bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification of pharmaceutical preparations using thin‐layer chromatography to obtain mass spectra with Direct Analysis in Real Time and accurate mass spectrometry
Authors: Wood Jessica L. , Steiner Robert R.
Published: May 2011

Forensic analysis of pharmaceutical preparations requires a comparative analysis with a standard of the suspected drug in order to identify the active ingredient. Purchasing analytical standards can be expensive or unattainable from the drug manufacturers. Direct Analysis in Real Time (DART™) is a novel, ambient ionization technique, typically coupled with a JEOL AccuTOF™ (accurate mass) mass spectrometer. While a fast and easy technique to perform, a drawback of using DART™ is the lack of component separation of mixtures prior to ionization. Various in‐house pharmaceutical preparations were purified using thin‐layer chromatography (TLC) and mass spectra were subsequently obtained using the AccuTOF™‐ DART™ technique. Utilizing TLC prior to sample introduction provides a simple, low‐cost solution to acquiring mass spectra of the purified preparation. Each spectrum was compared against an in‐house molecular formula list to confirm the accurate mass elemental compositions. Spectra of purified ingredients of known pharmaceuticals were added to an in‐house library for use as comparators for casework samples. Resolving isomers from one another can be accomplished using collision‐induced dissociation after ionization. Challenges arose when the pharmaceutical preparation required an optimized TLC solvent to achieve proper separation and purity of the standard. Purified spectra were obtained for 91 preparations and included in an in‐house drug standard library. Primary standards would only need to be purchased when pharmaceutical preparations not previously encountered are submitted for comparative analysis. TLC prior to DART™ analysis demonstrates a time efficient and cost saving technique for the forensic drug analysis community. Copyright © 2011 John Wiley & Sons, Ltd.
Zebrafish heat shock protein a4 genes in the intestinal epithelium are up‐regulated during inflammation
Authors: Crawford Katie C. , Vega Flores Maria , Oehlers Stefan H. , Hall Christopher J. , Crosier Kathryn E. , Crosier Philip S.
Published: May 2011

A number of heat shock proteins (HSPs), including Hsp70 and Hsp110, function as molecular chaperones within intestinal epithelial cells that line the mammalian digestive system. HSPs confer cellular protection against environmental stress induced by chemical toxins or pathogens. There is interest in how members of this protein family might influence the progression of inflammatory bowel disease. Using the zebrafish model system, we report the expression of the duplicated hspa4 genes within the intestinal epithelium. The hspa4 genes belong to the Hsp110 family. We show that under inflammatory stress conditions within the gut, expression of these genes is up‐regulated in a similar manner to that previously observed for mammalian Hsp70. Because of the amenability of the zebrafish to whole‐animal screening protocols, the hspa4 genes could be used as effective read‐outs for genetic, chemical and environmental factors that might influence intestinal inflammation. genesis 49:905–911, 2011. © 2011 Wiley Periodicals, Inc.
Syntheses, Crystal Structures, and Optical Properties of Indium Arsenic(III) Oxide Halides: In2(As2O5)Cl2 and In4(As2O5)(As3O7)Br3
Authors: Jiang Xiao‐Ming , Xu Zhong‐Ning , Zhao Zhong‐Yan , Guo Sheng‐Ping , Guo Guo‐Cong , Huang Jin‐Shun
Published: May 2011

Two new indium arsenic(III) oxide halides, In2(As2O5)Cl2 (1) and In4(As2O5)(As3O7)Br3 (2), have been prepared by solid‐state reaction. Both of the compounds feature layered structures, in which indium–oxide halide octahedral rings or indium–oxo chains are bridged by indium–oxide halide octahedral dimers or indium–oxo unicapped trigonal prisms, and the interlinkage between the rings or chains is also consolidated by (As2O5)4– anions for 1, or (As2O5)4– and (As3O7)5– anions for 2. Compound 2 is the first compound in which three different indium‐ion coordination geometries coexist with the In3+ cations coordinated by O2– and Br– to form [InO6], [InO7], and [InOBr3] units. The diffuse reflectance spectra and band‐structure calculations show that they are wide‐band‐gap semiconductors.
[2+2] Photocycloaddition of Symmetrically Disubstituted Alkenes to 2(5H)‐Furanones: Diastereoselective Entry to 1,2,3,4‐Tetrasubstituted Cyclobutanes
Authors: Parés Sònia , de March Pedro , Font Josep , Alibés Ramon , Figueredo Marta
Published: May 2011

A study on the [2+2] photochemical cycloaddition of 1,4‐difunctionalized 2‐butenes to 2(5H)‐furanones is presented. These reactions deliver 1,2,3,4‐tetrasubstituted cyclobutanes with suitable functionalization in the four side chains for further synthetic elaboration. The effects of the substituents in both the lactone and the 2‐butene on the stereoselectivity of the photochemical reaction have been evaluated. Starting from (Z)‐2‐butenes, under photosensitized conditions, a competitive cis/trans isomerization of the olefin inhibits the cycloaddition process. It was found that the presence of a cis double bond confined within a medium‐size ring does not prevent bond rotation in the intermediate 1,4‐biradicals.
Combination of hydrodynamic cavitation and chlorine dioxide for disinfection of water
Authors: Maslak Dominik , Weuster‐Botz Dirk
Published: May 2011

