bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti–aquaporin‐4 immunoglobulin G into therapeutic antibody
Authors: Tradtrantip Lukmanee , Ratelade Julien , Zhang Hua , Verkman A. S.
Published: August 2012

Objective:

Neuromyelitis optica (NMO) is caused by binding of pathogenic autoantibodies (NMO‐immunoglobulin G [IgG]) to aquaporin‐4 (AQP4) on astrocytes, which initiates complement‐dependent cytotoxicity (CDC) and inflammation. We recently introduced mutated antibody (aquaporumab) and small‐molecule blocker strategies for therapy of NMO, based on prevention of NMO‐IgG binding to AQP4. Here, we investigated an alternative strategy involving neutralization of NMO‐IgG effector function by selective IgG heavy‐chain deglycosylation with bacteria‐derived endoglycosidase S (EndoS).

Methods:

Cytotoxicity and NMO pathology were measured in cell and spinal cord slice cultures, and in mice exposed to control or EndoS‐treated NMO‐IgG.

Results:

EndoS treatment of NMO patient serum reduced by >95% CDC and antibody‐dependent cell‐mediated cytotoxicity, without impairment of NMO‐IgG binding to AQP4. Cytotoxicity was also prevented by addition of EndoS after NMO‐IgG binding to AQP4. The EndoS‐treated, nonpathogenic NMO‐IgG competitively displaced pathogenic NMO‐IgG bound to AQP4, and prevented NMO pathology in spinal cord slice culture and mouse models of NMO.

Interpretation:

EndoS deglycosylation converts pathogenic NMO‐IgG autoantibodies into therapeutic blocking antibodies. EndoS treatment of blood may be beneficial in NMO, and may be accomplished, for example, by therapeutic apheresis using surface‐immobilized EndoS. ANN NEUROL 2013
α‐Synuclein oligomers and clinical implications for Parkinson disease
Authors: Kalia Lorraine V. , Kalia Suneil K. , McLean Pamela J. , Lozano Andres M. , Lang Anthony E.
Published: August 2012

Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long‐held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent, suggesting that another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α‐synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α‐synuclein also forms oligomeric species, with certain conformations being toxic to cells. The mechanisms by which these α‐synuclein oligomers cause cell death are being actively investigated, as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α‐synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications. ANN NEUROL 2013;73:155–169
Fabrication and characterization of tunable wettability surface on copper substrate by poly(ionic liquid) modification via surface‐initiated nitroxide‐mediated radical polymerization
Authors: Long Shijia , Wan Fei , Yang Wu , Guo Hao , He Xiaoyan , Ren Jie , Gao Jinzhang
Published: August 2012

Poly(ionic liquid) surfaces with tunable wettability were successfully prepared on micro/nanoscale CuO/Cu composite substrates by a surface‐initiated nitroxide‐mediated radical polymerization technique. Various characterization techniques including X‐ray photoelectron spectroscopy, cold field emission scanning electron microscopy, and static water contact angle measurement were used to characterize the surfaces for each surface modification step. Kinetic studies revealed that the polymer chain growth from the surface was a controlled/“living” polymerization process. The surface with tunable wettability, reversible switching between hydrophilicity and hydrophobicity can be easily achieved by sequential counteranion exchange. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
In vitro comparative biodegradation analysis of salt‐leached porous polymer scaffolds
Authors: LeBlon Courtney E. , Pai Riyanka , Fodor Caitlin R. , Golding Anne S. , Coulter John P. , Jedlicka Sabrina S.
Published: August 2012

This study presents a comprehensive, side‐by‐side analysis of chemical, thermal, mechanical, and morphological changes in four polymers used in tissue engineering: poly(glycerol‐sebacate) (PGS), poly(lactic acid) (PLA)/poly(ε‐caprolactone) (PCL) blend, poly(lactic‐co‐glycolic acid) (PLGA), and Texin 950, a segmented polyurethane resin (PUR). Polymer foams were created using a salt‐leaching technique and then analyzed over a 16‐week period. Biodegradation was analyzed by examining the morphology, thermal properties, molecular weight, chemical, and mechanical properties using scanning electron microscopy, differential scanning calorimetry, gel permeation chromatography, attenuated total reflectance‐Fourier transform infrared spectroscopy, thermogravimetric analysis, and compression testing. PGS underwent the most rapid degradation and was hallmarked by a decrease in compressive modulus. PLA/PCL blend and PLGA both had rapid initial decreases in compressive modulus, coupled with large decreases in molecular weight. Surface cracks were observed in the PUR samples, accompanied by a slight decrease in compressive modulus. However, as expected, the molecular weight did not decrease. These results confirm that PUR does not undergo significant degradation but may not be suitable for long‐term implants. The biodegradation rates of porous PGS, PLA/PCL blend, and PLGA found in this study can guide their use in tissue engineering and other biomedical applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Recycled acrylonitrile–butadiene–styrene copolymer resin strengthened and toughened by an elastomer/inorganic nanoparticles complex
Authors: Liu Binbin , Lei Hua
Published: August 2012

