bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of the hedgehog signaling pathway contributes to the hair follicle cycling deficiency in Vdr knockout mice
Authors: Teichert Arnaud , Elalieh Hashem , Bikle Daniel
Published: May 2010

Mice null for the Vitamin D receptor (VdrKO) have a disrupted first hair follicle cycle and aborted subsequent hair follicle cycling. We examined the expression of different markers and mediators of hair follicle cycling in the hair follicle of the VdrKO mouse during days 13–22 when the hair follicle normally initiates and completes the first catagen. We compared the expression of those genes in mice with a nonsense mutation in hairless (Rhino), which have a similar alopecia phenotype, and to Cyp27b1 null mice which are deficient in the production of 1,25(OH)2D3, the Vdr ligand, but display normal hair follicle cycling. Our results demonstrate the down regulation of hair follicle markers and the alteration of expression of hedgehog (Hh), Wnt, Fgf, and Tgfβ pathways in VdrKO and Rhino mice, but not in Cyp27b1KO mice. Treatment of VdrKO mice with an agonist to the Hh pathway partially restored hair follicle cycling, suggesting a role of this pathway in the regulation of hair follicle cycling by VDR. These results suggest that Vdr regulates directly or indirectly the expression of genes required for hair follicle cycling, including Hh signaling, independent of 1,25(OH)2D3. J. Cell. Physiol. 225: 482–489, 2010. © 2010 Wiley‐Liss, Inc.
MicroRNA‐1 inhibits myocardin‐induced contractility of human vascular smooth muscle cells
Authors: Jiang Yulan , Yin Hao , Zheng Xi‐Long
Published: May 2010

Myocardin, a cofactor of serum response factor (SRF), specifically induces the expression of contractile proteins to promote differentiation and contractile phenotype of smooth muscle cells (SMCs). SRF directly induces the transcription of microRNA‐1 (miR‐1) in cardiac and skeletal muscle precursor cells and miR‐1 promotes the skeletal muscle differentiation and modulates cardiac hypertrophy. We aimed to examine whether miR‐1 plays a role in the regulation of smooth muscle contractility. We found that miR‐1 expression was induced by myocardin overexpression in human aortic SMCs. In a collagen lattice contraction assay using SMCs harboring a doxycycline‐inducible expression system for myocardin, we found that myocardin expression increased the contractility of SMCs, which was significantly inhibited by exogenous miR‐1. Our further studies revealed that exogenous miR‐1, which did not affect myocardin or SRF expression, suppressed the expression of contractile proteins, such as α‐SMA and SM22, and impaired the actin cytoskeletal organization. Taken together, our results have revealed that myocardin induces miR‐1 expression, which represses the expression of contractile proteins and thereby inhibits the contractility of SMCs. Therefore, our findings suggest a role of miR‐1 in the negative feedback loop in the regulation of contractility induced by myocardin. J. Cell. Physiol. 225: 506–511, 2010. © 2010 Wiley‐Liss, Inc.
RETRACTED: Impact of histone deacetylase inhibitors SAHA and MS‐275 on DNA repair pathways in human mesenchymal stem cells
Authors: Di Bernardo Giovanni , Alessio Nicola , Dell'Aversana Carmela , Casale Fiorina , Teti Diana , Cipollaro Marilena , Altucci Lucia , Galderisi Umberto
Published: May 2010

Histone deacetylase inhibitors (HDACis) have received considerable attention for their anti‐tumoral properties. We report here the effects of two HDACis, SAHA and MS‐275, on the biology of mesenchymal stem cells (MSCs). It is well known that HDACis trigger both DNA damage responses and actual DNA damage in cancer cells. On this premise, we evaluated HDACis influence on DNA damage pathways in MSCs. We analyzed a panel of genes involved in the regulation of base and nucleotide excision repair, mismatch repair, and double strand break repair. That a majority of the analyzed genes displayed significant expression changes upon incubation with SAHA or MS‐275 suggested that regulation of their expression is greatly affected by HDACis. The complex expression pattern, with some genes up‐regulated and other under‐expressed, did not allow to foresee whether these changes allow cells cope with stressful DNA damaging stimuli. Furthermore, we evaluated the biological outcome following treatment of MSCs with DNA damaging agents (H2O2 and UV) in presence of HDACis. In these settings, MSCs treated with H2O2 or UV radiation underwent apoptosis and/or senescence, and pre‐incubation with HDACi exacerbated cell death phenomena. Accordingly, the number of cells harboring 8‐oxo‐7,8‐dihydroguanine (8oxodG), a hallmark of DNA oxidative damage, was significantly higher in samples incubated with HDACis compared to controls. In summary, our findings suggest that SAHA and MS‐275, even at low effective doses, can alter the biology of MSCs, diminishing their ability to survive the effects of DNA‐damaging agents. J. Cell. Physiol. 225: 537–544, 2010. © 2010 Wiley‐Liss, Inc.
In vitro differentiation of unrestricted somatic stem cells into functional hepatic‐like cells displaying a hepatocyte‐like glucose metabolism
Authors: Waclawczyk Simon , Buchheiser Anja , Flögel Ulrich , Radke Teja F. , Kögler Gesine
Published: May 2010

