bluuebunny/crossref_metadata_2025 huggingface dataset:
Pitt–Hopkins Mouse Model has Altered Particular Gastrointestinal Transits In Vivo
Authors: Grubišić Vladimir , Kennedy Andrew J. , Sweatt J. David , Parpura Vladimir
Published: February 2015

Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder, classified as an autism spectrum disorder that is caused by the haploinsufficiency of Transcription Factor 4 (TCF4). The most common non‐neurological symptoms in PTHS patients are gastrointestinal (GI) disturbances, mainly gastroesophageal reflux and severe constipation (in about 30 and 75% of PTHS patients, respectively). We hypothesized that the recently recognized mouse model of PTHS will exhibit problems with their gut function. We conducted series of in vivo tests on 15‐ to 19‐ week old male mice, heterozygous for the TCF4 functional deletion, mimicking the TCF4 haploinsufficiency in PTHS patients, and their wild type littermates. Data collection and initial analysis were performed blindly, that is, the genotyping key was received after the mean values were calculated for each individual animal, and then mean/median of each group was subsequently calculated. Body weight, fecal pellet output, and fluid content were similar between the groups, indicating normal gross growth of PTHS mice and their overall physiological GI motility and intestinal secretion/absorption. There were no significant differences in gut length and gross appearance pointing out that PTHS mice have normal gut in gross anatomical terms. However, the assessment of gut transit indicates that, while whole‐gut transit velocity was similar between the groups, the upper GI and distal colon transit velocities were significantly reduced in the PTHS mice. This is the first evidence of specific gut related problems in the PTHS mice. Our study also validates the TCF4 functional knockout mice as an animal model to study PTHS‐associated GI disturbances. Autism Res 2015, 8: 629–633. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
In situ measurements of radiofrequency exposure levels in Greece from 2008 to 2013: A multi‐parametric annual analysis
Authors: Christopoulou Maria , Karabetsos Efthymios
Published: February 2015

From 2008 through 2013, more than 6,000 in situ frequency selective audits, in the proximity of base stations, were conducted throughout Greece by the Greek Atomic Energy Commission (EEAE), in order to verify exposure limit compliance. EEAE is the competent national authority for protection of the general public against artificially produced non‐ionizing radiation. This paper presents the first post processing and multi‐parametric year statistical analysis of in situ measurement data corresponding to 4,705 audits in the whole country, compared to general public exposure levels, according to Greek legislation. The aim is to derive nationwide conclusions for the characterization of general public exposure to radiofrequency electromagnetic fields, during the last 6 years. The results' presentation includes electric field exposure ratios referring to broadband and frequency selective measurements at the highest exposure measurement point. Statistical analysis is applied to assist the data presentation and evaluation, based on selected criteria and classification parameters, including: (i) year (2008–2013); (ii) environment (urban/suburban/rural); (iii) frequency bands of selected common telecommunication services (e.g., TV, FM, GSM, DCS, UMTS); and (iv) number of service providers installed at the same site. In general, measurement results revealed that the vast majority of exposure values were below reference levels for general public exposure, as defined by Greek legislation. Data are constantly updated with the latest measurements, including emerging wireless technologies. Bioelectromagnetics. 36:325–329, 2015. © 2015 Wiley Periodicals, Inc.
Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels
Authors: Liu Min , Yao Xu‐Dong , Li Wei , Geng Jiang , Yan Yang , Che Jian‐Ping , Xu Yun‐Fei , Zheng Jun‐Hua
Published: February 2015

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy. © 2015 BioFactors, 41(1):52–57, 2015
Microtubule‐based nanomaterials: Exploiting nature's dynamic biopolymers
Authors: Bachand George D. , Spoerke Erik D. , Stevens Mark J.
Published: February 2015