The combination of hydrodynamically generated cavitation with disinfectants is a new approach for disinfection of water. The aim of this study was to investigate the inactivation of Escherichia coli at high cell densities (∼107 cells mL–1) with a combination of hydrodynamic cavitation and chlorine dioxide. A new type of hydrodynamic cavitation reactor (micro wire mesh with downstream nozzle) was developed, which consumes 30% less energy than conventionally used orifice plates at similar flow rates. Compared with sole chlorine dioxide incubation the combination of chlorine dioxide with hydrodynamically generated cavitation resulted in a reduction of 50–70% of incubation time for 99% cell inactivation at an initial chlorine dioxide concentration of 0.25 mg L–1. The final viable cell number was reduced by a factor of 100–1000 compared to sole chlorine dioxide disinfection. An energy demand of ∼0.1–0.2 kWh m–1 is necessary to induce hydrodynamic cavitation at these optimum operation conditions (cavitation number of 0.13–0.17). Higher inactivation rates, the reduction of surviving cells by orders of magnitude compared to sole chlorine dioxide inactivation or the reduction of initial chlorine dioxide concentration compensate for the additional energy demand.
Fully automated production of potential Malaria vaccines with Pichia pastoris in integrated processing
Authors: Martens Sanja , Borchert Sven‐Oliver , Faber Bart W. , Cornelissen Gesine , Luttmann Reiner
Published: May 2011

Here, we have studied the setup of an integrated bioprocess for the production of artificial Malaria vaccine candidates with Pichia pastoris. Production of pharmaceutically relevant proteins such as vaccines has high demands regarding protein processing in the bioreactor and for subsequent purification. To implement this challenging protein expression process, a highly instrumented bioreactor was configured for repeated fed batch cultivations and supplemented with an at‐line monitoring of the target protein production via HPLC. The integration of a fast in situ purification of the sensitive products using an expanded bed adsorption for a sequential integrated bioprocess allows cyclic product separation. Thus, a fully automated production of artificial malaria vaccines was achieved.
Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice
Authors: Falk Marni J. , Polyak Erzsebet , Zhang Zhe , Peng Min , King Rhonda , Maltzman Jonathan S. , Okwuego Ezinne , Horyn Oksana , Nakamaru‐Ogiso Eiko , Ostrovsky Julian , Xie Letian X. , Chen Jia Yan , Marbois Beth , Nissim Itzhak , Clarke Catherine F. , Gasser David L.
Published: May 2011

Therapy of mitochondrial respiratory chain diseases is complicated by limited understanding of cellular mechanisms that cause the widely variable clinical findings. Here, we show that focal segmental glomerulopathy‐like kidney disease in Pdss2 mutant animals with primary coenzyme Q (CoQ) deficiency is significantly ameliorated by oral treatment with probucol (1% w/w). Preventative effects in missense mutant mice are similar whether fed probucol from weaning or for 3 weeks prior to typical nephritis onset. Furthermore, treating symptomatic animals for 2 weeks with probucol significantly reduces albuminuria. Probucol has a more pronounced health benefit than high‐dose CoQ10 supplementation and uniquely restores CoQ9 content in mutant kidney. Probucol substantially mitigates transcriptional alterations across many intermediary metabolic domains, including peroxisome proliferator‐activated receptor (PPAR) pathway signaling. Probucol's beneficial effects on the renal and metabolic manifestations of Pdss2 disease occur despite modest induction of oxidant stress and appear independent of its hypolipidemic effects. Rather, decreased CoQ9 content and altered PPAR pathway signaling appear, respectively, to orchestrate the glomerular and global metabolic consequences of primary CoQ deficiency, which are both preventable and treatable with oral probucol therapy.
Development and Fabrication of a New Concept Planar‐tubular Solid Oxide Fuel Cell (PT‐SOFC)
Authors: Chen Y. , Chen F. , Ding D. , Gao J.
Published: May 2011

The paper reports a new concept of planar‐tubular solid oxide fuel cell (PT‐SOFC). Emphasis is on the fabrication of the required complex configuration of Ni‐yttria‐stabilised zirconia (YSZ) porous anode support by tert‐butyl alcohol (TBA) based gelcasting, particularly the effects of solid loading, amounts of monomers and dispersant on the rheological behaviour of suspension, the shrinkage of a wet gelcast green body upon drying, and the properties of final sample after sintering at 1350 °C and reduction from NiO‐YSZ to Ni‐YSZ. The results show that the gelcasting is a powerful method for preparation of the required complex configuration anode support. The anode support resulted from an optimised suspension with the solid loading of 25 vol% has uniform microstructure with 37% porosity, bending strength of 44 MPa and conductivity of 300 S cm—1 at 700 °C, meeting the requirements for an anode support of SOFC. Based on the as‐prepared anode support, PT‐SOFC single cell of Ni‐YSZ/YSZ/LSCF has been fabricated by slurry coating and co‐sintering technique. The cell peak power density reaches 63, 106 and 141 mW cm—2 at 700, 750 and 800 °C, respectively, using hydrogen as fuel and ambient air as oxidant.
Microtubule assembly affects bone mass by regulating both osteoblast and osteoclast functions: Stathmin deficiency produces an osteopenic phenotype in mice
Authors: Liu Hongbin , Zhang Rongrong , Ko Seon-Yle , Oyajobi Babatunde O , Papasian Christopher J , Deng Hong-Wen , Zhang Shujun , Zhao Ming
Published: May 2011

