bluuebunny/crossref_metadata_2025 huggingface dataset:
In utero transplanted human hepatocytes allow postnatal engraftment of human hepatocytes in pigs
Authors: Fisher James E. , Lillegard Joseph B. , Mckenzie Travis J. , Rodysill Brian R. , Wettstein Peter J. , Nyberg Scott L.
Published: December 2012

In utero cell transplantation (IUCT) can lead to the postnatal engraftment of human cells in the xenogeneic recipient. Most reports of IUCT have involved hematopoietic stem cells. It is unknown whether human hepatocytes used for IUCT in fetal pigs will lead to the engraftment of these same cells in the postnatal environment. In this study, fetal pigs received direct liver injections of 1 × 107 human hepatocytes in utero and were delivered by cesarean section at term. The piglets received a second direct liver injection of 5 × 107 human hepatocytes 1 week after birth. The serum was analyzed for human albumin 2, 4, and 6 weeks after engraftment. Piglet livers were harvested 6 weeks after transplantation and were examined by immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization for human-specific sequences. Piglets undergoing IUCT with human hepatocytes that were postnatally engrafted with human hepatocytes showed significant levels of human albumin production in their serum at all postengraftment time points. Human albumin gene expression, the presence of human hepatocytes, and the presence of human beta-2 microglobulin were all confirmed 6 weeks after engraftment. IUCT in fetal pigs with human hepatocytes early in gestation allowed the engraftment of human hepatocytes, which remained viable and functional for weeks after transplantation. IUCT followed by postnatal engraftment may provide a future means for large-scale expansion of human hepatocytes in genetically engineered pigs.
Ancestral founder mutations in calpain‐3 in the Indian Agarwal community: Historical, clinical, and molecular perspective
Authors: Ankala Arunkanth , Kohn Jordan N. , Dastur Rashna , Gaitonde Pradnya , Khadilkar Satish V. , Hegde Madhuri R.
Published: December 2012

Introduction

Clinical heterogeneity of limb‐girdle muscular dystrophies (LGMDs, 24 known subtypes), which includes overlapping phenotypes and varying ages of onset and morbidity, adds complexity to clinical and molecular diagnoses.

Methods

To diagnose LGMD subtype, protein analysis, using immunohistochemistry (IHC) and immunoblotting, was followed by gene sequencing through a panel approach (simultaneous sequencing of known LGMD genes) in 9 patients from unrelated families of the Indian Agarwal community. Haplotype studies were performed by targeted SNP genotyping to establish mutation segregation.

Results

We identified 2 founder mutations in CAPN3, a missense (c.2338G>C; p.D780H) and a splice‐site (c.2099‐1G>T) mutation, on 2 different haplotype backgrounds. The patients were either heterozygous for both or homozygous for either of these mutations.

Conclusions

Founder mutations have immediate clinical application, at least in selected population groups. Clinically available gene panels may provide a definitive molecular diagnosis for heterogeneous disorders such as LGMD. Muscle Nerve 47: 931–937, 2013
The influence of diffusion time on the properties of sequential interpenetrating PEG hydrogels
Authors: Yang Ting , Malkoch Michael , Hult Anders
Published: December 2012

Four sets comprising a total of 16 sequential interpenetrating network (SeqIPN) hydrogels were efficiently fabricated via UV initiated thiol‐ene coupling chemistry and from 2 kDa or 8 kDa primary poly(ethylene glycol) (PEG) networks (S2 and S8). Each primary system delivered four different SeqIPNs constructed after 2, 4, 20, and 44 h diffusion of secondary network PEG precursors, 2 kDa and 8 kDa. This allowed the assessment of both mechanical and swelling properties for a wide range of novel hydrogels ranging from loosely crosslinked SeqIPN 8‐8 to densely crosslinked SeqIPN 2‐2 systems. All gel fractions of secondary networks were above 83% and 44 h of diffusion was found sufficient to fully saturate the primary networks. Disperse red functionalized PEGs (2 kDa and 8 kDa) were further used as probes to investigate the diffusion mechanisms. The impact of diffusion time on loosely crosslinked S8 network with a swelling degree of 970% and tensile modulus of 175 kPa displayed a significant change in the final properties. For instance, a 2 h diffusion of 2 kDa PEG precursors generated a SeqIPN 8‐2:2 comprising a secondary network solid content of 34% with a water swelling degree 580% and a tensile modulus of 365 kPa. On saturation, that is, 44 h of diffusion, SeqIPN 2‐8:44 exhibited 64% of secondary network solid content, a swelling capacity of 380% and over fourfold of tensile modulus (758 kPa) when compared with the primary network S8. SeqIPN hydrogel with the highest tensile modulus and lowest degree of water swelling was obtained after 44 h diffusion of 2 kDa PEG precursors within the densely crosslinked S2 primary network. In this case, SeqIPN 2‐2:44 noted a water swelling capability of 280% and a tensile modulus over 1 MPa. The latter was twofold when compared with S2 with a tensile modulus of 555 kPa. Consequently, the diffusion time of secondary network is a promising parameter to control and that enables the fabrication of PEG hydrogels with a wider window of mechanical and swelling properties. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
A non‐phosgene process to homopolycarbonate and copolycarbonates of isosorbide using dimethyl carbonate: Synthesis, characterization, and properties
Authors: Li Qian , Zhu Wenxiang , Li Chuncheng , Guan Guohu , Zhang Dong , Xiao Yaonan , Zheng Liuchun
Published: December 2012

