymorphisms within the PDGF gene seem to be a genetic risk factor for the development of non‐unions of the lower extremity following fracture. The early identification of high risk patients could result in an adapted therapeutical strategy and might contribute to a significant decrease of posttraumatic non‐unions. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1724–1731, 2011
Short‐term test–retest reproducibility of urethral pressure profilometry in women with urodynamic stress incontinence with and without detrusor overactivity
Authors: Rahmanou Philip , Khullar Vik
Published: April 2011

Aims

To determine and compare reproducibility of urethral pressure profilometry (UPP) in women with urodynamic stress incontinence (USI) alone or together with detrusor overactivity (DO).

Methods

Women were recruited from a urodynamic clinic diagnosed with USI using dual channel cystometry. UPP was performed with the technique described by Hilton and Stanton [Hilton P, Stanton SL. Br J Obstet Gynaecol 90:919–33,1983]. Different urethral function parameters were obtained. Two weeks later the tests were repeated. The precision and bias of the tests were measured using the Bland and Altman method [Bland JM, Altman DG. Lancet 1:307–10,1986]. The coefficient of variation (CV) value allowed direct comparison of repeatability of each test, with a lower value indicating less variation.

Results

Thirty‐one women completed both visits. Fourteen women had USI, the other 17 diagnosed with USI with DO at the end of two visits. There was no significant difference between visits for all the parameters for all women recruited. The most reproducible parameter was functional urethral length and maximum urethral pressure as demonstrated by lowest CV.

The women with USI group had more reproducible UPP parameters than those with mixed USI and DO in all parameters apart from pressure transmission ratio in Quartiles 2, 3, and 4. However, there was no significant difference between the two diagnostic groups.

Conclusions

Tests of urethral function in urethral pressure profilometry are shown to have poor reproducibility in women with USI, but limit of agreement may be acceptable in some of the tests. The with‐in subject CV appears to be higher in women with mixed USI and DO compared to USI only. Neurourol. Urodynam. 30:1356–1360, 2011. © 2010 Wiley‐Liss, Inc.
Predictor of de novo urinary incontinence following holmium laser enucleation of the prostate
Authors: Cho Min Chul , Park Ji Hyun , Jeong Min Su , Yi Jun‐Seok , Ku Ja Hyeon , Oh Seung‐June , Kim Soo Woong , Paick Jae‐Seung
Published: April 2011

Aims

To investigate the incidence of de novo urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia and to determine predictors of postoperative de novo UI.

Methods

A total of 204 men who underwent HoLEP and in whom 12‐month follow‐up data on UI were available were included in this study. The efficacy of HoLEP was assessed at 1‐, 3‐, 6‐, and 12‐month postoperatively using the International Prostate Symptom Score (IPSS) and with uroflowmetry. The presence or absence of UI was recorded at each follow‐up visit. All definitions of UI corresponded to recommendations of the International Continence Society.

Results

The mean preoperative total prostate and transition zone volumes were 53.3 (range 20–162) g and 27.2 (range 4–107) g, respectively. The mean enucleated weight was 23.0 (range 3.0–82.3) g. The IPSS and uroflowmetry showed that all micturition parameters improved significantly starting at 1‐month postoperatively. After HoLEP, 29 patients (16.2%) had de novo UI, most of which resolved within 1–6 months; 11 had stress UI, 12 had urgency UI, and the remaining 6 had mixed UI. On logistic regression analysis, bladder mucosal injury during morcellation and maximum urethral closure pressure on baseline urodynamics were the independent predictors of de novo UI after surgery.