The hepatic‐like phenotype resulting from in vitro differentiation of unrestricted somatic stem cells (USSC) derived from human umbilical cord blood (CB) was analyzed with regard to functional and metabolic aspects. USSC can be differentiated into cells of all three germ layers in vitro and in vivo and, although they share many features with mesenchymal stroma cells (MSC), can be distinguished from these by their expression of DLK1 as well as a restricted adipogenic differentiation potential. For the differentiation procedure described herein, a novel three‐stage differentiation protocol resembling embryonic developmental processes of hepatic endoderm was applied. Hepatic pre‐induction was performed by activinA and FGF4 resulting in enhanced SOX17 and FOXA2 expression. Further differentiation was achieved sequentially by retinoic acid, FGF4, HGF, EGF, and OSM resulting in a hepatic endodermal identity, characterized by the expression of AFP and HNF1α. Thereafter, expression of G6PC, ARG1, FBP1, and HNF4α was observed, thus indicating progressive differentiation. Functional studies concerning albumin secretion, urea formation, and cytochrome‐p450‐3A4 (CYP3A4) enzyme activity confirmed the hepatic‐like phenotype. In order to characterize the differentiated cells at a metabolic level, USSC were incubated with [1‐13C]glucose. By tracing the fate of the molecule's label via isotopomer analysis using 13C NMR spectroscopy, formation of both glycogen and some gluconeogenetic activity could be observed providing evidence of a hepatocyte‐like glucose metabolism in differentiated USSC. In conclusion, the results of the present study indicate that USSC represent a stem cell source with a substantial hepatic differentiation capacity which hold the potential for clinical applications. J. Cell. Physiol. 225: 545–554, 2010. © 2010 Wiley‐Liss, Inc.
Food safety and consumer willingness to pay for certified traceable food in China
Authors: Xu Lingling , Wu Linhai
Published: May 2010

BACKGROUND: The September 2008 melamine outbreak in China has adversely affected perceptions of food safety among consumers. This paper presents a survey of the perception of food safety and willingness to pay for certified traceable (CT) food among the citizens of Jiangsu Province. It presents the critical necessity of establishing a food traceability system (FTS) to address possible similar outbreaks in the future.

RESULTS: The results show that 36% of the respondents are strongly dissatisfied with food safety conditions in the province. Only 37% of the respondents have heard of FTS. Among the respondents who chose to buy CT food, 32% were unwilling to shoulder the extra cost. The consumers' overall satisfaction with food safety, awareness of FTS, gender, age, educational level and income are the main determinants of Chinese consumers' willingness to pay for CT food.

CONCLUSION: Based on the results, it is proposed that the Chinese government pay attention to the mentality of its citizens when establishing an FTS and take measures to lift consumers' willingness to pay for CT food. Results of this study will provide valuable insights to developing countries. Copyright © 2010 Society of Chemical Industry
Iterative Shannon Entropy – a Methodology to Quantify the Information Content of Value Range Dependent Data Distributions. Application to Descriptor and Compound Selectivity Profiling
Authors: Wassermann Anne Mai , Vogt Martin , Bajorath Jürgen
Published: May 2010

We introduce an entropy‐based methodology, Iterative Shannon entropy (ISE), to quantify the information contained in molecular descriptors and compound selectivity data sets taking data spread directly into account. The method is applicable to determine the information content of any value range dependent data distribution. An analysis of descriptor information content has been carried out to explore alternative binning schemes for entropy calculation. Using this entropic measure we have profiled 153 compound selectivity data sets for combinations of 68 target proteins belonging to 10 target families. With the ISE measure, we aim to assign high information content to compound data sets that span a wide range of selectivity values and different selectivity relationships and hence correspond to more than one biological phenotype. Target families with high average entropy scores are identified. For members of these families, active compounds display highly differentiated selectivity profiles.
Tensor kernels for simultaneous fiber model estimation and tractography
Authors: Rathi Yogesh , Malcolm James G. , Michailovich Oleg , Westin Carl‐Fredrik , Shenton Martha E. , Bouix Sylvain
Published: May 2010

This paper proposes a novel framework for joint orientation distribution function estimation and tractography based on a new class of tensor kernels. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. In this work, fiber tracking is formulated as recursive estimation: at each step of tracing the fiber, the current estimate of the orientation distribution function is guided by the previous. To do this, second‐and higher‐order tensor‐based kernels are employed. A weighted mixture of these tensor kernels is used for representing crossing and branching fiber structures. While tracing a fiber, the parameters of the mixture model are estimated based on the orientation distribution function at that location and a smoothness term that penalizes deviation from the previous estimate along the fiber direction. This ensures smooth estimation along the direction of propagation of the fiber.