Poly(isosorbide carbonate) (PIC) was synthesized by melt polycondensation of dimethyl carbonate (DMC) and isosorbide using lithium acetylacetonate (LiAcac) as the catalyst. The reaction conditions were optimized to achieve PIC with relatively high number‐average molecular weight (Mn) of 28,800 g/mol and isosorbide conversion of 95.2%. A series of poly(aliphatic diol‐co‐isosorbide carbonate)s (PAICs) were also synthesized by melt polycondensation of DMC with isosorbide and equimolar amounts of aliphatic diols (1,4‐butanediol, 1,5‐pentanediol, 1,6‐hexanediol, and 1,4‐cyclohexane dimethanol) in the presence of LiAcac and the TiO2/SiO2‐based catalyst (TSP‐44). PAICs with Mn values ranging from 18,700 to 34,400 g/mol and polydispersities between 1.64 and 1.69 were obtained. The 13C NMR analysis revealed the random microstructure of PAICs. The differential scanning calorimetry results demonstrated that all the PAICs were amorphous with a unique Tg ranging from 46 to 88 °C. The dynamic analysis results showed that the incorporation of linear or cyclohexane structure changed the dynamic mechanical properties of PIC drastically. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Synthesis and radical polymerization of styrene‐based monomer having a five‐membered cyclic dithiocarbonate structure
Authors: Miyata Takahiro , Matsumoto Kozo , Endo Takeshi , Yonemori Shigeaki , Watanabe Shoji
Published: December 2012

A styrene‐based monomer having a five‐membered cyclic dithiocarbonate structure, 4‐vinylbenzyl 1,3‐oxathiolane‐2‐thione‐5‐ylmethyl ether (VBTE), was synthesized from 4‐vinylbenzyl glycidyl ether (VBGE) and carbon disulfide in the presence of lithium bromide in 86% yield. Radical polymerization of VBTE in dimethyl sulfoxide by 2,2′‐azobisisobutyronitrile was carried out at 60 °C to afford the corresponding the polymer, polyVBTE, in 64% yield. PolyVBTE with number‐averaged molecular weight higher than 31,000 was obtained. The glass transition temperature (Tg) and 5 wt % decomposition temperature (Td5) of the polyVBTE were evaluated to be 66 and 264 °C under nitrogen atmosphere by differential scanning calorimetry and thermal gravimetry analysis, respectively. It was confirmed that a polymer consisting of the same VBTE repeating unit could also be obtained via polymer reaction, that is, a lithium bromide‐catalyzed addition of carbon disulfide to a polyVBGE prepared from a radical polymerization of VBGE. Copolymerization of VBTE and styrene with various compositions efficiently gave copolymers of VBTE and styrene. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
New tethered ansa‐bridged zirconium catalysts: Insights into the “self‐immobilization” mechanism
Authors: Polo Eleonora , Losio Simona , Sacchi Maria Carmela , Galimberti Maurizio
Published: December 2012

New ω‐alkenyl‐substituted ansa‐bridged bisindenyl zirconium complexes are prepared and tested as self‐immobilized catalysts for ethene polymerization. But, even at very high concentration of the tethered complexes and low pressure of ethene, there is no evidence of their insertion into the polyethene chain. A “cross polymerization” test, performed by copolymerizing the tethered complexes with ethene using rac‐Me2Si(2‐MeBenzInd)2ZrCl2 (MBI), does not lead to their incorporation into the polyethene chain. However, the corresponding ligand proves to be a suitable comonomer for ethene, and, through copolymerization promoted by MBI, innovative poly(ethene‐co‐2,2′‐bis[(1H‐inden‐3′‐yl)‐hex‐5‐ene) copolymers are prepared and characterized by 13C NMR. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
Electrospinning of biostable polyisobutylene‐based thermoplastic polyurethanes
Authors: Cozzens David , Wei Xinyu , Faust Rudolf
Published: December 2012

Electrospinning of a previously synthesized biostable polyisobutylene (PIB)‐based thermoplastic polyurethanes (TPU) have been performed as materials with potential applications as vascular grafts. Electrospun mats were generated with fiber diameters in the submicron to 2 μm range as observed using scanning electron microscopy. Porosity of electrospun TPU fiber mats was investigated using Hg intrusion porosimetry. Fiber mats were found to have a distribution of pore sizes between 100 nm and 100 μm, with overall porosity between 50 and 70%. Thermal analysis of electrospun mats showed orientation of the TPU chains compared to the bulk as‐synthesized material. Tensile failure properties were characterized, showing ultimate tensile strength of 1.6–6.5 MPa and ultimate elongation of ∼300–100% with TPUs of increasing hardness from Shore 60A to 100A. Strain‐recovery experiments showed good recovery of tensile strain at significant stresses. The previously demonstrated biostability of these PIB‐based TPUs, together with the excellent reported mechanical properties, indicates great promise for these materials as biostable vascular grafts. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Binary Flash Compositions – A Theoretical and Practical Study
Authors: Klapötke Thomas M. , Steemann F. Xaver , Suceska Muhammad
Published: December 2012