For more than a decade now, biomolecular systems have served as an inspiration for the development of synthetic nanomaterials and systems that are capable of reproducing many of unique and emergent behaviors of living systems. One intriguing element of such systems may be found in a specialized class of proteins known as biomolecular motors that are capable of performing useful work across multiple length scales through the efficient conversion of chemical energy. Microtubule (MT) filaments may be considered within this context as their dynamic assembly and disassembly dissipate energy, and perform work within the cell. MTs are one of three cytoskeletal filaments in eukaryotic cells, and play critical roles in a range of cellular processes including mitosis and vesicular trafficking. Based on their function, physical attributes, and unique dynamics, MTs also serve as a powerful archetype of a supramolecular filament that underlies and drives multiscale emergent behaviors. In this review, we briefly summarize recent efforts to generate hybrid and composite nanomaterials using MTs as biomolecular scaffolds, as well as computational and synthetic approaches to develop synthetic one‐dimensional nanostructures that display the enviable attributes of the natural filaments. Biotechnol. Bioeng. 2015;112: 1065–1073. © 2015 Wiley Periodicals, Inc.
A validated sensitive HPLC‐MS/MS method for quantification of a potential hypnotic drug MT502 and its application to a pharmacokinetic study in rat
Authors: Zhang Fang‐Fang , Cheng Ying , Wan Ning , Jing Zi‐Wei , Ju Jia , Jia Yi‐Yang , Zhou Si‐Yuan , Zhang Bang‐Le
Published: February 2015

A rapid, sensitive HPLC‐MS/MS method was established and validated to assay the concentration and pharmacokinetic profile of MT502, a promising hypnotic drug. The plasma sample was treated by a liquid–liquid extraction and separated on a kromasil C18 column at an isocratic flow rate of 0.3 mL/min using methanol and 0.1% formic acid in water (75:25, v/v) as mobile phase. The mass spectrometric detection was carried out using a triple‐quadrupole system via positive electrospray ionization. Multiple reaction monitoring was used for quantitation of m/z transitions from 261 to 188 for MT502 and from 247 to 188 for MT501 (internal standard). Good linearity was achieved over the concentration range of 1–1000 ng/mL and 10–5000 ng/mL with lower limit of quantification of 0.30 and 0.80 ng/mL. The intra‐ and inter‐day precisions, accuracy, recovery and stability were satisfactory for the concentration test. The above method can be used for a pharmacokinetic study at doses of 1, 5 and 20 mg/kg. Results indicated that MT502 had rapid absorption, rapid elimination and linear pharmacokinetic properties within the range of the tested intragastric dose. This developed HPLC‐MS/MS method was successfully applied to a pharmacokinetic study of MT502 for the first time and was demonstrated to be simple and sensitive. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis of Sn‐Beta with Exclusive and High Framework Sn Content
Authors: van der Graaff William N. P. , Li Guanna , Mezari Brahim , Pidko Evgeny A. , Hensen Emiel J. M.
Published: February 2015

Sn‐Beta zeolite was prepared by acid dealumination of Beta zeolite, followed by dehydration and impregnation with anhydrous SnCl4. The formation of extraframework Sn (EFSn) species was prevented by the removal of unreacted SnCl4 in a methanol washing step prior to calcination. The resulting Sn‐Beta zeolites were characterized by X‐ray diffraction, Ar physisorption, NMR, UV/Vis, and FTIR spectroscopy. These well‐defined Lewis acid zeolites exhibit good catalytic activity and selectivity in the conversion of 1,3‐dihydroxyacetone to methyl lactate. Their performance is similar to a reference Sn‐Beta zeolite prepared by hydrothermal synthesis. Sn‐BEA zeolites that contain EFSn species exhibit lower catalytic activity; the EFSn species also catalyze formation of byproducts. DFT calculations show that partially hydrolyzed framework Sn‐OH species (open sites), rather than the tetrahedral framework Sn sites (closed sites), are the most likely candidate active sites for methyl lactate formation.
Methode zur Untersuchung der Partikelbewegung in diskontinuierlich und kontinuierlich arbeitenden Wirbelschichten
Authors: Idakiev Vesselin V. , Mörl Lothar
Published: February 2015

Ein neuartiges Verfahren, das magnetische Monitoring, wurde zur Bestimmung der Partikelbewegung eines magnetisch markierten Teilchens im Partikelkollektiv in diskontinuierlich sowie kontinuierlich arbeitenden Wirbelschichten eingesetzt. Die Position in x‐, y‐ und z‐Richtung und die räumliche Ausrichtung des Markers wird gemessen. Daraus lassen sich die Geschwindigkeit, die Beschleunigung, die auf die Partikel wirkenden Kräfte und Energien sowohl für die Translation als auch für die Rotation der Partikel berechnen. In der vorliegenden Arbeit wurden die Bewegungskennwerte der Partikel ermittelt. Des Weiteren wurde der Einfluss von verschiedenen Apparate‐ und Betriebsparametern auf die Bewegungskennwerte untersucht.
Gender‐Related Mortality and In‐Hospital Complications Following ST‐Segment Elevation Myocardial Infarction: Data From a Primary Percutaneous Coronary Intervention Cohort
Authors: Laufer‐Perl Michal , Shacham Yacov , Letourneau‐Shesaf Sivan , Priesler Ofir , Keren Gad , Roth Arie , Steinvil Arie
Published: February 2015