In synthetic experiments, using a mixture of two and three components it is shown that this approach improves the angular resolution at crossings. In vivo experiments using two and three components examine the corpus callosum and corticospinal tract and confirm the ability to trace through regions known to contain such crossing and branching. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Polar Expedition Project and Project Management
Authors: Garel Gilles , Lièvre Pascal
Published: May 2010

This article presents the results of a polar expedition by sea kayak in which the authors participated in 2007. It calls upon the approach of Bruno Latour to describe the forms of socio-technical combinations and the controversies that arose during the course of the project. In addition, the article utilizes the experience of this unique project to draw lessons regarding project management in general: lessons on team makeup, knowledge management, and the relationship between preparation and actual implementation of a given project.
Interleukin‐9 polymorphism in infants with respiratory syncytial virus infection: An opposite effect in boys and girls
Authors: Schuurhof Annemieke , Bont Louis , Siezen Christine L. E. , Hodemaekers Hennie , van Houwelingen Hans C. , Kimman Tjeerd G. , Hoebee Barbara , Kimpen Jan L. L. , Janssen Riny
Published: May 2010

The predominance of severe respiratory syncytial virus (RSV) bronchiolitis in boys compared to girls is well known, but its mechanism is not yet understood. This is the first study focusing on gender‐specific genetic factors affecting the risk of severe RSV infection using a previously described cohort. We determined 347 single‐nucleotide polymorphisms (SNPs) in 470 children hospitalized for RSV infection, their parents, and 1,008 random population controls. We tested if these SNPs exerted a different effect in boys and girls by performing statistical interaction tests. Only one SNP (rs2069885) had a gender‐specific significant association with RSV infection, severe enough to require hospitalization (P‐value 0.00057). The major allele of this structural polymorphism in the interleukin (IL)‐9 gene is associated with an increased susceptibility to severe RSV infection in boys, while there is a decreased susceptibility in girls. Haplotype analysis of two SNPs in the IL‐9 gene (rs2069885 and rs1799962) showed overrepresentation of the TT haplotype in girls with severe RSV bronchiolitis requiring hospitalization indicating that this is the haplotype conferring the highest risk in girls. In conclusion, the IL‐9 genetic polymorphism (rs2069885) has an opposite effect on the risk of severe RSV bronchiolitis in boys and girls. Although so far a difference in IL‐9 production in boys and girls has not been reported, this study may help in explaining the different risks of severe RSV bronchiolitis in boys and girls. Pediatr Pulmonol. 2010; 45:608–613. © 2010 Wiley‐Liss, Inc.
Dipolar glass phase in ferrielectrics: CuInP2S6 and Ag0.1Cu0.9InP2S6 crystals
Authors: Dziaugys Andrius , Banys Juras , Macutkevic Jan , Sobiestianskas Ricardas , Vysochanskii Yulian
Published: May 2010

The dielectric properties of CuInP2S6 and Ag0.1Cu0.9InP2S6 crystals were investigated in wide frequency (20 Hz–3 GHz) and temperature ranges (25–360 K). The low frequencies dielectric spectra at high temperatures are highly influenced by the high ionic conductivity. The temperature dependences of the static dielectric permittivity and the mean relaxation time reveal the first order order–disorder ferrielectric phase transition at Tc = 288 K in Ag0.1Cu0.9InP2S6. The conductivity and its activation energy exhibit only a weak change close to the ferrielectric phase transition temperature in both investigated crystals. The freezing phenomena in CuInP2S6 and Ag0.1Cu0.9InP2S6 revealed the complex dielectric permittivity behaviour characteristic for transition into dipolar glass state.
Aqueous synthesis and characterization of nearly monodispersed ZnS nanocrystals
Authors: Azizian‐Kalandaragh Yashar , Khodayari Ali
Published: May 2010

An ultrasound‐assisted solution‐phase process has been applied for the aqueous synthesis of zinc sulfide nanocrystals in the presence of 3‐mercaptopropionic acid (3‐MPA) as a capping agent. The synthesis procedure was carried out by using two reagents: zinc chloride and sodium sulfide. Spherical shaped nanoparticles were agglomerated in the form of nanoclusters were observed. Obtained crystalline materials were found without the need of a post‐synthesis treatment. The preparative conditions such as precursor concentrations, pH, and washing materials were optimized. The average crystalline size of ZnS nanostructures has been analyzed by X‐ray diffraction (XRD) pattern and estimated to be 4.7 nm. The energy dispersive X‐ray analysis (EDAX) reveals the average atomic percentage of Zn/S was 50:50, showing that the preparation is exactly stoichiometric. Optical measurements indicate a direct band gap of about 4.27 eV. There was observed a blue shift of about 0.57 eV, in comparison to its bulk value due to quantum confinement effects of electrons and holes.
(In)AlGaN deep ultraviolet light emitting diodes with optimized quantum well width
Authors: Kolbe Tim , Sembdner Toni , Knauer Arne , Kueller Viola , Rodriguez Hernan , Einfeldt Sven , Vogt Patrick , Weyers Markus , Kneissl Michael
Published: May 2010

The effect of the quantum well (QW) width on the light output and efficiency of ultraviolet (UV) light emitting diodes (LEDs) has been investigated. The carrier injection in the devices is simulated and compared with electroluminescence (EL) measurements. The light output power depends clearly on the QW thickness. The highest output power has been found for the LEDs with a QW thickness of 2.2 nm. This effect is attributed to the trade‐off between electron and hole wave function overlap and carrier concentration in the active region which are triggered by the quantum confined Stark effect.
Direct analysis of pharmaceutical tablet formulations using matrix‐assisted laser desorption/ionisation mass spectrometry imaging
Authors: Earnshaw Caroline J. , Carolan Vikki A. , Richards Don S. , Clench Malcolm R.
Published: May 2010