Flash compositions are a class of pyrotechnic effect compositions used in firecrackers as well as in military applications. They are widely recognized as perhaps the most dangerous pyrotechnic compositions. This study investigates binary flash compositions containing aluminum and (per)chlorate oxidizers. The sensitivities of binary flash compositions are measured, their explosive power is compared using micro‐scale ballistic mortar testing, and their detonation parameters are calculated using the EXPLO5 code.
Cycle‐walking revisited: consistency, security, and efficiency
Authors: Li Jingwei , Jia Chunfu , Liu Zheli , Dong Zongqing
Published: December 2012

Cycle‐walking is a method that makes sure ciphertext falls in the acceptable range through encrypting plaintext repeatedly with some underlying cipher. This technology provides a general way to construct cryptographic schemes for various interesting applications, including enhancing existing system security without the change of original structure, encrypting multimedia data with the preservation of scalability, generating credit card numbers for Web transaction, and so on, which have a common feature that ciphertext is required to satisfy certain restrictions in order to allow some operations directly imposed on encrypted data. Nevertheless, as far as we know, there exists little work making rigorous analysis on cycle‐walking, especially its undeterministic efficiency, which may limit the application of schemes constructed by such technology or even lead it to unpracticality. In this paper, aiming at filling some gaps about cycle‐walking and helping cryptographic theory “catch up” with its application, we present the rigorous analysis on cycle‐walking's properties including consistency, security, and efficiency. On consistency, we show that cycle‐walking will necessarily arrive back with finite iteration rounds and its decryption reverses encryption. On security, we show that cycle‐walking would not degrade the security of underlying ciphers. On efficiency, instead of using “nondeterministic” to describe cycle‐walking's performance in previous work, we make precise analysis and provide the answer to “how long is the duration of cycle‐walking's encrypting process.” Copyright © 2012 John Wiley & Sons, Ltd.
Umbilical Cord Blood Therapy Potentiated with Erythropoietin for Children with Cerebral Palsy: A Double-blind, Randomized, Placebo-Controlled Trial
Authors: Min Kyunghoon , Song Junyoung , Kang Jin Young , Ko Jooyeon , Ryu Ju Seok , Kang Myung Seo , Jang Su Jin , Kim Sang Heum , Oh Doyeun , Kim Moon Kyu , Kim Sung Soo , Kim MinYoung
Published: December 2012

Allogeneic umbilical cord blood (UCB) has therapeutic potential for cerebral palsy (CP). Concomitant administration of recombinant human erythropoietin (rhEPO) may boost the efficacy of UCB, as it has neurotrophic effects. The objectives of this study were to assess the safety and efficacy of allogeneic UCB potentiated with rhEPO in children with CP. Children with CP were randomly assigned to one of three parallel groups: the pUCB group, which received allogeneic UCB potentiated with rhEPO; the EPO group, which received rhEPO and placebo UCB; and the Control group, which received placebo UCB and placebo rhEPO. All participants received rehabilitation therapy. The main outcomes were changes in scores on the following measures during the 6 months treatment period: the gross motor performance measure (GMPM), gross motor function measure, and Bayley scales of infant development-II (BSID-II) Mental and Motor scales (18). F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET/CT) and diffusion tensor images (DTI) were acquired at baseline and followed up to detect changes in the brain. In total, 96 subjects completed the study. Compared with the EPO (n = 33) and Control (n = 32) groups, the pUCB (n = 31) group had significantly higher scores on the GMPM and BSID-II Mental and Motor scales at 6 months. DTI revealed significant correlations between the GMPM increment and changes in fractional anisotropy in the pUCB group. 18F-FDG-PET/CT showed differential activation and deactivation patterns between the three groups. The incidence of serious adverse events did not differ between groups. In conclusion, UCB treatment ameliorated motor and cognitive dysfunction in children with CP undergoing active rehabilitation, accompanied by structural and metabolic changes in the brain.
What are the Main Running-Related Musculoskeletal Injuries?
Authors: Lopes Alexandre Dias , Hespanhol Luiz Carlos , Yeung Simon S. , Costa Leonardo Oliveira Pena
Published: December 2012

Background

Musculoskeletal injuries occur frequently in runners and despite many studies about running injuries conducted over the past decades it is not clear in the literature what are the main running-related musculoskeletal injuries (RRMIs).

Objective

The aim of this study is to systematically review studies on the incidence and prevalence of the main specific RRMIs.

Methods

An electronic database search was conducted using EMBASE (1947 to October 2011), MEDLINE (1966 to October 2011), SPORTDiscus™ (1975 to October 2011), the Latin American and Caribbean Center on Health Sciences Information (LILACS) [1982 to October 2011] and the Scientific Electronic Library Online (SciELO) [1998 to October 2011] with no limits of date or language of publication. Articles that described the incidence or prevalence rates of RRMIs were considered eligible. Studies that reported only the type of injury, anatomical region or incomplete data that precluded interpretation of the incidence or prevalence rates of RRMIs were excluded. We extracted data regarding bibliometric characteristics, study design, description of the population of runners, RRMI definition, how the data of RRMIs were collected and the name of each RRMI with their rates of incidence or prevalence. Separate analysis for ultra-marathoners was performed. Among 2924 potentially eligible titles, eight studies (pooled n = 3500 runners) were considered eligible for the review. In general, the articles had moderate risk of bias and only one fulfilled less than half of the quality criteria established.