Cytoskeleton microtubules regulate various cell signaling pathways that are involved in bone cell function. We recently reported that inhibition of microtubule assembly by microtubule-targeting drugs stimulates osteoblast differentiation and bone formation. To further elucidate the role of microtubules in bone homeostasis, we characterized the skeletal phenotype of mice null for stathmin, an endogenous protein that inhibits microtubule assembly. In vivo micro–computed tomography (µCT) and histology revealed that stathmin deficiency results in a significant reduction of bone mass in adult mice concurrent with decreased osteoblast and increased osteoclast numbers in bone tissues. Phenotypic analyses of primary calvarial cells and bone marrow cells showed that stathmin deficiency inhibited osteoblast differentiation and induced osteoclast formation. In vitro overexpression studies showed that increased stathmin levels enhanced osteogenic differentiation of preosteoblast MC3T3-E1 cells and mouse bone marrow–derived cells and attenuated osteoclast formation from osteoclast precursor Raw264.7 cells and bone marrow cells. Results of immunofluorescent studies indicated that overexpression of stathmin disrupted radial microtubule filaments, whereas deficiency of stathmin stabilized the microtubule network structure in these bone cells. In addition, microtubule-targeting drugs that inhibit microtubule assembly and induce osteoblast differentiation lost these effects in the absence of stathmin. Collectively, these results suggest that stathmin, which alters microtubule dynamics, plays an essential role in maintenance of postnatal bone mass by regulating both osteoblast and osteoclast functions in bone. © 2011 American Society for Bone and Mineral Research
Cross‐talk between cell cycle induction and mitochondrial dysfunction during oxidative stress and nerve growth factor withdrawal in differentiated PC12 cells
Authors: Bianco Maria Rosaria , Berbenni Miluscia , Amara Flavio , Viggiani Sandra , Fragni Martina , Galimberti Valentina , Colombo Daniele , Cirillo Giovanni , Papa Michele , Alberghina Lilia , Colangelo Anna Maria
Published: May 2011

Neuronal death has been reported to involve mitochondrial dysfunction and cell cycle reentry. In this report, we used Nerve Growth Factor (NGF)‐differentiated PC12 cells to investigate mechanisms linking mitochondrial dysfunction and cell cycle activation during neuronal death induced by NGF withdrawal and/or oxidative stress. We found that loss of survival following H2O2‐induced oxidative stress or NGF deprivation was preceded by a decrease in mitochondrial membrane potential (ΔΨm), increase in reactive oxygen species (ROS), and up‐regulation of cyclin D1 and phosphorylation (Ser‐780) of protein retinoblastoma (P‐pRb), without an increase of proliferation rates. Treatment with H2O2, but not NGF deprivation, also induced the phosporylation (Ser‐10) of p27kip1 and the appearance of a cleaved P‐p27kip1 fragment of about 15 kDa. The extent of cell cycle activation appeared to be inversely correlated to the duration of toxic stimuli (pulse/continuous). H2O2‐induced mitogenic responses appeared to be mediated by induction of P‐MAPK and P‐Akt and were blocked by p38MAPK and JNK inhibitors as well as by the CDK inhibitor flavopiridol (Flav) and by sodium selenite (Sel), a component of selenoproteins, including glutathione peroxidases. Inhibition of p38MAPK and JNK, instead, did not affect cyclin D1 changes following NGF deprivation. Finally, both Flav hydrochloride and Sel partially prevented mitochondrial dysfunction and cell death following NGF withdrawal or H2O2 toxicity, but not during oxidative stress in the absence of NGF. Taken together, these data suggest that H2O2‐induced oxidative stress can determine distinct patterns of mitogenic responses as a function of mitochondrial dysfunction depending on 1) intensity/duration of stress stimuli and/or 2) presence of NGF. © 2011 Wiley‐Liss, Inc.
Single and local blockade of interleukin‐6 signaling promotes neuronal differentiation from transplanted embryonic stem cell‐derived neural precursor cells
Authors: Gomi Masanori , Aoki Tomohiro , Takagi Yasushi , Nishimura Masaki , Ohsugi Yoshiyuki , Mihara Masahiko , Nozaki Kazuhiko , Hashimoto Nobuo , Miyamoto Susumu , Takahashi Jun
Published: May 2011

Safe and efficient transplantation of embryonic stem (ES) cells to the brain requires that local inflammatory and immune responses to allogeneic grafts are inhibited. To investigate cytokines that affect graft cell survival and differentiation, we used stromal cell‐derived inducing activity to induce the differentiation of neural progenitor cells (NPCs) from mouse ES cells and transplanted the NPCs into mouse brain. Examination of surrounding brain tissue revealed elevated expression levels of interleukin (IL)‐1β, IL‐4, and IL‐6 in response to NPC transplantation. Among these, only IL‐6 reduced neuronal differentiation and promoted glial differentiation in vitro. When we added anti‐IL‐6 receptor antibodies to NPCs during transplantation, this single and local blockade of IL‐6 signaling reduced the accumulation of host‐derived leukocytes, including microglia. Furthermore, it also promoted neuronal differentiation and reduced glial differentiation from the grafted NPCs to an extent similar to that with systemic and continuous administration of cyclosporine A. These results suggest that local administration of anti‐IL‐6 receptor antibodies with NPCs may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy. © 2011 Wiley‐Liss, Inc.
Local establishment of repetitive long‐term potentiation‐induced synaptic enhancement in cultured hippocampal slices with divided input pathways
Authors: Oe Yuki , Tominaga‐Yoshino Keiko , Ogura Akihiko
Published: May 2011