The properties of recycled acrylonitrile–butadiene–styrene copolymer (rABS) resin deteriorate because of the aging of the acrylonitrile–butadiene–styrene copolymer (ABS) resin during its lifetime; the impact strength, especially, decreases sharply, and the material is commonly brittle. We studied the toughening of rABS by an elastomer and inorganic nanoparticles incorporated into rABS. The results show that the elastomer could restore toughness of the rABS, but it also caused a decrease in the rigidity (flexural modulus); meanwhile, inorganic nanoparticles enhanced the toughness of the rABS only in a limited range for the coalescence issues but also could increase the rigidity of the rABS. This was just the opposite to elastomer. So, we proposed the solution of using an elastomer/inorganic nanoparticle complex to strengthen and toughen rABS. With the incorporation of a 5–8 wt % powdered ABS grafted composition with a rubber content of 70 wt % (referred to as the ABS graft powder) and 2–3 wt % inorganic nanoparticles into rABS, a synergistic effect between elastomer and inorganic nanoparticles was found to significantly benefit the toughness and strength of the rABS resin at the same time, and effective reusability of the rABS was realized. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effect of compatibilizing agents on the mechanical properties of high‐density polyethylene/olive husk flour composites
Authors: Ihemouchen C. , Djidjelli H. , Boukerrou A. , Fenouillot F. , Barres C.
Published: August 2012

The main objective of this research was to investigate the effect on the thermal and mechanical properties of the addition of two different compatibilizing agents, malefic anhydride‐grafted polyethylene (PE) [synthesized in a solution state (MAPE) and commercial (XA255)], to olive husk flour, high‐density polyethylene (HDPE) composites. The composites contain 30 wt % of olive husk flour and a variable proportion of compatibilizer (3, 5, and 7 wt %). The grafting reaction was followed by Fourier transform infrared, and the grafting degree was evaluated by means of titration. The effect of grafting on the thermal properties of MAPE was observed by ATG/DTG. The mechanical and thermal properties of the composite were investigated. A morphological study of the composite reveals that there is a positive effect of compatibilizing agent on interfacial bonding. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Thermal and mechanical properties of sorbitol‐based epoxy resin cured with quercetin and the biocomposites with wood flour
Authors: Shibata Mitsuhiro , Yoshihara Satoru , Yashiro Mio , Ohno Yukito
Published: August 2012

After a bio‐based epoxy resin, sorbitol polyglycidyl ether (SPE) was mixed with a flavonoid, quercetin (QC) in tetrahydrofuran at an optimized epoxy/hydroxy ratio 1/1.2, the obtained SPE/QC solution was mixed with wood flour (WF), prepolymerized at 150°C, and subsequently compressed at 170°C for 3 h to give SPE‐QC/WF biocomposites (WF content:0, 20, 30, 40 wt %). The tan δ peak temperature of SPE‐QC without WF (85.5°C) was higher than that of SPE cured with conventional phenol novolac (81.0°C). In addition, diglycidyl ether of bisphenol A cured with QC had a higher tan δ peak temperature (145.1°C) than that cured with PN (90.8°C). The tan δ peak temperatures (106–113°C) of SPE‐QC/WF biocomposites were significantly higher than that of SPE‐QC. The tensile modulus of SPE‐QC/WF biocomposites increased with increasing WF content. A lower wavenumber shift of carbonyl stretching absorption peak in the FTIR spectrum of SPE‐QC/WF as compared with that of SPE‐QC suggested that hydroxy group of woody component forms hydrogen bonding with carbonyl group of quercetin moiety. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Enthalpy relaxation of photopolymerized multilayered thiol‐ene films
Authors: Shin Junghwan , Nazarenko Sergei , Hoyle Charles E.
Published: August 2012

Multilayered thiol‐ene network films with two and three different components were fabricated by spin coating and photopolymerization. The distinctive glass transition temperatures of each layer component were observed at corresponding glass transition regions of each bulk sample. Sub‐Tg aging of 10‐, 21‐, and 32‐layered thiol‐ene films was investigated in terms of enthalpy relaxation. Enthalpy relaxation of each layer component occurred independently and presented the characteristic time and temperature dependency. Overlapped unsymmetrical bell‐shaped enthalpy relaxation distribution having peak maximum at Tg‐10°C of each layer component was observed, resulting in broad distribution of enthalpy relaxation over wide temperature range. In addition, enthalpy relaxation of each layer component in the multilayered thiol‐ene films was significantly accelerated comparing to that of bulk thiol‐ene samples. Dynamic mechanical thermal properties of multilayered thiol‐ene films also showed two and three separated glass transition temperature. However, for 32‐layered thiol‐ene film consisting of three different layer components, glass transition and damping region are overlapped and the width is extended more than 100°C. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Morphology and mechanical properties of PET/PE blends compatibilized by nanoclays: Effect of thermal stability of nanofiller organic modifier
Authors: Yousfi M. , Soulestin J. , Vergnes B. , Lacrampe M. F. , Krawczak P.
Published: August 2012

Poly(ethylene terephtalate)/poly(ethylene) (PET/PE) blends (80/20 wt %) were prepared by melt‐extrusion and compatibilized by addition of nanoclays. Two commercially available organically modified montmorillonites (Cloisite© 10A and 30B) were chosen as reference and a third one was specially organomodified at lab scale with a thermally stable phosphonium surfactant using conventional cationic exchange reaction. The size of the dispersed polymer phase (PE droplets) and the ductility of the blends depend more on the thermal stability of the surfactant of the organomodified clay than on the enthalpic interactions between the blend components and the surfactants used for the modification of the clays. The highest mechanical properties (yield stress and elongation at break) and the better compatibilization efficiency (smallest dispersed PE droplets) were observed in the presence of phosphonium organomodified montmorillonite compared to other less thermally stable commercial organoclays. The analysis of the thermal stability, morphology, and mechanical properties of PET/PE blends containing the surfactants alone in the absence of clay made it possible to evidence separately the effects of the surfactant and of the nanofiller. The role of the surfactant as compatibilization agent was demonstrated. In the absence of nanofiller, the finest morphological and highest ductility were again obtained with the phosphonium surfactant which is the most thermally stable. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Thermal, mechanical, and rheological properties of poly(ε‐caprolactone)/halloysite nanotube nanocomposites
Authors: Lee Kang‐Suk , Chang Young‐Wook
Published: August 2012