Results

A total of 28 RRMIs were found and the main general RRMIs were medial tibial stress syndrome (incidence ranging from 13.6% to 20.0%; prevalence of 9.5%), Achilles tendinopathy (incidence ranging from 9.1% to 10.9%; prevalence ranging from 6.2% to 9.5%) and plantar fasciitis (incidence ranging from 4.5% to 10.0%; prevalence ranging from 5.2% to 17.5%). The main ultra-marathon RRMIs were Achilles tendinopathy (prevalence ranging from 2.0% to 18.5%) and patellofemoral syndrome (prevalence ranging from 7.4% to 15.6%).

Conclusion

This systematic review provides evidence that medial tibia stress syndrome, Achilles tendinopathy and plantar fasciitis were the main general RRMIs, while Achilles tendinopathy and patellofemoral syndrome were the most common RRMIs for runners who participated in ultra-marathon races.
Walter’s two-layer hypothesis revisited: back to the roots!
Authors: Ward David , Wiegand Kerstin , Getzin Stephan
Published: December 2012

Walter (Jahrb Wiss Bot 87:750–860, 1939) proposed a two-layer hypothesis, an equilibrium explanation for coexistence of savanna trees and grasses. This hypothesis relies on vertical niche partitioning and assumed that grasses are more water-use efficient than trees and use subsurface water while trees also have access to deeper water sources. Thus, in open savannas, grasses were predicted to predominate because of their water use efficiency and access to subsurface water. This hypothesis has been a prominent part of the savanna literature since first proposed. We review the literature on Walter’s hypothesis and reconsider his original intentions. Walter intended this hypothesis to be restricted to dry savannas. In his opinion, mesic and humid savannas were controlled by biotic factors and disturbances. We surveyed the global savanna literature for records of vertical niche partitioning by grasses and trees. We find that, within the scope of Walter’s original intentions, this hypothesis works remarkably well, and in some cases is appropriate for deserts as well as for dry temperate systems and even some mesic savannas.
Salt Effect on Mixed Micelle and Interfacial Properties of Conventional Cationic Surfactants and the Ionic Liquid Surfactant 1‐Tetradecyl‐3‐methylimidazolium Bromide ([C14mim]Br)
Authors: Luo Genxiang , Qi Xinjie , Han Chunyu , Liu Chunsheng , Gui Jianzhou
Published: December 2012

The surface properties and mixed micellization behavior of binary combinations of an ionic liquid surfactant, namely, 1‐tetradecyl‐3‐methylimidazolium bromide ([C14mim]Br) with common cationic surfactants viz. tetradecyltrimethylammonium bromide and tetradecylpyridinium bromide in the presence of sodium bromide (NaBr) were investigated by surface tension and conductivity measurements. The critical micelle concentration (CMC) and interfacial parameters, such as the maximum surface excess (Γmax), minimum area per molecule (Amin) and surface pressure at the CMC (πCMC) were determined from the surface tension data. The CMC and Γmax values were found to decrease with increasing salt concentrations. The and values are negative indicating the spontaneity of micelle formation.
Tetradecylthioacetic Acid Increases Fat Metabolism and Improves Cardiac Function in Experimental Heart Failure
Authors: Øie Erik , Berge Rolf K. , Ueland Thor , Dahl Christen P. , Edvardsen Thor , Beitnes Jan Otto , Bohov Pavol , Aukrust Pål , Yndestad Arne
Published: December 2012

Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β‐oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high‐fat or regular diet, in a rat model of post‐myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post‐myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n‐3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n‐6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n‐3 PUFA could reflect increased n‐3 PUFA synthesis and inadequately increased n‐3 PUFA β‐oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n‐3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n‐3 PUFA.
Rapid Assessment of Quality Parameters in Cocoa Butter Using ATR‐MIR Spectroscopy and Multivariate Analysis
Authors: Maurer Natalie E. , Rodriguez‐Saona Luis
Published: December 2012

The development of sensitive and robust screening tool(s) for assuring the quality of incoming raw materials would supplement the assurances provided by food manufacturer vendor auditing programs. Our aim was to evaluate the ability of attenuated total reflectance mid‐infrared (ATR‐MIR) spectroscopy in combination with multivariate analysis as a screening tool for the diverse cocoa butter supply. Forty different cocoa butter samples encompassing an acceptable range of compositional variability for the chocolate industry were included. Cocoa butters were characterized for their melt characteristics (melting heat), triacylglycerol content and fatty acid composition (GC‐FAME). Soft independent modeling of class analogy (SIMCA) and partial least squares regression (PLSR) were used for classification and quantification analysis. SIMCA classified all cocoa butters in distinct clusters in a 3‐dimensional space but no sample clustering patterns were associated with melt characteristics. Spectral differences responsible for the separation of classes were attributed to stretching vibrations of the ester (–C=O) linkage (1,660–1,720 cm−1). PLSR models showed correlation coefficients >0.93 and prediction errors (SECV) of 1.5 units for melt characteristics, 0.2–0.3 and 0.4–0.8 % for major fatty acids and triacylglycerols, respectively. ATR‐MIR spectroscopy combined with pattern recognition analysis provides robust models for characterization and determination of cocoa butter composition.
Chemical Stability of the Lipid Phase in Concentrated Beverage Emulsions Colored with Natural β‐Carotene
Authors: Szterk Arkadiusz , Roszko Marek , Górnicka Ewa
Published: December 2012