Long‐term potentiation (LTP) in the rodent hippocampus is a popular model for synaptic plasticity, which is considered the cellular basis for brain memory. Because most LTP analysis involves acutely prepared brain slices, however, the longevity of single LTP has not been well documented. Using stable hippocampal slice cultures for long‐term examination, we previously found that single LTP disappeared within 1 day. In contrast, repeated induction of LTP led to the development of a distinct type of plasticity that lasted for more than 3 weeks and was accompanied by the formation of new synapses. Naming this novel plastic phenomenon repetitive LTP‐induced synaptic enhancement (RISE), we proposed it as a model for the cellular processes involved in long‐term memory formation. However, because in those experiments LTP was induced pharmacologically in the whole slice, it is not known whether RISE has input‐pathway specificity, an essential property for memory. In this study, we divided the input pathway of CA1 pyramidal neurons by a knife cut and induced LTP three times, the third by tetanic stimulation in one of the divided pathways to express RISE specifically. Voltage‐sensitive dye imaging andGolgi‐staining performed 2 weeks after the three LTP inductions revealed both enhanced synaptic strength and increased dendritic spine density confined to the tetanized region. These results demonstrate that RISE is a feasible cellular model for long‐term memory. © 2011 Wiley‐Liss, Inc.
Does dynamical downscaling introduce novel information in climate model simulations of precipitation change over a complex topography region?
Authors: Tselioudis George , Douvis Costas , Zerefos Christos
Published: May 2011

Current climate and future climate‐warming runs with the RegCM Regional Climate Model (RCM) at 50 and 11 km‐resolutions forced by the ECHAM GCM are used to examine whether the increased resolution of the RCM introduces novel information in the precipitation field when the models are run for the mountainous region of the Hellenic peninsula. The model results are inter‐compared with the resolution of the RCM output degraded to match that of the GCM, and it is found that in both the present and future climate runs the regional models produce more precipitation than the forcing GCM. At the same time, the RCM runs produce increases in precipitation with climate warming even though they are forced with a GCM that shows no precipitation change in the region. The additional precipitation is mostly concentrated over the mountain ranges, where orographic precipitation formation is expected to be a dominant mechanism. It is found that, when examined at the same resolution, the elevation heights of the GCM are lower than those of the averaged RCM in the areas of the main mountain ranges. It is also found that the majority of the difference in precipitation between the RCM and the GCM can be explained by their difference in topographic height. The study results indicate that, in complex topography regions, GCM predictions of precipitation change with climate warming may be dry biased due to the GCM smoothing of the regional topography. Copyright © 2011 Royal Meteorological Society
ACL reconstruction using bone‐tendon‐bone graft engineered from the semitendinosus tendon by injection of recombinant BMP‐2 in a rabbit model
Authors: Hashimoto Yusuke , Naka Yoshifumi , Fukunaga Kenji , Nakamura Hiroaki , Takaoka Kunio
Published: May 2011

We attempted to generate a bone‐tendon‐bone structure by injecting human‐type recombinant human bone morphogenetic protein‐2 (rhBMP‐2) into the semitendinosus tendon, and an anterior cruciate ligament (ACL) defect was reconstructed by grafting the engineered bone‐tendon‐bone graft. Two ossicles with a separation distance of 1 cm were generated within the left semitendinosus tendon of a rabbit 6 weeks after the injection of rhBMP‐2 (15 µg at each site). The engineered bone‐tendon‐bone graft was transplanted in order to reconstruct the ACL by passing the graft through the bone tunnels. In the control group, the ACL was reconstructed with the semitendinosus tendon without BMP‐2 using the same methods as those used in the experimental group. The animals were harvested at 4 or 8 weeks after surgery and examined by radiographic, histological, and biomechanical methods. In the experimental group, ossicles in the bone‐tendon‐bone graft were successfully integrated into the host bone of the femur and tibia. Histological analysis revealed that characteristic features identical to the normal direct insertion morphology had been restored. Biomechanical pull‐out testing showed that the ultimate failure load and stiffness of the reconstructed ACL in the experimental group were significantly higher than those in the control group at both 4 and 8 weeks (p < 0.05). These results indicate the potential of regenerative reconstruction of the ACL, and the reconstruction resulted in the restoration of morphology and function equivalent to those of the normal ACL. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1923–1930, 2011
Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobalt–chromium–molybdenum (CoCrMo) particles‐induced tumor necrosis factor‐α (TNFα) secretion in MLO‐Y4 osteocytes
Authors: Orhue Vbenosawemwinghaye , Kanaji Arihiko , Caicedo Marco S. , Virdi Amarjit S. , Sumner Dale R. , Hallab Nadim J. , Jahr Holger , Sena Kotaro
Published: May 2011

Aseptic loosening is the devastating long term complication of total hip arthroplasty and orthopedic implant debris has been shown to trigger an intense inflammatory reaction leading to resorption of the bone matrix. Inflammatory cytokines, such as tumor necrosis factor‐α (TNFα), have been implicated in this process and osteocytes may play a role in its production. We previously demonstrated that cobalt–chromium–molybdenum (CoCrMo) particles upregulate TNFα production by MLO‐Y4 osteocytes in vitro, but the underlying mechanism has not been elucidated. Based on previous studies by others, we hypothesized that the calcineurin‐nuclear factor of activated T cells (NFAT) pathway mediates CoCrMo particle‐induced TNFα production in MLO‐Y4 osteocytes. MLO‐Y4 osteocytes exposed to CoCrMo particle treatment resulted in a rapid and significant increase in calcineurin activity. We also demonstrate that CoCrMo particle‐induced upregulation of TNFα is reduced to control levels with calcineurin‐NFAT inhibitors and this was also confirmed at mRNA level. Moreover, we demonstrate the localization of NFATs in MLO‐Y4 osteocytes and that NFAT1 and 2 translocate to the nucleus upon CoCrMo particle treatment. Our results suggest that calcineurin‐NFAT signaling is involved in TNFα production by MLO‐Y4 osteocytes after CoCrMo particle treatment. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1867–1873, 2011
Preparative purification of gentamicin components using high‐speed counter‐current chromatography coupled with electrospray mass spectrometry
Authors: Inoue Koichi , Hattori Yasuko , Horie Masakazu , Tomoaki Hino  , Oka Hisao
Published: May 2011