Naturally available halloysite nanotubes (HNTs) with hollow nanotubular structures were used as reinforcement in poly(ε‐caprolactone) (PCL). The PCL/HNT nanocomposites were prepared by melt mixing the polymer with as‐received HNTs up to 10 wt % in an internal batch mixer. Transmission electron microscopy analysis indicated that the HNTs were dispersed uniformly on the nanoscale throughout the PCL matrix. Differential scanning calorimeter studies revealed that the PCL crystallinity was decreased in the nanocomposites, and the HNTs dispersed in the PCL matrix led to an increase in the non‐isothermal crystallization temperature of the PCL. Tensile and dynamic mechanical tests showed great enhancement in strength and stiffness at low HNT content, while still maintaining the ductility of the PCL. The glass transition temperature (Tg) of the pristine PCL was substantially increased with increase in filler loading, which indicates good reinforcing effect imparted by the addition of HNT. Melt rheological studies revealed that the nanocomposites exhibited strong shear thinning behavior, and a percolated network of HNT particles was formed. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
What is an objective structured practical examination in anatomy?
Authors: Yaqinuddin Ahmed , Zafar Muhammad , Ikram Muhammad Faisal , Ganguly Paul
Published: August 2012

Assessing teaching‐learning outcomes in anatomical knowledge is a complex task that requires the evaluation of multiple domains: theoretical, practical, and clinical knowledge. In general, theoretical knowledge is tested by a written examination system constituted by multiple choice questions (MCQs) and/or short answer questions (SAQ). The assessment of practical knowledge (three‐dimensional anatomical concepts) involves oral, spot, or objective structured practical examinations (OSPE). Finally, the application of anatomical knowledge to patients is tested mainly through objective structured clinical examinations (OSCE). The major focus of this study is the OSPE. Although many schools challenge students using this tool in practical examinations in the early phase of the curriculum, the true meaning of OSPE is frequently forgotten and it becomes, in reality, a spot examination. This article, for the first time, describes how the concept of the OSPE has evolved and is currently being used to assess the practical domain of anatomical knowledge in a problem‐based curriculum at Alfaisal University College of Medicine. In addition, it describes the main differences from the spot examination, which is normally used in traditional medical curricula. The authors believe that the OSPE remains the most efficient tool to assess the practical aspects of anatomical knowledge in a system where basic knowledge is integrated with the clinical or functional part of anatomy. However, this contention only holds true if the OSPE process revolves around structured objectives. Anat Sci Educ 6: 125–133. © 2012 American Association of Anatomists.
Bioenergetics and pathway of acid blue 113 degradation byStaphylococcus lentus
Authors: Sekar Sudharshan , Mahadevan Surianarayanan , Shanmugam Bhuvanesh Kumar , Mandal Asit Baran
Published: August 2012

Bioreaction calorimetric studies of degradation of the dye acid blue 113 byStaphylococcus lentusare reported for the first time. The heat released during the dye degradation process can be successfully measured using reaction calorimeter. Power time and oxygen uptake rate (OUR) profile followed each other suggesting that heat profiles could monitor the progress of the dye degradation in biocalorimetry. The shifts observed in power–time profile indicated three distinct phases of the bioprocess indicating simultaneous utilization of glucose (primary) and dye (secondary carbon source). Secretion of azoreductase enzyme enhanced the degradation process. Optimization of aeration and agitation rates was observed to be vital to efficient dye degradation. The degradative pathway for acid blue 113 byS. lentuswas delineated via high‐performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT‐IR), and gas chromatography coupled with mass spectrometry (GC‐MS) analyses. Interestingly the products of degradation were found to have low toxicity, as per cytotoxicity measurements. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
A pumpless perfusion cell culture cap with two parallel channel layers keeping the flow rate constant
Authors: Lee Dong Woo , Yi Sang Hyun , Ku Bosung , Kim Jhingook
Published: August 2012

This article presents a novel pumpless perfusion cell culture cap, the gravity‐driven flow rate of which is kept constant by the height difference of two parallel channel layers. Previous pumpless perfusion cell culture systems create a gravity‐driven flow by means of the hydraulic head difference (Δh) between the source reservoir and the drain reservoir. As more media passes from the source reservoir to the drain reservoir, the source media level decreases and the drain media level increases. Thus, previous works based on a gravity‐driven flow were unable to supply a constant flow rate for the perfusion cell culture. However, the proposed perfusion cell culture cap can supply a constant flow rate, because the media level remains unchanged as the media moves laterally through each channel having same media level. In experiments, using the different fluidic resistances, the perfusion cap generated constant flow rates of 871 ± 27 μL h−1 and 446 ± 11 μL h−1. The 871 and 446 μL h−1 flow rates replace the whole 20 mL medium in the petridish with a fresh medium for days 1 and 2, respectively. In the perfusion cell (A549 cell line) culture with the 871 μL h−1 flow rate, the proposed cap can maintain a lactate concentration of about 2200 nmol mL−1 and an ammonia concentration of about 3200 nmol mL−1. Moreover, although the static cell culture maintains cell viability for 5 days, the perfusion cell culture with the 871 μL h−1 flow rate can maintain cell viability for 9 days. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012
Fast Olefin Metathesis at Low Catalyst Loading
Authors: Peeck Lars H. , Savka Roman D. , Plenio Herbert
Published: August 2012