Matrix‐Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging (MALDI MSI) has been used to directly analyse a range of tablets in order to assess the homogeneity of the active drug compound throughout the excipients contained within the tablets studied. The information gained from the imaging experiments can be used to improve and gain a greater understanding of the manufacturing process; such knowledge will enable improvements in finished product quality to make safer and more efficacious tablet formulations. Commercially available and prescription tablet formulations have been analysed, including aspirin, paracetamol, sildenafil citrate (Viagra®) and a batch of tablets in development (tablet X: placebo; 1 mg; 3 mg and 6 mg). MALDI MSI provides semi‐quantitative information that is related to ion abundance, therefore Principal Component Analysis (PCA), a multivariate analysis technique, has been used to differentiate between tablets containing different amounts of active drug ingredient. Aspects of sample preparation have also been investigated with regard to tablet shape and texture. The results obtained indicate that MALDI MSI can be used effectively to analyse the spatial distribution of the active pharmaceutical component (API) in pharmaceutical tablet formulations. Copyright © 2010 John Wiley & Sons, Ltd.
δ13C and δ2H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane
Authors: Collins Michael , Salouros Helen , Cawley Adam T. , Robertson James , Heagney Aaron C. , Arenas‐Queralt Andrea
Published: May 2010

Previous work in these laboratories and by Butzenlechner et al. and Culp et al. has demonstrated that the δ2H isotope value of industrial benzaldehyde produced by the catalytic oxidation of toluene is profoundly positive, usually in the range +300‰ to +500‰. Synthetic routes leading to amphetamine, methylamphetamine or their precursors and commencing with such benzaldehyde may be expected to exhibit unusually positive δ2H values. Results are presented for δ13C and δ2H isotope values of 1‐phenyl‐2‐nitropropene synthesized from an industrial source of benzaldehyde, having a positive δ2H isotope value, by a Knoevenagel condensation with nitroethane. Results are also presented for δ13C and δ2H isotope values for amphetamine prepared from the resulting 1‐phenyl‐2‐nitropropene. The values obtained were compared with δ13C and δ2H isotope values obtained for an amphetamine sample prepared using a synthetic route that did not involve benzaldehyde. Finally, results are presented for samples of benzaldehyde, 1‐phenyl‐2‐nitropropene and amphetamine that had been seized at a clandestine amphetamine laboratory. Copyright © 2010 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.
Toward milk speciation through the monitoring of casein proteotypic peptides
Authors: Cuollo Marina , Caira Simonetta , Fierro Olga , Pinto Gabriella , Picariello Gianluca , Addeo Francesco
Published: May 2010

The possibility of detecting extraneous milk in singles species cheese‐milk has been explored. A mass spectrometry (MS)‐based procedure has been developed to detect 'signature peptides', corresponding to the predefined subset of 'proteotypic peptides', as matchless analytical surrogates of the parent caseins. Tryptic digests of skimmed milk samples from four species were analyzed by matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) MS. Amongst the candidate signature peptides that are able to differentiate milks from the four species, the αs1‐casein (CN) f8‐22 peptide was selected as a convenient marker for bovine, ovine and water buffalo milk while the f4‐22 peptide was selected as a marker for the two caprine αs1‐CN A and B variants, which differ by a Pro16 (B)‐>Leu16 (A) substitution. MALDI analysis of the digest allowed the detection of αs1‐CN f8‐22 and caprine αs1‐CN f4‐22. The accurate evaluation of caprine milk in a quaternary mixture required the development of a liquid chromatography/electrospray ionization (LC/ESI)‐MS procedure. Five synthetic signature peptide analogues, which differed from their natural counterparts by a single amino acid substitution, were used as internal standards to quantify the αs1‐CN, which was chosen as a reference milk protein, from the different species. The limits of detection were 0.5% (1% for caprine) for either the MALDI or the LC/ESI‐MS method. The isotopic‐label‐free quantification of isoform‐ or variant‐specific signature peptides has disclosed a convenient approach for targeting proteins in complex mixtures. Copyright © 2010 John Wiley & Sons, Ltd.
A gas chromatography/mass spectrometry method for the determination of sildenafil, vardenafil and tadalafil and their metabolites in human urine
Authors: Strano‐Rossi Sabina , Anzillotti Luca , de la Torre Xavier , Botrè Francesco
Published: May 2010

Sildenafil (SDF), vardenafil (VDF) and tadalafil (TDF) are phosphodiesterase type 5 enzyme inhibitors (PDE5Is), used in the treatment of erectile disorders and to improve breathing efficiency in pulmonary hypertension. The increasing incidence of their use among young athletes has drawn the attention of the anti‐doping authorities to the possible abuse of PDE5Is by athletes due to their pharmacological activities. This paper describes a method for the determination in urine of PDE5Is and their metabolites by gas chromatography/mass spectrometry (GC/MS) after liquid/liquid extraction of the analytes from urine and derivatisation to obtain trimethylsilyl derivatives. The metabolic profile was studied on real samples collected from subjects taking PDE5Is (Viagra®, Levitra® or Cialis®); the main urinary metabolites were identified and their MS fragmentation characterized. The sample pre‐treatment and GC/MS conditions for the detection of the metabolites have been optimised. A method for their preliminary screening and subsequent confirmation is described that takes into account the general requirements of a routine doping analysis to be used for the screening of large numbers of samples. The main metabolites identified can be included in a general purpose screening method and all the metabolites in a more specific confirmation method. The method developed has been applied for the screening of PDE5Is in 5000 urine samples. Based on the obtained results, the proposed method appears to be of practical use in analytical and forensic toxicology, including doping analysis. Copyright © 2010 John Wiley & Sons, Ltd.
Ephrins Negatively Regulate Cell Proliferation in the Epidermis and Hair Follicle
Authors: Genander Maria , Holmberg Johan , Frisén Jonas
Published: May 2010