We developed a useful and preparative method based on high‐speed counter‐current chromatography with mass spectrometry (HSCCC/MS) to purify gentamicin C1a, C2/2a and C1 from standard powder. The analytes were purified on the HSCCC model CCC‐1000 (multi‐layer coil planet centrifuge) with a volatile two‐phase solvent system composed of n‐butanol/10% aqueous ammonia solution (50:50, v/v) and detected on an LCMS‐2020EV quadrupole mass spectrometer fitted with an electrospray ionization (ESI) source system in positive ionization following scan mode (m/z 100–500). The HSCCC/ESI‐MS peaks indicated that gentamicin C1a (m/z 450: [M+H]+), C2/2a (m/z 464: [M+H]+) and C1 (m/z 478: [M+H]+) have the peak resolution values of 1.3 and 1.7 from 30 mg of loaded gentamicin powder. The HSCCC yielded 3.9 mg of gentamicin C1a, 12.6 mg of gentamicin C2/2a and 12.0 mg of gentamicin C1. These purified substances were analyzed by LC/MS with scan positive‐mode. Based on the LC/MS chromatograms and spectra of the fractions, analytes were estimated to be over 95% pure. These gentamicin isomers of C1a, C2/2a and C1 were evaluated for their antibacterial activities. The overall results indicate that this approach of HSCCC/MS is a powerful technique for the purification of gentamicin components.
A new method that uses cyanoacrylate tissue adhesive to fill scoring incisions in septal cartilage correction
Authors: Özyazgan İrfan , İdacı Onurkan
Published: May 2011

Objectives/Hypothesis:

Numerous methods are used in the correction of deviated septal cartilage. One of these methods is to perform partial‐thickness incisions (scoring) on the concave side of the deviated cartilage. In this retrospective report, we present a series of patients who were treated by filling the scoring incision gaps with cyanoacrylate‐based tissue adhesives to increase the effectiveness of scoring incisions and to maintain stability of the corrected concave cartilage segments.

Study Design:

A retrospective clinical study presenting a patient group who was treated using a new surgical method for septal deviation.

Methods:

Twenty‐three patients with septum deviation and nasal deformity underwent surgery with the open rhinoplasty approach. Intra‐ or extracorporeal scoring incisions were performed on the concave side of the deviated septal cartilage, and cyanoacrylate tissue adhesives were applied to the incisions of the corrected cartilage. After polymerization and hardening of the cyanoacrylate tissue adhesive, the operation continued in the normal manner. Preoperative and postoperative clinical results and computed tomography images of the patients were assessed.

Results:

With a mean 24‐month follow‐up, all patients with respiratory complaints related to deviated septum reported improvement in nose breathing. Clinical and radiologic observations showed that the corrected septum was stable in its new position. There were no complications arising from the use of cyanoacrylate.

Conclusions:

Cyanoacrylate is an effective, instant, safe method of treatment in correcting deviated septal cartilage with scoring incisions and filling the gaps of the incisions.
Genetic characteristics in children with cochlear implants and the corresponding auditory performance
Authors: Wu Chen‐Chi , Liu Tien‐Chen , Wang Shih‐Hao , Hsu Chuan‐Jen , Wu Che‐Ming
Published: May 2011

Objectives/Hypothesis:

To explore the genetic characteristics of children with cochlear implants (CIs) and to correlate the auditory performance after implantation to the genetic diagnosis of children with CIs.

Study Design:

Prospective cohort study.

Methods:

Mutations of four common deafness‐associated genes, GJB2, SLC26A4, the mitochondrial 12S rRNA gene, and OTOF, were screened in 743 unrelated children with idiopathic sensorineural hearing impairment, including 180 and 563 children with and without CIs, respectively. The allele frequencies and audiologic features were compared between both groups. The Categories of Auditory Performance (CAP) scores at 3 years after implantation were then analyzed according to the genotypes.

Results:

A definitive genetic diagnosis was made in 37 (20.6%) of the 180 CI children. A significant difference in allele frequencies between CI and non‐CI children was found in GJB2 mutations (chi‐square test, P < .01), but not in SLC26A4 mutations, mitochondrial 12S rRNA mutations, or OTOF mutations (all P > .05). Further analysis revealed that the difference might have resulted from distinct audiological features in each group. Among the 110 CI children who had received more than 3 years of rehabilitation after implantation, the 35 children with mutations had better CAP scores than the 75 children without mutations.

Conclusions:

A significant prevalence of genetic mutations was identified in children with CIs, suggesting the need for routine genetic assessments. The frequencies of common deafness‐associated mutations were different between children with and without CIs. The presence of genetic mutations was associated with an excellent long‐term auditory performance outcome after implantation.
Validation of edible taste strips for identifying PROP taste recognition thresholds
Authors: Desai Hetvi , Smutzer Gregory , Coldwell Susan E. , Griffith James W.
Published: May 2011

Objectives/Hypothesis:

The purpose of this study was to validate the use of edible taste strips for measuring taste recognition thresholds for the bitter‐tasting compound 6‐n‐propylthiouracil (PROP).