Reactions of the Grubbs 3rd generation complexes [RuCl2(NHC)(Ind)(Py)] (N‐heterocyclic carbene (NHC)=1,3‐bis(2,4,6‐trimethylphenylimidazolin)‐2‐ylidene (SIMes), 1,3‐bis(2,6‐diisopropylphenylimidazolin)‐2‐ylidene (SIPr), or 1,3‐bis(2,6‐diisopropylphenylimidazol)‐2‐ylidene (IPr); Ind=3‐phenylindenylid‐1‐ene, Py=pyridine) with 2‐ethenyl‐N‐alkylaniline (alkyl=Me, Et) result in the formation of the new N‐Grubbs–Hoveyda‐type complexes 5 (NHC=SIMes, alkyl=Me), 6 (SIMes, Et), 7 (IPr, Me), 8 (SIPr, Me), and 9 (SIPr, Et) with N‐chelating benzylidene ligands in yields of 50–75 %. Compared to their respective, conventional, O‐Grubbs–Hoveyda complexes, the new complexes are characterized by fast catalyst activation, which translates into fast and efficient ring‐closing metathesis (RCM) reactivity. Catalyst loadings of 15–150 ppm (0.0015–0.015 mol %) are sufficient for the conversion of a wide range of diolefinic substrates into the respective RCM products after 15 min at 50 °C in toluene; compounds 8 and 9 are the most catalytically active complexes. The use of complex 8 in RCM reactions enables the formation of N‐protected 2,5‐dihydropyrroles with turnover numbers (TONs) of up to 58 000 and turnover frequencies (TOFs) of up to 232 000 h−1; the use of the N‐protected 1,2,3,6‐tetrahydropyridines proceeds with TONs of up to 37 000 and TOFs of up to 147 000 h−1; and the use of the N‐protected 2,3,6,7‐tetrahydroazepines proceeds with TONs of up to 19 000 and TOFs of up to 76 000 h−1, with yields for these reactions ranging from 83–92 %.
Ruthenium‐Catalyzed Oxidative Coupling/Cyclization of Isoquinolones with Alkynes through CH/NH Activation: Mechanism Study and Synthesis of Dibenzo[a,g]quinolizin‐8‐one Derivatives
Authors: Li Bin , Feng Huiliang , Wang Nuancheng , Ma Jianfeng , Song Haibin , Xu Shansheng , Wang Baiquan
Published: August 2012

The mechanism of [{RuCl2(p‐cymene)}2]‐catalyzed oxidative annulations of isoquinolones with alkynes was investigated in detail. The first step is an acetate‐assisted CH bond activation process to form cyclometalated compounds. Subsequent mono‐alkyne insertion of the RuC bonds of the cyclometalated compounds then takes place. Finally, oxidative coupling of the CN bond of the insertion compounds occurs to afford Ru0 sandwich complexes that undergo oxidation to regenerate the catalytically active RuII complex with the copper oxidant and release the desired dibenzo[a,g]quinolizin‐8‐one derivatives. All of the relevant intermediates were fully characterized and determined by single crystal X‐ray diffraction analysis. The [{RuCl2(p‐cymene)}2]‐catalyzed CH bond functionalization of isoquinolones with alkynes to synthesize dibenzo[a,g]quinolizin‐8‐one derivatives through CH/NH activation was also demonstrated.
Cosmic Chirality both True and False
Authors: Barron Laurence D.
Published: August 2012

The discrete symmetries of parity P, time reversal T, and charge conjugation C may be used to characterize the properties of chiral systems. It is well known that parity violation infiltrates into ordinary matter via an interaction between the nucleons and electrons, mediated by the Z0 particle, that lifts the degeneracy of the mirror‐image enantiomers of a chiral molecule. Being odd under P but even under T, this P‐violating interaction exhibits true chirality and so may induce absolute enantioselection under all circumstances. It has been suggested that CP violation may also infiltrate into ordinary matter via a P‐odd, T‐odd interaction mediated by the (as yet undetected) axion. This CP‐violating interaction exhibits false chirality and so may induce absolute enantioselection in processes far from equilibrium. Both true and false cosmic chirality should be considered together as possible sources of homochirality in the molecules of life. Chirality 24:957‐958, 2012.© 2012 Wiley Periodicals, Inc.
Randomized controlled trial of maintaining quality of life during radiotherapy for advanced cancer
Authors: Clark Matthew M. , Rummans Teresa A. , Atherton Pamela J. , Cheville Andrea L. , Johnson Mary E. , Frost Marlene H. , Miller Janis J. , Sloan Jeff A. , Graszer Karen M. , Haas Jean G. , Hanson Jean M. , Garces Yolanda I. , Piderman Katherine M. , Lapid Maria I. , Netzel Pamela J. , Richardson Jarrett W. , Brown Paul D.
Published: August 2012

BACKGROUND:

Psychosocial interventions often address only 1 domain of quality of life (QOL), are offered to patients with early‐stage cancer, do not include the caregiver, and are delivered after cancer treatment has been completed.