The aim of this study was to examine the oxidation of selected plant oils in concentrated beverage emulsions colored with natural β‐carotene. Carotenoid preparations obtained from carrots were dissolved in cold‐pressed linseed oil, refined canola oil, and refined palm olein. Oxidative stability of the lipids was examined with and without addition of the pigment to the oil/water (O/W) emulsion. Carotenoid/lipid hydro peroxide (LOOH) concentration was evaluated using two different methods: LOOH + Fe2+ reaction connected with a colored complex of ammonium thiocyanate determined with the help of a spectrophotometer, and LOOH determined with the help of a chemiluminometer. It was shown that oxidation rate of lipids in the O/W emulsions strongly depended on chemical composition of the lipid fraction (type of oil used). Presence of the carotenoid pigment increased the rate. Therefore, if a carotenoid‐containing emulsion is to be stable, it should be based on oils of a high oxidative stability.
Posterior instrumentation and fusion
Authors: Deniz Olgun Z. , Yazici Muharrem
Published: December 2012

The purpose of surgery for adolescent idiopathic scoliosis, which characteristically includes thoracic hypokyphosis and all three columns of the spine, is the achievement of a balanced spine while preserving as many motion segments as possible and avoiding neurologic damage. Many approaches have been defined in the treatment of this common disease. Posterior-only surgery, instrumentation and fusion have become the preferred technique in many centers throughout the world due to simplicity of approach, decreased risk of certain complications and the correction power of pedicle screws. This review attempts to summarize the advantages and disadvantages related to posterior instrumentation and fusion in adolescent idiopathic scoliosis.
Classification of adolescent idiopathic scoliosis (AIS)
Authors: Ovadia Dror
Published: December 2012

In 1983 Howard King presented his classification system for adolescent idiopathic scoliosis (AIS) based on the experience with Harrington rod instrumentation. Curves were divided into five types and guidelines and recommendations for which levels should be instrumented were given to preserve motion as much as possible. As segmental instrumentation systems began to gain favor over the Harrington rods this system failed and led to the development of a new classification system which was presented by Lawrence Lenke in 2001. In order to define a curve type by the Lenke classification, one must identify the curve type, the lumbar modifier and, for the first time in any classification system for scoliosis, the sagittal profile was also included. The Lenke classification showed higher inter and intra-reliability compared to the King classification. It also provided a better and more reliable tool to assist surgeons in choosing the best method of treatment for each curve pattern. Although the Lenke classification is more comprehensive and reliable than the King classification it is still far from perfect. It does not address the rotational component of the deformity. New technologies which provide three-dimensional (3D) reconstruction of the spine may serve as a basis for a truly 3D classification of scoliosis and for new therapeutic concepts.
Osteonecrosis of the femoral head in childhood malignancy
Authors: Mayer Stephanie W. , Mayer Braden K. , Mack Aldridge J. , Urbaniak James R. , Fitch Robert D. , Lark Robert K.
Published: December 2012

Purpose

Children undergoing chemotherapeutic treatment of malignancies have up to a 9 % incidence of osteonecrosis. The purpose of this article is to determine the time from initiation of chemotherapy to the onset of symptoms and the diagnosis of osteonecrosis of the femoral head in this patient population.

Methods

A retrospective review of the records of 18 patients (29 hips) under 21 years of age with both a diagnosis of osteonecrosis of the femoral head and childhood onset malignancy was undertaken to determine the time from initiation of chemotherapy to the onset of symptoms and diagnosis of osteonecrosis of the femoral head.

Results

Mean time from initiation of chemotherapy to the onset of pain was 18.8 months (8.0–49.1). The mean time from development of pain to diagnosis of osteonecrosis was 3.9 months (−13.1 to 25). The mean overall time from initiation of chemotherapy to diagnosis of osteonecrosis was 22.7 months (9.0–54.1). 11/18 patients had bilateral disease. 16/18 patients (21/29 hips) had already progressed to stage 4 osteonecrosis at the time of diagnosis.

Conclusions

There was a high incidence of stage 4 or greater osteonecrosis at the time of diagnosis. Providers caring for these patients should be aware of the potential for osteonecrosis, and the need for prompt diagnosis and referral to an orthopedic surgeon. Screening with advanced imaging studies may be warranted for children undergoing chemotherapeutic regimens for childhood malignancy to prevent delay in the diagnosis and management of this process so that joint preservation therapies remain an option.
Research and standardization in Alzheimer's trials: Reaching international consensus
Authors: Carrillo Maria C. , Rowe Christopher C. , Szoeke Cassandra , Masters Colin L. , Ames David , O'Meara Tim , Macaulay S. Lance , Milner Andrew , Ellis Kathryn A. , Maruff Paul , Rainey‐Smith Stephanie R. , Martins Ralph N. , Bain Lisa J. , Head Richard J.
Published: December 2012

Alzheimer's disease (AD) is an epidemic facing the entire world. Increased knowledge gained during the past 25 years indicates that AD falls along a clinical and neuropathological spectrum represented as a continuum that extends from preclinical disease in which there are no symptoms, through early symptomatic phases, and finally to AD dementia. The Alzheimer's research community recognizes that imaging, body fluids, and cognitive biomarkers contribute to enhanced diagnostic confidence for AD. There has also been emerging consensus regarding the use of AD biomarkers in clinical trials. The use of biomarkers in clinical trials and practice is hampered by the lack of standardization. In response to the emerging need for standardization, an international meeting of AD researchers was held in Melbourne, Australia, in March 2012 to bring together key researchers, clinicians, industry, and regulatory stakeholders with the aim of generating consensus on standardization and validation of cognitive, imaging, and fluid biomarkers, as well as lifestyle parameters used in research centers worldwide.
High-order feature-based mixture models of classification learning predict individual learning curves and enable personalized teaching
Authors: Cohen Yarden , Schneidman Elad
Published: December 2012