Conclusions

Our data suggest that HoLEP is effective in improving micturition, but de novo postoperative UI occurred in some patients although usually transient. Surgeons should be careful to not injure the bladder mucosa during morcellation. Neurourol. Urodynam. 30:1343–1349, 2011. © 2011 Wiley‐Liss, Inc.
Assessment of therapeutic response and treatment planning for brain tumors using metabolic and physiological MRI
Authors: Nelson Sarah J.
Published: April 2011

MRI is routinely used for diagnosis, treatment planning and assessment of response to therapy for patients with glioma. Gliomas are spatially heterogeneous and infiltrative lesions that are quite variable in terms of their response to therapy. Patients classified as having low‐grade histology have a median overall survival of 7 years or more, but need to be monitored carefully to make sure that their tumor does not upgrade to a more malignant phenotype. Patients with the most aggressive grade IV histology have a median overall survival of 12–15 months and often undergo multiple surgeries and adjuvant therapies in an attempt to control their disease. Despite improvements in the spatial resolution and sensitivity of anatomic images, there remain considerable ambiguities in the interpretation of changes in the size of the gadolinium‐enhancing lesion on T1‐weighted images as a measure of treatment response, and in differentiating between treatment effects and infiltrating tumor within the larger T2 lesion. The planning of focal therapies, such as surgery, radiation and targeted drug delivery, as well as a more reliable assessment of the response to therapy, would benefit considerably from the integration of metabolic and physiological imaging techniques into routine clinical MR examinations. Advanced methods that have been shown to provide valuable data for patients with glioma are diffusion, perfusion and spectroscopic imaging. Multiparametric examinations that include the acquisition of such data are able to assess tumor cellularity, hypoxia, disruption of normal tissue architecture, changes in vascular density and vessel permeability, in addition to the standard measures of changes in the volume of enhancing and nonenhancing anatomic lesions. This is particularly critical for the interpretation of the results of Phase I and Phase II clinical trials of novel therapies, which are increasingly including agents that are designed to have anti‐angiogenic and anti‐proliferative properties as opposed to having a direct effect on tumor cell viability. Copyright © 2011 John Wiley & Sons, Ltd.
Ursodeoxycholic acid treatment of hepatic steatosis: a 13C NMR metabolic study
Authors: Nunes Patrícia M. , Jones John G. , Rolo Anabela P. , Palmeira Carlos M. M. , Carvalho Rui A.
Published: April 2011

Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disorders. In this study, we tested whether a 4‐week treatment with this bile acid (12–15 mg/kg/day) could improve hepatic fatty acid oxidation in obese Zucker rats – a model for nonalcoholic fatty liver disease and steatosis. After 24 h of fasting, livers were perfused with physiological concentrations of [U‐13C]nonesterified fatty acids and [3‐13C]lactate/[3‐13C]pyruvate. Steatosis was associated with abundant intracellular glucose, lactate, alanine and methionine, and low concentrations of choline and betaine. Steatotic livers also showed the highest output of glucose and lactate. Glucose and glycolytic products were mostly unlabeled, indicating active glycogenolysis and glycolysis after 24 h of fasting. UDCA treatment resulted in a general amelioration of liver metabolic abnormalities with a decrease in intracellular glucose and lactate, as well as their output. Hepatic betaine and methionine were also normalized after UDCA treatment, suggesting the amelioration of anti‐oxidative defenses. Choline levels were not affected by the bile acid, which may indicate a deficient synthesis of very‐low‐density lipoproteins. The percentage contribution of [U‐13C]nonesterified fatty acids to acetyl‐coenzyme A entering the tricarboxylic acid (TCA) cycle was significantly lower in livers from Zucker obese rats relative to control rats: 23.1 ± 4.9% versus 44.1 ± 2.7% (p < 0.01). UDCA treatment did not alter significantly fatty acid oxidation in control rats, but improved significantly oxidation in Zucker obese rats to 46.0 ± 6.1% (p > 0.05), comparable with control group values. The TCA cycle activity subsequent to fatty acid oxidation was reduced in steatotic livers and improved when UDCA was administered (0.24 ± 0.04 versus 0.37 ± 0.05, p = 0.05). We further suggest that the mechanism of action of UDCA is either related to the activity of the farnesoid receptor, or to the amelioration of the anti‐oxidative defenses and cell nicotinamide adenine dinucleotide (NAD+/NADH) ratio, favoring TCA cycle activity and β‐oxidation. Copyright © 2011 John Wiley & Sons, Ltd.
Using spatial prior knowledge in the spectral fitting of MRS images
Authors: Kelm B. Michael , Kaster Frederik O. , Henning Anke , Weber Marc‐André , Bachert Peter , Boesiger Peter , Hamprecht Fred A. , Menze Bjoern H.
Published: April 2011