Study Design:

Taste recognition thresholds for PROP were obtained by two separate methods. Thresholds were also identified in subjects whose airflow through the nose was blocked. Threshold values were then compared to genotype analysis of the TAS2R38 taste receptor, which is the major determinant for the detection of PROP.

Methods:

Edible taste strips were used to examine taste recognition thresholds for PROP. Thresholds were determined by the method of ascending limits and by the method of reversals. Single nucleotide polymorphism analysis of the TAS2R38 gene was used to identify PROP taster status.

Results:

Taste recognition thresholds for PROP formed two distributions. Thresholds for one group varied from 4 to 219 nmol and represented PROP tasters. The second group could not detect the bitter taste of PROP at ≤800 nmol and represented PROP nontasters. The method of ascending limits and the method of reversals yielded similar threshold results. The expression of a PAV allele permitted detection of PROP, but AVI homozygotes could not detect the bitter taste of PROP.

Conclusions:

Edible taste strips were successfully used to detect PROP thresholds at values equal to or lower than those obtained in previous studies using PROP solutions or PROP‐impregnated filter papers. This study provides validity evidence for the use of edible taste strips for identifying PROP in the human population.
The grainyhead‐like 2 gene (GRHL2) single nucleotide polymorphism is not associated with age‐related hearing impairment in Han Chinese
Authors: Lin Yan‐Han , Wu Chen‐Chi , Hsu Chuan‐Jen , Hwang Juen‐Haur , Liu Tien‐Chen
Published: May 2011

Objectives/Hypothesis:

The grainyhead‐like 2 gene (GRHL2) was found to be associated with age‐related hearing impairment (ARHI) in Europeans. We tested whether the same association exists in the Han Chinese population.

Study Design:

Individual cohort study.

Methods:

Among a total of 1,175 Han Chinese volunteers, 310 were classified into the case group (the 26% with poorest hearing), and 308 were placed into the control group (the 26% with best hearing) according to the Zhigh scores converted from the original frequency‐specific hearing thresholds. The GRHL2 single nucleotide polymorphism locus (rs10955255: A/G) in intron 1 (coordinate: 102605581) shown in the HapMap was genotyped with correlation to the audiologic phenotypes.

Results:

The genotype distributions of GRHL2 (AA/AG/GG) were not significantly different between the control and the case groups (P = .349). Compared to genotype AA, the odds ratios of the GRHL2 genotypes AG and GG for ARHI were not significantly different after adjustment for other environmental risk factors by logistic regression analyses; 0.78 ± 0.139, 95% confidence interval (CI) = 0.55 ∼ 1.10, P = .160 for AG; 0.85 ± 0.283, 95% CI = 0.44 ∼ 1.63, P = .625 for GG. In each audiogram pattern, AA was most common, but the adjusted odds ratios of the genotypes AG and GG for ARHI still were not significantly different.

Conclusions:

Our results showed no positive association between GRHL2 polymorphisms and ARHI in Han Chinese individuals. Population differences might be a key factor leading to nonreplication of the association.
Radiofrequency tissue volume reduction for treatment of auricle keloids
Authors: Fruth Kai , Gouveris Haralampos , Kuelkens Christoph , Mann Wolf J.
Published: May 2011

Objectives/Hypothesis:

Keloids are often refractive to treatment, and recurrences occur quite frequently. Radiofrequency tissue volume reduction (RFTVR) is a surgical technology that induces extensive fibrosis at the target tissues.

Methods:

We applied RFTVR in 14 patients (19 auricles, 5 patients treated bilaterally; 9 female, 5 male; range, 10–66 years) with keloids of the auricle. Keloids were located at the earlobe in 4 patients (5 auricles), helix in 9 patients (12 auricles), and at both earlobe and helix in 1 patient (2 auricles). In 6 patients (8 auricles) RFTVR was the sole treatment modality applied, and in 7 patients (10 auricles) intralesional steroid injection was also performed. Patients underwent one to seven sessions of RFTVR. Patients were followed up between 2 and 92 months postoperatively (median, 24.5 months).

Results:

Good cosmetic results were achieved in 10 of 14 patients (13 auricles). Three patients (5 auricles) were refractive to treatment, and 1 patient (1 auricle) showed progressive disease despite treatment.

Conclusions:

Radiofrequency tissue volume reduction may be considered as a new, minimally invasive treatment option for keloids of the auricle.
Contemporary management of acoustic neuromas
Authors: Theodosopoulos Philip V. , Pensak Myles L.
Published: May 2011

Objectives/Hypothesis:

This review of the literature on vestibular schwannomas focuses on the developments in the fields of surgery, radiosurgery, and observation during the past decade that have redefined the treatment algorithm. The authors hope to derive some recommendations that are evidence based and applicable to everyday clinical practice while advancing the dialogue regarding the optimal management of these lesions.

Study Design:

Contemporary review.

Methods:

English literature search for acoustic neuroma or vestibular schwannoma.

Results:

Radiosurgical treatment appears to maintain strong tumor control during an ever‐increasing number of years of follow‐up. Fractionated radiation therapy, with attention to limiting the cochlear radiation dose, seems to afford the best hearing‐nerve functional outcomes. Microsurgical treatment remains the best cytoreductive therapy, and although it cannot achieve the facial and hearing nerve outcomes of radiosurgery, it is still the preferred treatment for large lesions causing mass effect and obstructive hydrocephalus. Bevacizumab holds substantial promise for the treatment of neurofibromatosis type 2–associated progressive lesions.