Background

The increased mortality related to female gender in ST‐segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) has been reported from various patient cohorts and treatment strategies with controversial results. In the present work, we evaluated the impact of female gender on mortality and in‐hospital complications among a specific subset of consecutive STEMI patients managed solely by PPCI.

Hypothesis

Female gender is not an independent predicor for mortality among STEMI patients.

Methods

We performed a retrospective, single‐center observational study that included 1346 consecutive STEMI patients undergoing PPCI, of which 1075 (80%) were male. Patient's records were evaluated for 30‐day mortality, in‐hospital complications, and long‐term mortality over a mean period of 2.7 ± 1.6 years.

Results

Compared with males, females were older (69 ± 13 vs 60 ± 13 years, P < 0.001), had a significantly higher rate of baseline risk factors, and had prolonged symptom duration (460 ± 815 minutes vs 367 ± 596 minutes, P = 0.03). Females suffered from more in‐hospital complications and had higher 30‐day mortality (5% vs 2%, P = 0.008) as well as higher overall mortality (12.5% vs 6%, P < 0.001). In spite of the significant mortality risk in unadjusted models, a multivariate adjusted Cox regression model did not demonstrate that female gender was an independent predictor for mortality among STEMI patients.

Conclusions

Among patients with STEMI treated by PPCI, female gender is associated with a higher 30‐day mortality and complications rates compared to males. Following multivariate analysis, female gender was not a significant predictor of long‐term death following STEMI.
Treatment‐related toxicities in older adults with head and neck cancer: A population‐based analysis
Authors: O'Neill Caitriona B. , Baxi Shrujal S. , Atoria Coral L. , O'Neill James P. , Henman Martin C. , Sherman Eric J. , Lee Nancy Y. , Pfister David G. , Elkin Elena B.
Published: February 2015

BACKGROUND

Despite advantages in terms of cancer control and organ preservation, the benefits of chemotherapy and radiation therapy (CTRT) may be offset by potentially severe treatment‐related toxicities, particularly in older patients. The objectives of this study were to assess the types and frequencies of toxicities in older adults with locally or regionally advanced head and neck squamous cell carcinoma (HNSCC) who were receiving either primary CTRT or radiation therapy (RT) alone.

METHODS

With Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims, patients who were 66 years old or older with locally advanced HNSCC, were diagnosed from 2001 to 2009, and received CTRT or RT alone were identified. Differences in the frequency of toxicity‐related hospital admissions and emergency room visits as well as feeding tube use were examined, and controlling for demographic and disease characteristics, this study estimated the impact of chemotherapy on the likelihood of toxicity.

RESULTS

Among patients who received CTRT (n = 1502), 62% had a treatment‐related toxicity, whereas 46% of patients who received RT alone (n = 775) did. When the study controlled for demographic and disease characteristics, CTRT patients were twice as likely to experience an acute toxicity in comparison with their RT‐only peers. Fifty‐five percent of CTRT patients had a feeding tube placed during or after treatment, whereas 28% of the RT‐only group did.

CONCLUSIONS

In this population‐based cohort of older adults with HNSCC, the rates of acute toxicities and feeding tube use in patients receiving CTRT were considerable. It is possible that for certain older patients, the potential benefit of adding chemotherapy to RT does not outweigh the harms of this combined‐modality therapy. Cancer 2015. © 2015 American Cancer Society. Cancer 2015;121:2083–2089. © 2015 American Cancer Society.
Hydrothermal Targeted‐Explosion Synthesis of Hollow/Porous Upconversion Nano‐ and Microcrystals with Potential for Luminescent Displays and Biological Imaging
Authors: Qiu Peiyu , Sun Rongjin , Gao Guo , Chen Bin , Zhang Chunlei , Yin Ting , Zhang Jingpu , Fang Shan , Cui Daxiang
Published: February 2015