Ephrins and their Eph tyrosine kinase receptors control many processes during embryonic development. They have more recently also been identified as important regulators of proliferation of stem/progenitor cells in the adult brain and intestine and have been implicated in tumorigenesis in a large number of tissues. We here describe the expression of a large number of ephrins and Eph receptors in the adult mouse skin. Disruption of the ephrin-Eph interaction in vivo with antagonists against the A or B class resulted in an approximate doubling of cell proliferation in the hair follicle and epidermis of adult mice. We conclude that ephrins are negative regulators of proliferation in the skin and that blocking the ephrin-Eph interaction may be an attractive strategy for regenerative therapies.
Afferent Loop Obstruction After Distal Gastrectomy with Roux‐en‐Y Reconstruction
Authors: Aoki Masaru , Saka Makoto , Morita Shinji , Fukagawa Takeo , Katai Hitoshi
Published: May 2010

Background

The incidence of afferent loop obstruction after gastrectomy with Roux‐en‐Y reconstruction has not yet been reported. The aim of this study was to elucidate the incidence of afferent loop obstruction after distal gastrectomy with Roux‐en‐Y reconstruction performed through an open approach.

Methods

We conducted a retrospective review of the data of 1908 patients who underwent distal gastrectomy followed by Roux‐en‐Y reconstruction through an open approach between January 1999 and December 2008.

Results

Four patients (0.2%) developed afferent loop obstruction. The median age of the patients, consisting of three men and one woman, was 64 years (range 46–78 years). The cause of the afferent loop obstruction was internal herniation in two patients, adhesion in one patient, and peritoneal recurrence in one patient. The internal herniation occurred at the mesenteric gap in the region of the jejunojejunostomy. The interval between the initial gastrectomies and the emergency operations for afferent loop obstruction ranged from 3 weeks to 2 years (median 5 months). Three of the four patients were symptomatic, with vomiting and abdominal pain. All patients recovered following the emergency operations, and none died of this complication.

Conclusions

Afferent loop obstruction develops rarely after distal gastrectomy with Roux‐en‐Y reconstruction through an open approach. This rare but fatal complication should be considered when a patient complains of abdominal pain and/or vomiting after distal gastrectomy with Roux‐en‐Y reconstruction.
Stenosis of Esophago‐jejuno Anastomosis After Gastric Surgery
Authors: Fukagawa Takeo , Gotoda Takuji , Oda Ichiro , Deguchi Yasunori , Saka Makoto , Morita Shinji , Katai Hitoshi
Published: May 2010

Background

Stenosis of esophago‐jejuno anastomosis is one of the postoperative complications of gastric surgery. This complication usually manifests with the symptom of dysphagia and is treated by endoscopic dilatation. No large‐scale studies have been conducted to determine the incidence of this complication after surgery.

Methods

The data of a total of 1478 consecutive patients who underwent total, proximal, or completion gastrectomy, including esophago‐jejuno anastomosis, between 2000 and 2008 were analyzed retrospectively with a view to determining the incidence of anastomotic stenosis.

Results

Sixty patients (4.1%) developed stenosis of the esophago‐jejuno anastomosis which needed to be treated by endoscopic balloon dilatation. The average interval between the surgery and detection of stenosis was 67.4 days (median = 58.0). Multivariate analysis identified female gender, proximal gastrectomy, use of a narrow‐sized stapler, and the choice of the stapling device as significant factors influencing the risk of development of anastomotic stenosis.

Conclusion

Esophago‐jejuno anastomotic stenosis appears to be a common late postoperative complication after gastric surgery. Endoscopic examination and treatment yielded favorable outcomes in patients complaining of dysphagia after gastric surgery.
Large dilating balloon to allow endoscope insertion for successful endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy (with video)
Authors: Itoi Takao , Sofuni Atsushi , Itokawa Fumihide
Published: May 2010

Background and purpose

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy can be present unique challenges. One of the major obstacles preventing successful ERCP is acute angulation and long afferent loops in patients with Billroth II gastrectomy or Roux‐en‐Y anastomosis. Here, we described a novel technique for successful endoscope insertion using a large dilating balloon.

Methods

The large dilating balloon (maximum diameter 20 mm) is used as an anchor for endoscope insertion (hooking method) in patients with Billroth II gastrectomy in whom no other endoscopes could be advanced into the end of the duodenum or the Roux‐en‐Y anastomosis.

Results

The hooking method allows the endoscope to be advanced into the proximal afferent loop, even in patients with sharp angulation of the Y limb.