Conclusions:

Our review of the literature suggests that near‐total or extensive subtotal resection of vestibular schwannomas may confer much improved functional outcomes without significant detriment to acceptable rates of tumor control. However, further follow‐up is needed in patients treated with this relatively novel surgical paradigm.
DNA Amplification via Polymerase Chain Reaction Inside Miniemulsion Droplets with Subsequent Poly(n‐butylcyanoacrylate) Shell Formation and Delivery of Polymeric Capsules into Mammalian Cells
Authors: Baier Grit , Musyanovych Anna , Landfester Katharina , Best Andreas , Lorenz Steffen , Mailänder Volker
Published: May 2011

There is a growing interest in the development of stable nanocapsules that could deliver the bioactive compounds within the living organism, and to release them without causing any toxic effects. Here the miniemulsion droplets were first used as “nanoreactors” for the amplification of single‐molecule dsDNA template (476 and 790 base pairs) through PCR. Afterwards, each droplet was surrounded with a biodegradable PBCA shell by interfacial anionic polymerization, enabling therefore to deliver the PCR products into the cells. The size of the initial miniemulsion droplets and the final polymeric capsules was in the range of 250 and 320 nm, mainly depending on the type of the continuous phase and presence of dsDNA template molecules. The formation of PCR products was resolved with gel electrophoresis and detected with fluorescence spectroscopy in the presence of DNA specific dye (SYBRGreen). TEM studies were performed to prove the formation of the polymeric shell. The shell thickness was measured to be within 5–15 nm and the average molecular weight of the formed PBCA polymer was around 75000 g · mol−1. For the cell uptake experiments, the obtained nanocapsules were transferred from the organic phase into aqueous medium containing a water‐soluble surfactant. The effect of the surfactant type (anionic, cationic or non‐ionic) on the HeLa cell viability and nanocapsule uptake behavior was studied by CLSM and FACS. Confocal analysis demonstrated that nanocapsules stabilized with cationic (CTMA‐Cl) and non‐ionic (Lutensol AT50) surfactants show almost the same uptake, whereas capsules redispersed in anionic (SDS) surfactant possess a 30% higher uptake. The release of the encapsulated material within the cell was studied on the example of Cy5‐labeled oligonucleotides showing the colocalization with mitochondria of MSCs cells.

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Biofunctionalization of Polyelectrolyte Microcapsules with Biotinylated Polyethylene Glycol‐Grafted Liposomes
Authors: Gao Jie , Reibetanz Uta , Venkatraman Subbu , Neu Björn
Published: May 2011

Hollow polyelectrolyte microcapsules (PEMC) are prepared using layer‐by‐layer self‐assembly of polyelectrolytes on melamine formaldehyde templates, followed by template dissolution, and subsequent coating with biotinylated polyethylene glycol‐grafted liposomes. These potential site‐specific carrier systems show a high specificity for NeutrAvidin binding and a strong resistance against unspecific protein binding. It is concluded that this design with NeutrAvidin as the outermost layer of such capsules provides an ideal platform for the biofunctionalization of PEMC as drug delivery systems or as artificial cell‐like structures for biomimetic studies.

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The nuclear receptor constitutive active/androstane receptor arrests DNA‐damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase
Authors: Kamino Hiroki , Negishi Masahiko
Published: May 2011

Here, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA‐damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over‐expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4‐bis[2‐(3,5‐dichloropyridyloxy)]benzene; androstenol, 16,(5α)‐androsten‐3α‐OL), or repressor androstenol; these treatments were then followed by adriamycin treatment to damage DNA. FACS analysis revealed that CAR‐activation by TCPOBOP increased the rate of arrested Huh7 cells at the G2/M phase (4N DNA content) after DNA damage by adriamycin. This increase correlated with the increase of cell viability in TCPOBOP‐treated Huh7 cells, as determined by MTT assays. Real‐time polymerase chain reaction analysis determined that, as regulated by CAR, the growth arrest and DNA damage‐inducible γ (GADD45γ) and Cyclin G2 genes increased and decreased, respectively, as TCPOBOP increased the number of Huh7 cells arrested at the G2/M phase. Thus, the results suggest that CAR regulates cell cycle, increasing G2/M arrest, and delaying the death of DNA‐damaged cells. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.
Oroxylin a reverses multi‐drug resistance of human hepatoma BEL7402/5‐FU cells via downregulation of P‐glycoprotein expression by inhibiting NF‐κB signaling pathway
Authors: Yang Hui‐Ying , Zhao Li , Yang Zhen , Zhao Qing , Qiang Lei , Ha Jun , Li Zhi‐Yu , You Qi‐Dong , Guo Qing‐Long
Published: May 2011

In this study, oroxylin A showed strong reversal potency in BEL7402/5‐FU cells and the reversal fold (RF) reached 4.69. Simultaneously, rhodamine‐123 accumulation assay and flow cytometry analysis demonstrated oroxylin A could increase drug accumulation. When combined with oroxylin A, 5‐FU showed inducing apoptosis effect more seriously in DAPI staining experiment. Moreover, the mRNA and protein expression of multi‐drug resistance gene (MDR1) were also decreased by oroxylin A. Further experiments exhibited that oroxylin A can downregulate P‐gp expression through inhibiting nuclear factor‐κB (NF‐κB) signaling pathway, which might be the mechanism of reversal resistance of oroxylin A. In summary, oroxylin A could be a good candidate for the development of new MDR reversal agent and its reversal mechanism probably due to the suppression of P‐gp expression via inhibiting NF‐κB signaling pathway. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.
Urinary polyphenols, glutathione S‐transferases copy number variation, and breast cancer risk: Results from the Shanghai women's health study
Authors: Luo Jianfeng , Gao Yu‐Tang , Chow Wong‐Ho , Shu Xiao‐ou , Li Honglan , Yang Gong , Cai Qiuyin , Li Guoliang , Rothman Nathaniel , Cai Hui , Shrubsole Martha J. , Franke Adrian A. , Zheng Wei , Dai Qi
Published: May 2011