Pattern classification learning tasks are commonly used to explore learning strategies in human subjects. The universal and individual traits of learning such tasks reflect our cognitive abilities and have been of interest both psychophysically and clinically. From a computational perspective, these tasks are hard, because the number of patterns and rules one could consider even in simple cases is exponentially large. Thus, when we learn to classify we must use simplifying assumptions and generalize. Studies of human behavior in probabilistic learning tasks have focused on rules in which pattern cues are independent, and also described individual behavior in terms of simple, single-cue, feature-based models. Here, we conducted psychophysical experiments in which people learned to classify binary sequences according to deterministic rules of different complexity, including high-order, multicue-dependent rules. We show that human performance on such tasks is very diverse, but that a class of reinforcement learning-like models that use a mixture of features captures individual learning behavior surprisingly well. These models reflect the important role of subjects’ priors, and their reliance on high-order features even when learning a low-order rule. Further, we show that these models predict future individual answers to a high degree of accuracy. We then use these models to build personally optimized teaching sessions and boost learning.
‘Every child%s birthright'? Democratic entitlement and the role of canonical literature in the English National Curriculum
Authors: Coles Jane
Published: December 2012

In the current government%s ‘Great Books' approach to the National Curriculum for English lies an apparent desire for all school students to benefit from access to a shared ‘cultural heritage', where compulsory knowledge of Shakespeare and other canonical writers is in itself assumed to be a transformative and democratising process. With reference to qualitative classroom‐based research focusing on year 9 and 10 students' experience of Shakespeare at Key Stage 3 and Key Stage 4, this article questions that assumption. Drawing on classroom and interview data from two London comprehensive schools, it suggests that for many students it has been an experience that serves to exclude, a reproduction of existing socio‐cultural differences. Ultimately, even in classrooms where teachers attempt to construct Shakespeare pedagogically as ‘active', the process of reading may remain a passive one, where textual meanings are ultimately almost entirely mediated by teachers, mindful of ensuring all students are afforded ‘access' to the text. This article argues that Shakespeare's iconic status and the authority of the text thus remain largely intact, a disabling process for some students.
Lkb1 takes different paths to morphogenesis
Authors: Short Ben
Published: December 2012

Study uses chemical genetics and embryonic explants to reveal kinase’s tissue-specific functions.
Li-Huei Tsai: I well remember
Authors: Sedwick Caitlin
Published: December 2012

Tsai studies how Cdk5 activity affects brain development, learning, and memory.
Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival
Authors: Kim Hyung Joon , Prasad Vikram , Hyung Seok-Won , Lee Zang Hee , Lee Sang-Won , Bhargava Aditi , Pearce David , Lee Youngkyun , Kim Hong-Hee
Published: December 2012

The precise regulation of Ca2+ dynamics is crucial for proper differentiation and function of osteoclasts. Here we show the involvement of plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 in osteoclastogenesis. In immature/undifferentiated cells, PMCAs inhibited receptor activator of NF-κB ligand–induced Ca2+ oscillations and osteoclast differentiation in vitro. Interestingly, nuclear factor of activated T cell c1 (NFATc1) directly stimulated PMCA transcription, whereas the PMCA-mediated Ca2+ efflux prevented NFATc1 activation, forming a negative regulatory loop. PMCA4 also had an anti-osteoclastogenic effect by reducing NO, which facilitates preosteoclast fusion. In addition to their role in immature cells, increased expression of PMCAs in mature osteoclasts prevented osteoclast apoptosis both in vitro and in vivo. Mice heterozygous for PMCA1 or null for PMCA4 showed an osteopenic phenotype with more osteoclasts on bone surface. Furthermore, PMCA4 expression levels correlated with peak bone mass in premenopausal women. Thus, our results suggest that PMCAs play important roles for the regulation of bone homeostasis in both mice and humans by modulating Ca2+ signaling in osteoclasts.
The chromatin remodeler p400 ATPase facilitates Rad51-mediated repair of DNA double-strand breaks
Authors: Courilleau Céline , Chailleux Catherine , Jauneau Alain , Grimal Fanny , Briois Sébastien , Boutet-Robinet Elisa , Boudsocq François , Trouche Didier , Canitrot Yvan
Published: December 2012

DNA damage signaling and repair take place in a chromatin context. Consequently, chromatin-modifying enzymes, including adenosine triphosphate–dependent chromatin remodeling enzymes, play an important role in the management of DNA double-strand breaks (DSBs). Here, we show that the p400 ATPase is required for DNA repair by homologous recombination (HR). Indeed, although p400 is not required for DNA damage signaling, DNA DSB repair is defective in the absence of p400. We demonstrate that p400 is important for HR-dependent processes, such as recruitment of Rad51 to DSB (a key component of HR), homology-directed repair, and survival after DNA damage. Strikingly, p400 and Rad51 are present in the same complex and both favor chromatin remodeling around DSBs. Altogether, our data provide a direct molecular link between Rad51 and a chromatin remodeling enzyme involved in chromatin decompaction around DNA DSBs.
Tao controls epithelial morphogenesis by promoting Fasciclin 2 endocytosis
Authors: Gomez Juan Manuel , Wang Ying , Riechmann Veit
Published: December 2012