Conclusions

To the best of our knowledge, this is the first report on the use of a large dilating balloon for endoscope insertion in patients with surgically altered anatomy, in particular Roux‐en‐Y anastomosis. We believe this technique may be effective for difficult cases like the present case.
Mitochondrial tRNALeu(UUR) mutation m.3302A > G presenting as childhood‐onset severe myopathy: threshold determination through segregation study
Authors: Ballhausen Diana , Guerry Frédéric , Hahn Dagmar , Schaller André , Nuoffer Jean‐Marc , Bonafé Luisa , Jeannet Pierre‐Yves , Jacquemont Sebastien
Published: May 2010

Mitochondrial tRNALeu(UUR) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult‐onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early‐onset myopathy was rapidly progressive. At 8 years, the patient is wheel‐chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non‐affected adults. The phenotypic spectrum of tRNALeu(UUR) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.
Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice
Authors: te Vruchte Danielle , Jeans Aruna , Platt Frances M. , Sillence Daniel John
Published: May 2010

Glycosphingolipid storage diseases are a group of inherited metabolic diseases in which glycosphingolipids accumulate due to their impaired lysosomal breakdown. Splenic B cells isolated from NPC1, Sandhoff, GM1‐gangliosidosis and Fabry disease mouse models showed large (20‐ to 30‐fold) increases in disease specific glycosphingolipids and up to a 4‐fold increase in cholesterol. The magnitude of glycosphingolipid storage was in the order NPC1 > Sandhoff ∼ GM1 gangliosidosis > Fabry. Except for Fabry disease, glycosphingolipid storage led to an increase in the lysosomal compartment and altered glycosphingolipid trafficking. In order to investigate the consequences of storage on B cell function, the levels of surface expression of B cell IgM receptor and its associated components were quantitated in Sandhoff B cells, since they are all raft‐associated on activation. Both the B cell receptor, CD21 and CD19 had decreased cell surface expression. In contrast, CD40 and MHC II, surface receptors that do not associate with lipid rafts, were unchanged. Using a pulse chase biotinylation procedure, surface B cell receptors on a Sandhoff lymphoblast cell line were found to have a significantly decreased half‐life. Increased co‐localization of fluorescently conjugated cholera toxin and lysosomes was also observed in Sandhoff B cells. Glycosphingolipid storage leads to the enhanced formation of lysosomal lipid rafts, altered endocytic trafficking and increased degradation of the B cell receptor.
Beschäftigungssuburbanisierung, Siedlungsstruktur und Berufspendelverkehr: Ergebnisse für deutsche Agglomerationsräume 1999-2007
Authors: Guth Dennis , Holz-Rau Christian , Maciolek Markus , Scheiner Joachim
Published: May 2010

The paper examines the effect of employment suburbanisation on commuter traffic in German metropolitan regions. In order to identify how different urban spatial structures affect commuting behaviour, monocentric (Hamburg, Munich) and polycentric regions (Frankfurt am Main, Stuttgart) are compared. First we focus on the (spatio)structural minimum number of commuters, which is an appropriate measure for the regional jobs housing balance. In the second step we analyze the change of both the commuting volume and the distances covered by commuters. For this purpose, different indicators derived from commuting data are used, allowing us to compare different agglomerations and/or points in time. The analysis is based on commuting data between 1999 and 2007 taken from the German Social Security Statistics.
Estimating the Electoral Effects of Voter Turnout
Authors: HANSFORD THOMAS G. , GOMEZ BRAD T.
Published: May 2010

This article examines the electoral consequences of variation in voter turnout in the United States. Existing scholarship focuses on the claim that high turnout benefits Democrats, but evidence supporting this conjecture is variable and controversial. Previous work, however, does not account for endogeneity between turnout and electoral choice, and thus, causal claims are questionable. Using election day rainfall as an instrumental variable for voter turnout, we are able to estimate the effect of variation in turnout due to across-the-board changes in the utility of voting. We re-examine the Partisan Effects and Two-Effects Hypotheses, provide an empirical test of an Anti-Incumbent Hypothesis, and propose a Volatility Hypothesis, which posits that high turnout produces less predictable electoral outcomes. Using county-level data from the 1948–2000 presidential elections, we find support for each hypothesis. Failing to address the endogeneity problem would lead researchers to incorrectly reject all but the Anti-Incumbent Hypothesis. The effect of variation in turnout on electoral outcomes appears quite meaningful. Although election-specific factors other than turnout have the greatest influence on who wins an election, variation in turnout significantly affects vote shares at the county, national, and Electoral College levels.
Compulsory Voting: A Critical Perspective
Authors: Lever Annabelle
Published: May 2010

Compulsory voting is sometimes thought to be justified in democracies because it promotes high levels of voting and mitigates inequalities of turnout amongst social groups. Proponents of compulsory voting also argue that it helps to prevent the free-riding of non-voters on voters. This article casts a sceptical eye on both arguments. Democratic citizens do not have a duty to promote their self-interest, and their duties to others do not generally require them to vote, or to attend the polls. So, while people are sometimes morally obliged to vote, and to vote one way rather than another, legal compulsion to vote or to turn out is generally unjustified and inconsistent with democratic government.
Simulating activity of the bacterial ribosome
Authors: Trylska Joanna
Published: May 2010