In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione S‐transferases (GSTs), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk. We conducted a study of 352 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40–70 yr at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real‐time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes. Urinary excretion of flavonols and flavanols, particularly EGC (P = 0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a P‐value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol. The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.
Crosswind thresholds supporting wake‐vortex‐free corridors for departing aircraft
Authors: Dengler K. , Holzäpfel F. , Gerz T. , Wiegele A. , De Visscher I. , Winckelmans G. , Bricteux L. , Fischer H. , Konopka J.
Published: May 2011

During two field measurement campaigns aircraft wake vortex trajectory and wind measurement data have been collected at Frankfurt airport. Three different approaches have been used to analyse the data in order to estimate crosswind threshold values supporting vortex‐free corridors for departing aircraft. Although several competing effects such as wake vortex transport in and out of ground effect, temporal and spatial wind variability, and the spreading of aircraft trajectories after take‐off, complicate the analyses, all three approaches lead to similar crosswind thresholds. Employing standard instrumentation at 10 m, a minimum crosswind threshold of 3.5–4.6 m s−1 has been identified to clear a safety corridor of 150 m width from wake vortices with a 95% probability within 60 s. Alternative estimations of crosswind thresholds employing different instrumentation and different height ranges are reported. Crosswind thresholds can be reduced if the wind is measured close to the air mass in which the vortices evolve. A definite crosswind threshold for operational use cannot be deduced solely from this study since critical factors such as risk and safety assessment have not yet been taken into account. Copyright © 2011 Royal Meteorological Society
1‐Oxo‐1,3‐dithiolanes—synthesis and stereochemistry
Authors: Pihlaja Kalevi , Sinkkonen Jari , Stájer Gezá , Koch Andreas , Kleinpeter Erich
Published: May 2011

1‐Oxo‐1,3‐dithiolane (4) and its cis‐ and trans‐2‐methyl (5,6), ‐4‐methyl (7,8) and ‐5‐methyl (9,10) derivatives were prepared by oxidizing the corresponding 1,3‐dithiolanes (1–3) with NaIO4 in water. The oxides were purified and their isomers separated using thin layer chromatography. The structural characterization was carried out with 1H and 13C NMR spectroscopy and molecular modelling. The sulfoxides 4–6 and 8–10 attain two S(1) type envelopes (sometimes slightly distorted) the SOax envelope greatly dominating. Cis‐4‐methyl‐1‐oxo‐1,3‐dithiolane is a special case exhibiting both two closely related SOax (30 and 27%) as well as SOeq (21 and 22%) forms [S(1) and C(4) envelopes, respectively]. The relative energies of these conformations, the values of 1H‐1H coupling constants and 1H and 13C chemical shifts were estimated by computational methods and they support well the conclusions based on the experimental data. Copyright © 2011 John Wiley & Sons, Ltd.
Structure elucidation of the dye Acid Red 131: complete 1H, 13C and 15N NMR data assignment
Authors: Schievano Elisabetta , Menegazzo Ileana , Marotta Ester , Mammi Stefano
Published: May 2011

The chemistry of dyes and pigments is relevant to the textile industry, because of the importance to establish the best conditions for the finishing process and to understand the interactions among various compounds to yield the correct hue and nuances. For this reason, the molecular structure of a monoazo acid dye, C.I. Acid Red 131, was elucidated and characterized by homo‐ and hetero‐nuclear NMR, MS, IR and UV spectroscopy techniques. Copyright © 2011 John Wiley & Sons, Ltd.
The First Evidence for Leprosy in Early Mediaeval Scotland: Two Individuals from Cemeteries in St. Andrews, Fife, Scotland, with Evidence for Normal Burial Treatment
Authors: Lunt D. A.
Published: May 2011

The study of skeletal material recovered from excavations at two distinct early mediaeval cemeteries in St. Andrews, Scotland, resulted in the diagnosis of one individual from each cemetery as having had facies leprosa (leprosy). Radiocarbon dating gave a likely date in the 8th century ad for the Hallow Hill skeleton, and the Kirkhill skull was probably from the same period. Both skulls displayed the full range of classic signs of facies leprosa. The bone changes were slightly different in the two, the maxillary alveolus having been more severely affected in the Hallow Hill skull, whereas the posterior palatal area showed greater damage in the skull from Kirkhill. The skeletons were not segregated but buried in the middle of cemeteries used for the general population, thus supporting previous research in both the history of medicine and human bioarchaeology that suggests that people with leprosy were not necessarily stigmatised in the past. Copyright © 2011 John Wiley & Sons, Ltd.
Brilliant imaging
Authors: Jedamzik Ralf
Published: May 2011

Improving the light transmittance of a glass by only a few percent can have a tremendous effect on the quality of an optical system. The optical position and chemical composition of the glass, as well as the choice of raw materials and production principles, determine the absorption rate. This article provides an overview of how the technical demands of high‐end applications influence modern glass production.