Regulation of epithelial cell shape, for example, changes in relative sizes of apical, basal, and lateral membranes, is a key mechanism driving morphogenesis. However, it is unclear how epithelial cells control the size of their membranes. In the epithelium of the Drosophila melanogaster ovary, cuboidal precursor cells transform into a squamous epithelium through a process that involves lateral membrane shortening coupled to apical membrane extension. In this paper, we report a mutation in the gene Tao, which resulted in the loss of this cuboidal to squamous transition. We show that the inability of Tao mutant cells to shorten their membranes was caused by the accumulation of the cell adhesion molecule Fasciclin 2, the Drosophila N-CAM (neural cell adhesion molecule) homologue. Fasciclin 2 accumulation at the lateral membrane of Tao mutant cells prevented membrane shrinking and thereby inhibited morphogenesis. In wild-type cells, Tao initiated morphogenesis by promoting Fasciclin 2 endocytosis at the lateral membrane. Thus, we identify here a mechanism controlling the morphogenesis of a squamous epithelium.
Cab45 is required for Ca2+-dependent secretory cargo sorting at the trans-Golgi network
Authors: von Blume Julia , Alleaume Anne-Marie , Kienzle Christine , Carreras-Sureda Amado , Valverde Miguel , Malhotra Vivek
Published: December 2012

Ca2+ import into the lumen of the trans-Golgi network (TGN) by the secretory pathway calcium ATPase1 (SPCA1) is required for the sorting of secretory cargo. How is Ca2+ retained in the lumen of the Golgi, and what is its role in cargo sorting? We show here that a soluble, lumenal Golgi resident protein, Cab45, is required for SPCA1-dependent Ca2+ import into the TGN; it binds secretory cargo in a Ca2+-dependent reaction and is required for its sorting at the TGN.
Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways
Authors: Lo Bryan , Strasser Geraldine , Sagolla Meredith , Austin Cary D. , Junttila Melissa , Mellman Ira
Published: December 2012

The tumor suppressor Lkb1/STK11/Par-4 is a key regulator of cellular energy, proliferation, and polarity, yet its mechanisms of action remain poorly defined. We generated mice harboring a mutant Lkb1 knockin allele that allows for rapid inhibition of Lkb1 kinase. Culturing embryonic tissues, we show that acute loss of kinase activity perturbs epithelial morphogenesis without affecting cell polarity. In pancreas, cystic structures developed rapidly after Lkb1 inhibition. In lung, inhibition resulted in cell-autonomous branching defects. Although the lung phenotype was rescued by an activator of the Lkb1 target adenosine monophosphate–activated kinase (AMPK), pancreatic cyst development was independent of AMPK signaling. Remarkably, the pancreatic phenotype evolved to resemble precancerous lesions, demonstrating that loss of Lkb1 was sufficient to drive the initial steps of carcinogenesis ex vivo. A similar phenotype was induced by expression of mutant K-Ras with p16/p19 deletion. Combining culture of embryonic tissues with genetic manipulation and chemical genetics thus provides a powerful approach to unraveling developmental programs and understanding cancer initiation.
Mitotic spindle (DIS)orientation and DISease: Cause or consequence?
Authors: Noatynska Anna , Gotta Monica , Meraldi Patrick
Published: December 2012

Correct alignment of the mitotic spindle during cell division is crucial for cell fate determination, tissue organization, and development. Mutations causing brain diseases and cancer in humans and mice have been associated with spindle orientation defects. These defects are thought to lead to an imbalance between symmetric and asymmetric divisions, causing reduced or excessive cell proliferation. However, most of these disease-linked genes encode proteins that carry out multiple cellular functions. Here, we discuss whether spindle orientation defects are the direct cause for these diseases, or just a correlative side effect.
Cell height: Tao rising
Authors: Cai Liang , Mostov Keith E.
Published: December 2012

During oogenesis in Drosophila melanogaster, the cells in the follicular epithelium of the ovary undergo a transition from a cuboidal to a squamous shape. In this issue, Gomez et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201207150) show that the kinase Tao promotes the endocytosis of the cell adhesion molecule Fasciclin 2 from the lateral surface of the cell and is critical for the cuboidal to squamous cell shape transition. Their results indicate that Tao is rising as a regulator of cell height.
Binary mass ratios: system mass not primary mass
Authors: Goodwin Simon P.
Published: December 2012

Binary properties are usually expressed (for good observational reasons) as a function of primary mass. It has been found that the distribution of companion masses – the mass ratio distribution – is different for different primary masses. We argue that system mass is the more fundamental physical parameter to use. We show that if system masses are drawn from a log-normal mass function, then the different observed mass ratio distributions as a function of primary mass, from M-dwarfs to A-stars, are all consistent with a universal, flat, system mass ratio distribution. We also show that the brown dwarf mass ratio distribution is not drawn from the same flat distribution, suggesting that the process which decides upon mass ratios is very different in brown dwarfs and stars.
The supernova-regulated ISM – II. The mean magnetic field
Authors: Gent F. A. , Shukurov A. , Sarson G. R. , Fletcher A. , Mantere M. J.
Published: December 2012