METHODS:

In the current randomized controlled trial, 131 patients with advanced cancer who received radiotherapy and their caregivers were randomly assigned to either a 6‐session, structured, multidisciplinary intervention arm or a standard care arm. The average age of the patients was 58 years, the majority were male (63%), and tumor types varied (gastrointestinal [37%], brain [22%], head and neck [16%], lung [13%], and other [12%]). The six 90‐minute sessions addressed the 5 domains of QOL: cognitive, physical, emotional, social, and spiritual. The in‐person intervention was followed by 10 brief telephone counseling sessions that took place over the next 6 months.

RESULTS:

Of the 117 patients who completed the study, overall QOL (assessed by Functional Assessment of Cancer Therapy‐General [FACT‐G]) at week 4 was significantly higher in the intervention group (n = 54) compared with the standard arm control group (n = 63) (75.2 vs 68.7; P = .02). The 10 brief telephone contacts did not appear to impact QOL because at week 27 the groups had identical QOL (means of 77.6 and 77.7, respectively). There was no effect of the intervention noted on caregiver QOL.

CONCLUSIONS:

Participating in a 6‐session multidisciplinary intervention was found to be effective in maintaining the QOL of patients with advanced cancer who were actively receiving radiotherapy. The QOL and symptom burden of this population is striking, making it important to identify effective QOL strategies to implement in conjunction with cancer care. Cancer 2013. © 2012 American Cancer Society.
BRAF Mutation is associated with early stage disease and improved outcome in patients with low‐grade serous ovarian cancer
Authors: Grisham Rachel N. , Iyer Gopa , Garg Karuna , DeLair Deborah , Hyman David M. , Zhou Qin , Iasonos Alexia , Berger Michael F. , Dao Fanny , Spriggs David R. , Levine Douglas A. , Aghajanian Carol , Solit David B.
Published: August 2012

BACKGROUND:

Low‐grade serous (LGS) ovarian cancer is a chemoresistant disease that accounts for 10% of serous ovarian cancers. Prior studies have reported that 28% to 35% of serous borderline (SB)/LGS ovarian tumors harbor a BRAF mutation, suggesting that BRAF inhibitors may be a rational therapeutic approach for this disease. In the current study, the authors sought to determine whether BRAF or KRAS mutation status was associated with disease stage and/or histology in patients with SB and LGS ovarian cancer.

METHODS:

Genetic profiles were constructed for 75 SB and LGS ovarian tumors to determine BRAF and KRAS mutation status. The incidence and identity of BRAF and KRAS mutations were defined, and the results were correlated with disease stage, response to treatment, and overall survival.

RESULTS:

Of 75 samples examined, 56 tumors (75%) had SB histology, and 19 tumors (25%) had LGS histology. Fifty‐seven percent of tumors harbored either a KRAS mutation (n = 17) or a BRAF mutation (a valine‐to‐glutamate substitution at residue 600 [V600E]; n = 26). The BRAF V600E mutation was associated significantly with early disease stage (stage I/II; P < .001) and SB histology (P = .002). KRAS mutations were not associated significantly with disease stage or histology. Of the 22 patients (29%) who required chemotherapy, 20 had tumors with wild‐type KRAS/BRAF, 2 had KRAS mutant tumors, and none had tumors that harbored a BRAF mutation. All patients with BRAF tumors remained alive at a median follow‐up of 3.6 years (range, 1.9–129.3 months).

CONCLUSIONS:

V600E BRAF mutations were present in 35% of patients who had SB/LGS ovarian cancers. The presence of the BRAF V600E mutation in SB/LGS ovarian cancer was associated with early stage disease and improved prognosis. The authors concluded that patients with SB/LGS ovarian cancer who require systemic therapy are unlikely to have BRAF mutant tumors. Cancer 2013. © 2012 American Cancer Society.
Electrochemical Fabrication and Properties of Highly Ordered Fe‐Doped TiO2 Nanotubes
Authors: Kyeremateng Nana A. , Hornebecq Virginie , Martinez Hervé , Knauth Philippe , Djenizian Thierry
Published: August 2012

Highly‐ordered Fe‐doped TiO2 nanotubes (TiO2nts) were fabricated by anodization of co‐sputtered Ti–Fe thin films in a glycerol electrolyte containing NH4F. The as‐sputtered Ti–Fe thin films correspond to a solid solution of Ti and Fe according to X‐ray diffraction. The Fe‐doped TiO2nts were studied in terms of composition, morphology and structure. The characterization included scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, X‐ray diffraction, UV/Vis spectroscopy, X‐ray photoelectron spectroscopy and Mott–Schottky analysis. As a result of the Fe doping, an indirect bandgap of 3.0 eV was estimated using Tauc’s plot, and this substantial red‐shift extends its photoresponse to visible light. From the Mott–Schottky analysis, the flat‐band potential (Efb) and the charge carrier concentration (ND) were determined to be −0.95 V vs Ag/AgCl and 5.0 ×1019 cm−3 respectively for the Fe‐doped TiO2nts, whilst for the undoped TiO2nts, Efb of −0.85 V vs Ag/AgCl and ND of 6.5×1019 cm−3 were obtained.
Flow cytometric cell‐based assay to preselect antibody constructs for radionuclide conjugation
Authors: Ingargiola M. , Dittfeld C. , Runge R. , Zenker M. , Heldt J.‐M. , Steinbach J. , Cordes N. , Baumann M. , Kotzerke J. , Kunz‐Schughart L. A.
Published: August 2012