Computational modeling studies that investigate activity of the bacterial ribosome were reviewed. Computational approaches became possible with the availability of three-dimensional atomic resolution structures of the ribosomal subunits. However, due to the enormous size of the system, theoretical efforts to study the ribosome are few and challenging. For example, to extend the simulation timescales to biologically relevant ones, often, reduced models that require tedious parameterizations need to be applied. To that end, modeling of the ribosome focused on its internal dynamics, electrostatic properties, inhibition by antibiotics, polypeptide folding in the ribosome tunnel and assembly mechanisms driving the formation of the small ribosomal subunit.
Protein characterisation by synchrotron radiation circular dichroism spectroscopy
Authors: Wallace B. A.
Published: May 2010

Circular dichroism (CD) spectroscopy is a well-established technique for the study of proteins. Synchrotron radiation circular dichroism (SRCD) spectroscopy extends the utility of conventional CD spectroscopy (i.e. using laboratory-based instruments) because the high light flux from a synchrotron enables collection of data to lower wavelengths, detection of spectra with higher signal-to-noise levels and measurements in the presence of strongly absorbing non-chiral components such as salts, buffers, lipids and detergents. This review describes developments in instrumentation, methodologies and bioinformatics that have enabled new applications of the SRCD technique for the study of proteins. It includes examples of the use of SRCD spectroscopy for providing static and dynamic structural information on molecules, including determinations of secondary structures of intact proteins and domains, assessment of protein stability, detection of conformational changes associated with ligand and drug binding, monitoring of environmental effects, examination of the processes of protein folding and membrane insertion, comparisons of mutant and modified proteins, identification of intermolecular interactions and complex formation, determination of the dispositions of proteins in membranes, identification of natively disordered proteins and their binding partners and examination of the carbohydrate components of glycoproteins. It also discusses how SRCD can be used in conjunction with macromolecular crystallography and other biophysical techniques to provide a more complete picture of protein structures and functions, including how proteins interact with other macromolecules and ligands. This review also includes a discussion of potential new applications in structural and functional genomics using SRCD spectroscopy and future instrumentation and bioinformatics developments that will enable such studies. Finally, the appendix describes a number of computational/bioinformatics resources for secondary structure analyses that take advantage of the improved data quality available from SRCD. In summary, this review discusses how SRCD can be used for a wide range of structural and functional studies of proteins.
Aperiodicity and cofinality for finitely aligned higher-rank graphs
Authors: LEWIN PETER , SIMS AIDAN
Published: May 2010

We introduce new formulations of aperiodicity and cofinality for finitely aligned higher-rank graphs Λ, and prove thatC*(Λ) is simple if and only if Λ is aperiodic and cofinal. The main advantage of our versions of aperiodicity and cofinality over existing ones is that ours are stated in terms of finite paths. To prove our main result, we first characterise each of aperiodicity and cofinality of Λ in terms of the ideal structure ofC*(Λ). In an appendix we show how our new cofinality condition simplifies in a number of special cases which have been treated previously in the literature; even in these settings our results are new.
Diamond aggregation
Authors: KAGER WOUTER , LEVINE LIONEL
Published: May 2010

Internal diffusion-limited aggregation is a growth model based on random walk in ℤd. We study how the shape of the aggregate depends on the law of the underlying walk, focusing on a family of walks in ℤ2 for which the limiting shape is a diamond. Certain of these walks—those with a directional bias toward the origin—have at most logarithmic fluctuations around the limiting shape. This contrasts with the simple random walk, where the limiting shape is a disk and the best known bound on the fluctuations, due to Lawler, is a power law. Our walks enjoy a uniform layering property which simplifies many of the proofs.
Simultaneous Diophantine approximation in the real, complex and p–adic fields.
Authors: BUDARINA NATALIA , DICKINSON DETTA , BERNIK VASILI
Published: May 2010

In this paper it is shown that if the volume sum ∑r = 1∞ Ψ(r) converges for a monotonic function Ψ then the set of points (x, z, w) ∈ ℝ × ℂ × ℚp which simultaneously satisfy the inequalities |P(x)| ≤ H−v1 Ψλ1(H), |P(z)| ≤ H−v2 Ψλ2(H) and |P(w)|p ≤ H−v3 Ψλ3(H) with v1 + 2v2 + v3 = n − 3 and λ1 + 2λ2 + λ3 = 1 for infinitely many integer polynomials P has measure zero.
Invariants of 3-manifolds derived from covering presentations
Authors: HATAKENAKA ERI
Published: May 2010

By a covering presentation of a 3-manifold, we mean a labelled link (i.e., a link with a monodromy representation), which presents the 3-manifold as the simple 4-fold covering space of the 3-sphere branched along the link with the given monodromy. It is known that two labelled links present a homeomorphic 3-manifold if and only if they are related by a finite sequence of some local moves. This paper presents a method for constructing topological invariants of 3-manifolds based on their covering presentations. The proof of the topological invariance is shown by verifying the invariance under the local moves. As an example of such invariants, we present the Dijkgraaf–Witten invariant of 3-manifolds.
Hantavirus outbreak in Western Europe: reservoir host infection dynamics related to human disease patterns
Authors: TERSAGO K. , VERHAGEN R. , VAPALAHTI O. , HEYMAN P. , DUCOFFRE G. , LEIRS H.
Published: May 2010