The origin and structure of the magnetic fields in the interstellar medium of spiral galaxies is investigated with 3D, non-ideal, compressible magnetohydrodynamic simulations, including stratification in the galactic gravity field, differential rotation and radiative cooling. A rectangular domain, 1 × 1 × 2 kpc3 in size, spans both sides of the galactic mid-plane. Supernova explosions drive transonic turbulence. A seed magnetic field grows exponentially to reach a statistically steady state within 1.6 Gyr. Following Germano (1992), we use volume averaging with a Gaussian kernel to separate magnetic field into a mean field and fluctuations. Such averaging does not satisfy all Reynolds rules, yet allows a formulation of mean-field theory. The mean field thus obtained varies in both space and time. Growth rates differ for the mean-field and fluctuating field and there is clear scale separation between the two elements, whose integral scales are about 0.7 and 0.3 kpc, respectively.
Multiple stellar-mass black holes in globular clusters: theoretical confirmation
Authors: Sippel Anna C. , Hurley Jarrod R.
Published: December 2012

While tens or hundreds of stellar-remnant black holes (BHs) are expected to form in globular star clusters, it is still unclear how many of those will be retained upon formation, and how many will be ejected through subsequent dynamical interactions. No such BHs have been found in any Milky Way globular cluster until the recent discovery of stellar-mass BHs in the globular cluster M22 (NGC 6656) with now an estimated population of 5–100 BHs. We present a direct N-body model of a star cluster of the same absolute and dynamical age as M22. Imposing an initial retention fraction of ≈10 per cent for BHs, 16 stellar-remnant BHs are retained at a cluster age of 12 Gyr, in agreement with the estimate for M22. Of those 16 BHs, two are in a binary system with a main-sequence star each while also one pure BH binary is present. We argue that multiple BHs can be present in any Milky Way cluster with an extended core radius, such as M22 or the model presented here.
A Political Theory of Populism
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Authors: Acemoglu Daron , Egorov Georgy , Sonin Konstantin
Published: December 2012

When voters fear that politicians may be influenced or corrupted by the rich elite, signals of integrity are valuable. As a consequence, an honest politician seeking reelection chooses “populist” policies—that is, policies to the left of the median voter—as a way of signaling that he is not beholden to the interests of the right. Politicians that are influenced by right-wing special interests respond by choosing moderate or even left-of-center policies. This populist bias of policy is greater when the value of remaining in office is higher for the politician; when there is greater polarization between the policy preferences of the median voter and right-wing special interests; when politicians are perceived as more likely to be corrupt; when there is an intermediate amount of noise in the information that voters receive; when politicians are more forward-looking; and when there is greater uncertainty about the type of the incumbent. We also show that soft term limits may exacerbate, rather than reduce, the populist bias of policies.
RAPIDLY ENLARGING CHOROIDAL MELANOMA
Authors: Walia Harpreet S. , Shah Sejal D. , Walia Sandeep S. , Pavan Peter R. , Margo Curtis E.
Published: December 2012

Purpose:

The purpose of this study was to describe a case of a rapidly enlarging choroidal melanoma that necessitated perioperative adjustment in treatment.

Methods:

Observational case report.

Results:

A 48-year-old white woman presented with decreased vision and floaters and was found to have a choroidal melanoma in her left eye. After discussion of risks and benefits of treatment, the patient elected radioactive plaque insertion. Intraoperative examination revealed that the choroidal melanoma had increased in height precluding plaque treatment.

Conclusion:

This case highlights the importance of intraocular examination and an informed consent that provides contingency therapies at the time of surgery.
CYTOMEGALOVIRUS RETINITIS IN DYSKERATOSIS CONGENITA
Authors: Haug Sara , Randhawa Sandeep , Fu Arthur , McDonald H. Richard
Published: December 2012

Purpose:

The purpose of this study was to report a case of cytomegalovirus retinitis in the setting of dyskeratosis congenita.

Methods:

Case report and literature review.

Results:

A 23-year-old woman who had peripheral occlusive retinal vasculopathy and neovascularization as a result of pancytopenia caused by bone marrow failure also developed cytomegalovirus retinitis. She had been diagnosed with dyskeratosis congenita, which had caused the bone marrow failure and pancytopenia.

Conclusion:

Dyskeratosis congenita is a multisystem disorder that causes bone marrow failure. It can have retinal manifestations in the form of peripheral proliferative retinopathy and retinitis.
PARASITE IN A YOUNG GIRL FROM VIETNAM PRESENTING AS A GOLDEN FOVEAL LESION
Authors: Khatibi Azadeh , Amini Payam , Goldbaum Michael H.
Published: December 2012

Purpose:

To report a case of likely subretinal foveal parasite, either ophthalmomyiasis from botfly infestation, Angiostrongylus or Gnathostoma.

Methods:

Observational case report of a patient with decreased vision in the left eye since age 4, with examination showing a golden subretinal foveal lesion. She was monitored up to age 24.

Results:

A young woman originally from Vietnam presented at age 11 with vision loss in the left eye since age 4 after a severe febrile illness. Fundus examination revealed a subretinal golden foveal lesion. History, angiography, and spectral domain optical coherence tomography revealed the possibility of parasitic infestation with an entrance site.

Conclusion:

In patients with focal lesions of unknown etiology, careful history, exam, angiography and OCT may indicate a parasitic organism and the entrance site.