Radiolabeled antibodies (Abs) are an attractive tool for targeting and delivering particle emitters for therapy or imaging applications. The labeling of Abs with metal radionuclides requires chelating agents and can cause loss of binding to their ligands. The aim of the present approach was to design an easy‐handling flow cytometric cell‐based assay to evaluate Ab‐binding capacity of conjugates of the therapeutic Ab Cetuximab and to verify the most promising candidate in a competitive radioactive binding experiment. The final setup for flow cytometric assessment of cellular binding capacities of epidermal growth factor receptor (EGFR)/ErbB1‐directed Ab conjugates is based on (a) the selection of a robust cell line model (b) the definition of nonsaturated staining concentrations for the unconjugated reference Ab Cetuximab plus implementation of a reasonable isotype control, and (c) the calculation of relative Ab affinities based on the flow cytometric data. Two (FaDu, SAS) out of the three cell lines with different total and cell surface expression levels of EGFR turned out to be adequate models but the application of one cell line was sufficient to estimate reduced binding capacities of conjugates relative to Cetuximab. Only 1/11 conjugate Abs exhibited a fluorescence signal comparable to unconjugated Cetuximab and was applied for radiolabeling with Yttrium‐90. Unaltered binding affinity of this conjugate was proven in a competitive radioactive Ab‐binding study. We conclude that the flow cytometric assay is reliable and that the relative binding capacity of Cetuximab is neither affected by covalent modification with CHX‐A″‐DTPA (N‐[(R)‐2‐Amino‐3‐(p‐isothiocyanato‐phenyl) propyl]‐trans‐(S,S)‐cyclohexane‐1,2‐diamine‐N,N,N′,N″,N″‐pentaacetic acid) with a final chelator‐to‐Ab ratio of 5 nor by subsequent radiolabeling. [90Y]Y‐CHX‐A″‐DTPA‐Cetuximab thus qualifies for preclinical treatment testing as a prerequisite for therapeutic application. © 2012 International Society for Advancement of Cytometry
Comparative spatiotemporal analysis of Hox gene expression in early stages of intermediate mesoderm formation
Authors: Barak Hila , Preger‐Ben Noon Ella , Reshef Ram
Published: August 2012

Background: Hox genes are key players in AP patterning of the vertebrate body plan and are necessary for organogenesis. Several studies provide evidence for the role Hox genes play during kidney development and especially regarding metanephros initiation and formation. However, the role Hox genes play during early stages of kidney development is largely unknown. A recent study in our lab revealed the role Hoxb4 plays in conferring the competence of intermediate mesodermal cells to respond to kidney inductive signals and express early kidney regulators. Results: As a first step in understanding the role Hox genes play in setting the formation of the pronephros morphogenetic field and the expression of early regulators of kidney development, we studied in detail the expression pattern of 10 Hox genes in relation to the 6th somite axial level, the anterior sharp border of the kidney field. Despite the idea of spatial co‐linearity as exemplified in the Hox gene expression pattern in late developmental stages, a very dynamic spatio‐temporal expression of these genes was found in early stages. Conclusions: Since mesodermal patterning occurs at gastrula stages, the relevance of a “Hox code” at early stages is questioned in this study. Developmental Dynamics 241:1637–1649, 2012. © 2012 Wiley Periodicals, Inc.
Lens regenerates by means of similar processes and timeline in adults and larvae of the newt Cynops pyrrhogaster
Authors: Inoue Takeshi , Inoue Ryo , Tsutsumi Rio , Tada Kikuo , Urata Yuko , Michibayashi Chiaki , Takemura Shota , Agata Kiyokazu
Published: August 2012

Background: It is widely accepted that juvenile animals can regenerate faster than adults. For example, in the case of lens regeneration of the newt Cynops pyrrhogaster, larvae and adults require approximately 30 and 80 days for completion of lens regeneration, respectively. However, when we carefully observed lens regeneration in C. pyrrhogaster at the cellular level using molecular markers in the present study, we found that lens regeneration during the larval stage proceeded at similar speed and by means of similar steps to those in adults. Results: We could not find any drastic difference between regeneration at these two stages, except that the size of the eyes was very different. Conclusions: Our observations suggested that larvae could regenerate a lens of the original size within a shorter time than adults because the larval lens was smaller than the adult lens, but the speed of regeneration was not faster in larvae. In addition, by repeatedly observing the regeneration in one individual transgenic newt that expressed fluorescence specifically in lens fiber cells in vivo and comparing the regeneration process at the embryonic, larval, and postmetamorphosis stages, we confirmed that the regeneration speed was the same at each of these stages in the same individual. Developmental Dynamics 241:1575–1583, 2012. © 2012 Wiley Periodicals, Inc.
Generation of a novel mouse model for the inducible depletion of macrophages in vivo
Authors: Gheryani Nabeia , Coffelt Seth B. , Gartland Alison , Rumney Robin M.H. , Kiss‐Toth Endre , Lewis Claire E. , Tozer Gillian M. , Greaves David R. , Dear T. Neil , Miller Gaynor
Published: August 2012

Macrophages play an essential role in tissue homeostasis, innate immunity, inflammation, and wound repair. Macrophages are also essential during development, severely limiting the use of mouse models in which these cells have been constitutively deleted. Consequently, we have developed a transgenic model of inducible macrophage depletion in which macrophage‐specific induction of the cytotoxic diphtheria toxin A chain (DTA) is achieved by administration of doxycycline. Induction of the DTA protein in transgenic animals resulted in a significant 50% reduction in CD68+ macrophages of the liver, spleen, and bone over a period of 6 weeks. Pertinently, the macrophages remaining after doxycycline treatment were substantially smaller and are functionally impaired as shown by reduced inflammatory cytokine production in response to lipopolysaccharide. This inducible model of macrophage depletion can now be utilized to determine the role of macrophages in both development and animal models of chronic inflammatory diseases. genesis
51:41‐49, 2013. © 2012 Wiley Periodicals, Inc.
Intensity of ecohydrological interactions in reclaimed Mediterranean slopes: effects of run‐off redistribution on plant performance
Authors: Espigares Tíscar , Merino‐Martín Luis , Moreno‐de las Heras Mariano , Nicolau José‐Manuel
Published: August 2012