We propose a Bayesian smoothness prior in the spectral fitting of MRS images which can be used in addition to commonly employed prior knowledge. By combining a frequency‐domain model for the free induction decay with a Gaussian Markov random field prior, a new optimization objective is derived that encourages smooth parameter maps. Using a particular parameterization of the prior, smooth damping, frequency and phase maps can be obtained whilst preserving sharp spatial features in the amplitude map. A Monte Carlo study based on two sets of simulated data demonstrates that the variance of the estimated parameter maps can be reduced considerably, even below the Cramér–Rao lower bound, when using spatial prior knowledge. Long‐TE 1H MRSI at 1.5 T of a patient with a brain tumor shows that the use of the spatial prior resolves the overlapping peaks of choline and creatine when a single voxel method fails to do so. Improved and detailed metabolic maps can be derived from high‐spatial‐resolution, short‐TE 1H MRSI at 3 T. Finally, the evaluation of four series of long‐TE brain MRSI data with various signal‐to‐noise ratios shows the general benefit of the proposed approach. Copyright © 2011 John Wiley & Sons, Ltd.
Topology optimization of planar shape memory alloy thermal actuators using element connectivity parameterization
Authors: Langelaar M. , Yoon G. H. , Kim Y. Y. , van Keulen F.
Published: April 2011

This paper presents the direct application of topology optimization to the design of shape memory alloy (SMA) thermal actuators. Because SMAs exhibit strongly nonlinear, temperature‐dependent material behavior, designing effective multidimensional SMA actuator structures is a challenging task. We pursue the use of topology optimization to address this problem. Conventional material scaling topology optimization approaches are hampered by the complexity of the SMA constitutive behavior combined with large actuator deflections. Therefore, for topology optimization we employ the element connectivity parameterization approach, which offers improved analysis convergence and robustness, as well as an unambiguous treatment of nonlinear materials. A path‐independent SMA constitutive model, aimed particularly at the NiTi R‐phase transformation, is employed, allowing efficient adjoint sensitivity analysis. The effectiveness of the proposed SMA topology optimization is demonstrated by numerical examples of constrained and unconstrained formulations of actuator stroke maximization, which provide insight into the characteristics of optimal SMA actuators. Copyright © 2011 John Wiley & Sons, Ltd.
Deflated preconditioned conjugate gradient solvers for linear elasticity
Authors: Aubry R. , Mut F. , Dey S. , Löhner R.
Published: April 2011

Extensions of deflation techniques previously developed for the Poisson equation to static elasticity are presented. Compared to the (scalar) Poisson equation (J. Comput. Phys. 2008; 227(24):10196–10208; Int. J. Numer. Meth. Engng 2010; DOI: 10.1002/nme.2932; Int. J. Numer. Meth. Biomed. Engng 2010; 26(1):73–85), the elasticity equations represent a system of equations, giving rise to more complex low‐frequency modes (Multigrid. Elsevier: Amsterdam, 2000). In particular, the straightforward extension from the scalar case does not provide generally satisfactory convergence. However, a simple modification allows to recover the remarkable acceleration in convergence and CPU time reached in the scalar case. Numerous examples and timings are provided in a serial and a parallel context and show the dramatic improvements of up to two orders of magnitude in CPU time for grids with moderate graph depths compared to the non‐deflated version. Furthermore, a monotonic decrease of iterations with increasing subdomains, as well as a remarkable acceleration for very few subdomains are also observed if all the rigid body modes are included. Copyright © 2011 John Wiley & Sons, Ltd.