Within Europe, Puumala virus (PUUV) is the causal agent of nephropathia epidemica (NE) in humans, a zoonotic disease with increasing significance in recent years. In a region of Belgium with a historically high incidence of NE, bank voles (the PUUV reservoir hosts), were monitored for PUUV IgG antibody prevalence in nine study sites before, during, and after the highest NE outbreak recorded in Belgium in 2005. We found that the highest numbers of PUUV IgG-positive voles coincided with the peak of NE cases at the regional level, indicating that a PUUV epizootic in bank voles directly led to the NE outbreak in humans. On a local scale, PUUV infection in voles was patchy and not correlated to NE incidence before the epizootic. However, during the epizootic period PUUV infection spread in the vole populations and was significantly correlated to local NE incidence. Initially, local bank-vole numbers were positively associated with local PUUV infection risk in voles, but this was no longer the case after the homogeneous spreading of PUUV during the PUUV outbreak.
Mill on the Harm in Not Voting
Authors: BROWN D. G.
Published: May 2010

Christopher Miles Coope offers a letter, drafted by Helen Taylor but certified by Mill, in which Mill asserts the duty to vote, as evidence that he could not have regarded harmfulness to others as a necessary condition of moral wrongness. But it is clear that Mill regarded the duty to vote as one of imperfect obligation, and the wrongness of not fulfilling it as a matter roughly of not doing enough, in this case not doing one's fair share. He has room for the common-sense harmlessness of staying at home. At the same time he grounds political duties in the harmfulness of neglecting the power of legislation and in the possibility, consistently maintained, that one can harm by inaction. Mill's view, central to his relation between morality and liberty, remains at work here, while also suggesting reflections on the peculiarity of his conception of harm.
Intertemporal Disagreement and Empirical Slippery Slope Arguments
Authors: DOUGLAS THOMAS
Published: May 2010

One prevalent type of slippery slope argument has the following form: (1) by doing some initial act now, we will bring it about that we subsequently do some more extreme version of this act, and (2) we should not bring it about that we do this further act, therefore (3) we should not do the initial act. Such arguments are frequently regarded as mistaken, often on the grounds that they rely on speculative or insufficiently strong empirical premises. In this article I point out another location at which these arguments may go wrong: I argue that, in their standard form, the truth of their empirical premises constitutes evidence for the falsity of their normative premises. If we will, as predicted, do the further act in the future, this gives us at least a prima facie reason to believe that the performance of this further act would be good, and thus something we should try to bring about. I end by briefly assessing the dialectic implications of my argument. I delineate a subset of slippery slope arguments against which my objection may be decisive, consider how the proponents of such arguments may evade my objection by adding further premises, and examine the likely plausibility of these additional premises.
Exponential integrators
Authors: Hochbruck Marlis , Ostermann Alexander
Published: May 2010

In this paper we consider the construction, analysis, implementation and application of exponential integrators. The focus will be on two types of stiff problems. The first one is characterized by a Jacobian that possesses eigenvalues with large negative real parts. Parabolic partial differential equations and their spatial discretization are typical examples. The second class consists of highly oscillatory problems with purely imaginary eigenvalues of large modulus. Apart from motivating the construction of exponential integrators for various classes of problems, our main intention in this article is to present the mathematics behind these methods. We will derive error bounds that are independent of stiffness or highest frequencies in the system.

Since the implementation of exponential integrators requires the evaluation of the product of a matrix function with a vector, we will briefly discuss some possible approaches as well. The paper concludes with some applications, in which exponential integrators are used.
Inverse problems: A Bayesian perspective
Authors: Stuart A. M.
Published: May 2010

The subject of inverse problems in differential equations is of enormous practical importance, and has also generated substantial mathematical and computational innovation. Typically some form of regularization is required to ameliorate ill-posed behaviour. In this article we review the Bayesian approach to regularization, developing a function space viewpoint on the subject. This approach allows for a full characterization of all possible solutions, and their relative probabilities, whilst simultaneously forcing significant modelling issues to be addressed in a clear and precise fashion. Although expensive to implement, this approach is starting to lie within the range of the available computational resources in many application areas. It also allows for the quantification of uncertainty and risk, something which is increasingly demanded by these applications. Furthermore, the approach is conceptually important for the understanding of simpler, computationally expedient approaches to inverse problems.
A TEST OF THE GARCH(1, 1) SPECIFICATION FOR DAILY STOCK RETURNS
Authors: Ashley Richard A. , Patterson Douglas M.
Published: May 2010

Daily financial returns (and daily stock returns, in particular) are commonly modeled as GARCH(1, 1) processes. Here we test this specification using new model evaluation technology developed by Ashley and Patterson that examines the ability of the estimated model to reproduce features of particular interest: various aspects of nonlinear serial dependence, in the present instance. Using daily returns to the CRSP equally weighted stock index, we find that the GARCH(1, 1) specification cannot be rejected; thus, this model appears to be reasonably adequate in terms of reproducing the kinds of nonlinear serial dependence addressed by the battery of nonlinearity tests used here.