We have conducted a field experiment to ascertain the role of ecohydrological interactions between run‐off source areas and sink patches in the dynamics of artificial slopes derived from open cast coal mining in central‐eastern Spain. We analysed the effects of run‐off interruption on soil moisture, on the leaf water potential of woody species and on the herbaceous biomass in vegetation patches of three reclaimed slopes subjected to a different disturbance degree resulting from different overland flow volumes running down the slopes. Soil moisture and plant performance were seriously affected by run‐off exclusion, and this effect was more intense as level of disturbance increased. In fact, run‐off redistribution appeared to be determinant for plant performance in the more disturbed slope, whereas the presence of the shrub Genista scorpius appeared to be more determinant for plants in the less disturbed slope. Our results confirm the validity of the Trigger–Transfer–Reserve–Pulse model in artificial slopes during the aggradation process. These results point out the importance of run‐off redistribution between vegetation patches in the evolution of artificial slopes by creating fertility islands that improve the performance of vegetation. Restoration practices in drylands may thus significantly improve if a ‘run‐off expert management’ strategy is adopted. Copyright © 2012 John Wiley & Sons, Ltd.
Constitutive Akt1 signals attenuate B‐cell receptor signaling and proliferation, but enhance B‐cell migration and effector function
Authors: Pierau Mandy , Na Shin‐Young , Simma Narasimhulu , Lowinus Theresa , Marx Alexander , Schraven Burkhart , Bommhardt Ursula H.
Published: August 2012

Ligation of the BCR induces a complex signaling network that involves activation of Akt, a family of serine/threonine protein kinases associated with B‐cell development, proliferation, and tumor formation. Here, we analyzed the effect of enhanced Akt1 signals on B‐cell maturation and function. Unexpectedly, we found that peripheral B cells overexpressing Akt1 were less responsive to BCR stimuli. This correlated with a decrease in Ca2+‐mobilization and proliferation, in an impaired activation of Erk1/2 and mammalian target of rapamycin (mTOR) kinases and poor mobilization of NFATc1 and NF‐κB/p65 factors. In contrast, activation of STAT5 and migration of B cells toward the chemokine SDF1α was found to be enhanced. Akt1 Tg mice showed an altered maturation of peritoneal and splenic B1 B cells and an enhanced production of IgG1 and IgG3 upon immunization with the T‐cell independent Ag TNP‐Ficoll. Furthermore, mice homo‐zygous for Tg Akt1 showed a severe block in the maturation of B‐cell precursors in BM and a strong enrichment of plasma cells in spleen. Altogether, our data reveal that enhanced Akt1 signals modify BCR signaling strength and, thereby, B‐cell development and effector function.
Decreased STAT5 phosphorylation and GATA‐3 expression in NOX2‐deficient T cells: Role in T helper development
Authors: Shatynski Kristen E. , Chen Haiyan , Kwon Jaeyul , Williams Mark S.
Published: August 2012

Absence of phagocyte NADPH oxidase (NOX2) activity causes chronic granulomatous disease (CGD), a primary immunodeficiency characterized by recurrent bacterial infections. In contrast to this innate immune deficit, CGD patients and animal models display a predisposition toward autoimmune disease and enhanced response to Helicobacter pylori and influenza virus infection. These data imply an altered, perhaps augmented, adaptive immune response in CGD. As previous data demonstrated functional NOX2 expression in T cells, our goal here was to determine if NOX2‐deficient T cells are inherently altered in their responses. Activation of purified naive CD4+ T cells from NOX2‐deficient mice led to augmented IFN‐γ and diminished IL‐4 production and an increased ratio of expression of the TH1‐specific transcription factor T‐bet versus the TH2‐specfic transcription factor GATA‐3, consistent with a TH1 skewing of naïve T cells. Selective inhibition of TCR‐induced STAT5 phosphorylation was identified as a potential mechanism for skewed T helper differentiation. Exposure to antioxidants inhibited, while pro‐oxidants augmented TH2 cytokine secretion and STAT5 phosphorylation, supporting the redox dependence of these signaling changes. These data suggest that TCR‐induced ROS generation from NOX2 activation can regulate the adaptive immune response in a T‐cell‐inherent fashion, and propose a possible role for redox signaling in T helper differentiation.
Rapid screening and determination of 4‐chloroamphetamine in saliva by paper spray‐mass spectrometry and capillary electrophoresis‐mass spectrometry
Authors: Jhang Chih‐Sheng , Lee Hsun , He Yi‐San , Liu Ju‐Tsung , Lin Cheng‐Huang
Published: August 2012

A novel drug‐screening system, consisting of paper spray‐MS (PS‐MS) and a CE‐ESI‐MS method was developed. This system can be easily switched either to PS‐MS for rapidly screening samples or to the traditional CE‐ESI‐MS method for separation and to obtain detailed mass spectral information, while sharing the same mass spectrometer. In the former case, when a sharp (15°‐tip) chromatography paper was used, the optimized distance from the paper tip to the mass inlet was 7.7 mm, whereas the optimized distance for the CE‐ESI tip was ∼13.5 mm. Using 4‐chloroamphetamine as a model compound, the LODs for PS‐MS and CE‐ESI‐MS were determined to ∼0.1 and 0.25 ppm, respectively. Comparisons of results obtained using PS‐MS and CE‐ESI‐MS and the experimental conditions are described.
A protocol for stripping and reprobing of Western blots originally developed with colorimetric substrate TMB
Authors: Kar Parmita , Agnihotri Saurabh Kumar , Sharma Archana , Sachan Rekha , Lal Bhatt Madan , Sachdev Monika
Published: August 2012

Western blotting is a widely used analytical technique for detection of specific protein(s) in a given sample of tissue/cell homogenate or extract. Both chemiluminescence (CL) and colorimetric detections can be used for imaging Western blots. Colorimetric substrates offer background free, sensitive, and clean imaging results directly on the blotted membrane and provides more accurate profile with respect to prestained marker. However, blots stained with colorimetric substrates cannot be reused since no stripping protocols have been reported for such blots, thus limiting their reuse for detection of another protein. In the present study, for the first time, we report a novel method of stripping Western blots developed with the colorimetric substrate TMB for detection of a low‐abundant protein and reprobing of these blots after stripping for detection of a more abundant protein through CL procedure. The stripping procedure utilizes a stripping buffer consisting of β‐mercaptoethanol, SDS, and Tris‐HCl and a washing buffer consisting of PBS added with 0.1% Tween‐20 involves a series of steps and facilitates accurate detection of the second protein (i.e., more abundant protein) in the stripped blot through CL. The protocol is reproducible and facilitates saving of precious clinical samples, in addition to saving cost and time as compared to the existing procedures.
Design of nonbinary quasi‐cyclic low‐density parity‐check codes by maximising the minimum distance
Authors: Liu Lei , Zhou Wuyang , Zhou Shengli
Published: August 2012

In this paper, we propose a construction method of nonbinary quasi‐cyclic low‐density parity‐check (QC‐LDPC) codes. The shift offset values of the circulant permutation submatrices are selected not only by maximising the girth but also by maximising the minimum distance upper bound. The proposed method provides a more rational optimisation way than only maximising the girth.Copyright © 2012 John Wiley & Sons, Ltd.
Late Viséan coral fringing reef at Tiouinine (Morocco): implications for the role of rugose corals as building organisms in the Mississippian
Authors: Rodríguez S. , Somerville I. D. , Said I. , Cózar P.
Published: August 2012

The excellent exposure and preservation of a fringing reef located at Tiouinine, near Khenifra (Central Moroccan Meseta) is a unique case in the Mississippian which allows us to distinguish different facies belts of a classical coral framework reef. The reefal facies rest on thin basal siliciclastic rocks which rest unconformably on Ordovician sandstones. There is a complete zonation from tidal deposits of the inner shelf to reefal talus. Tidal deposits occur in a narrow band and are composed of sandy packstones. There is a transition to reef flat deposits composed of skeletal packstone–grainstone with a patchy distribution of coral colonies. There is also a transitional change to core reef facies that are composed of fasciculate and massive corals reinforced by algal masses around the corals and microbial micropeloidal mudstone to wackestone coating the corals and algae. The spaces between the corals and algal masses are infilled by crinoidal and coral grainstone. The dominant building organisms are rugose corals of the genera Siphonodendron, Lithostrotion, Diphyphyllum and Tizraia, as well as contributions from the tabulate genera Michelinia, Multithecopora and Syringopora. The proximal reef talus is represented by skeletal packstone and rudstone containing highly diverse bioclasts, with corals, crinoids, foraminifers, gastropods and bivalves, as well as large fragments of reworked coral colonies and some coral colonies in growth position. These beds show erosive surfaces and amalgamation of beds. A somewhat more distal reef talus is represented by well‐bedded marly limestones containing mainly crinoids and branches of fasciculate corals. The existence of a well‐preserved coral reef in the late Viséan in Morocco provides further evidence that rugose and tabulate corals did build reefs after the Late Devonian reef extinction event. Copyright © 2012 John Wiley & Sons, Ltd.
Distinct laterality alterations distinguish mild cognitive impairment and Alzheimer's disease from healthy aging: Statistical parametric mapping with high resolution MRI
Authors: Long Xiaojing , Zhang Lijuan , Liao Weiqi , Jiang Chunxiang , Qiu Bensheng ,   the Alzheimer's Disease Neuroimaging Initiative
Published: August 2012

Laterality of human brain varies under healthy aging and diseased conditions. The alterations in hemispheric asymmetry may embed distinct biomarkers linked to the disease dynamics. Statistical parametric mapping based on high‐resolution magnetic resonance imaging (MRI) and image processing techniques have allowed automated characterization of morphological features across the entire brain. In this study, 149 subjects grouped in healthy young, healthy elderly, mild cognitive impairment (MCI), and Alzheimer's disease (AD) were investigated using multivariate analysis for regional cerebral laterality indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume measured on high‐resolution MR images. Asymmetry alteration of MCI and AD were characterized by marked region‐specific reduction, while healthy elderly featured a distinct laterality shift in the limbic system in addition to regional asymmetry loss. Lack of the laterality shift in limbic system and early loss of asymmetry in entorhinal cortex may be biomarkers to identify preclinical AD among other dementia. Multivariate analysis of hemispheric asymmetry may provide information helpful for monitoring the disease progress and improving the management of MCI and AD. Hum Brain Mapp 34:3400–3410, 2013. © 2012 Wiley Periodicals, Inc.