A facile, one‐pot, hydrothermal ‘targeted‐explosion’ strategy was developed to construct β‐NaGdF4 and β‐NaYF4 hollow/porous upconversion nano‐ and microcrystals. We found that potassium sodium tartrate (PST) strongly complexes rare earth ions, which can reduce the reaction speed between rare earth ions and fluorine ions, leading to size‐ and morphology‐controlled crystals in a hydrothermal synthesis. Moreover, we simulated the ‘targeted‐explosion’ reaction process through structural mechanics finite element calculations to validate the feasibility of a ‘layer‐by‐layer blasting’ mechanism. Finally, we fabricated various models to show the potential of these materials for luminescent displays and as rare earth illuminants excited by near‐infrared light. In addition, the synthesized hollow/porous upconversion crystals were used for different types of biological imaging.
Temperature‐Dependent Immobilization of a Tungsten Peroxo Complex That Catalyzes the Hydroxymethoxylation of Olefins
Authors: Chen Jizhong , Hua Li , Chen Chen , Guo Li , Zhang Ran , Chen Angjun , Xiu Yuhe , Liu Xuerui , Hou Zhenshan
Published: February 2015

A tungsten peroxo complex stabilized by the bidentate picolinato ligand has been synthesized and then immobilized successfully on imidazole‐functionalized silica. The immobilized tungsten‐based catalyst was employed as an efficient catalyst for the one‐pot synthesis of β‐alkoxy alcohols from olefins and methanol with H2O2. Regarding the catalyst evaluation and the results of characterization by the various methods, it was demonstrated that the immobilization of tungsten peroxo complex was highly temperature‐dependent. The tungsten peroxo complex can dissociate and diffuse into the liquid phase at reaction temperature, resulting in a homogeneous reaction. Nevertheless, the catalytically active species was anchored on the imidazole‐functionalized silica by hydrogen bonding as the temperature was lowered to 0 °C after the reaction, which thus offered a highly effective approach for recycling the catalyst for consecutive cycles. In addition, various olefins can be converted to the corresponding β‐alkoxy alcohols with good conversion and selectivity under relative mild conditions by H2O2.
Three‐Dimensional Arrays of 1D MnO2 Nanocrystals for All‐Solid‐State Asymmetric Supercapacitors
Authors: Dubal Deepak P. , Holze Rudolf , Gomez‐Romero Pedro
Published: February 2015

Reported is the synthesis of 3D hierarchical structures based on one‐dimensional MnO2 nanobuilding blocks (nanorods, nanowires, and nanoneedles) by means of a facile and scalable coprecipitation method and their use as electrodes for the assembly of all‐solid‐state supercapacitors. Asymmetric devices were also assembled by using these nanostructured MnO2 materials as the positive electrode and reduced graphene oxide (rGO) as the negative electrode with a polymeric gel electrolyte. The asymmetric cells successfully extend the working voltage windows beyond 1.4 V and allowed for a maximum voltage of 1.8 V. An asymmetric device based on hierarchical nanoneedle‐like MnO2 and rGO achieved a maximum specific capacitance of 99 F g−1 at a scan rate of 10 mV s−1 with a stable operational voltage of 1.8 V. This high value allowed for a large specific energy of 24.12 Wh kg−1.
Interpersonal Subtypes and Therapy Response in Patients Treated for Posttraumatic Stress Disorder
Authors: König Julia , Onnen Margarete , Karl Regina , Rosner Rita , Butollo Willi
Published: February 2015

Interpersonal traits may influence psychotherapy success. One way of conceptualizing such traits is the interpersonal circumplex model. In this study, we analyse interpersonal circumplex data, assessed with the Inventory of Interpersonal Problems (Horowitz, Strauß, & Kordy, 1994) from a randomized study with 138 patients suffering from posttraumatic stress disorder after trauma in adulthood. The study compared cognitive processing therapy and dialogical exposure therapy, a Gestalt‐based intervention. We divided the interpersonally heterogeneous sample according to the quadrants of the interpersonal circumplex. The division into quadrants yielded subgroups that did not differ in their general psychological distress, but the cold‐submissive quadrant tended to exhibit higher posttraumatic stress disorder symptom severity and interpersonal distress than the other three. There was also a trend for patients in different quadrants to be affected differently by the treatments. Correlation analyses supported these results: in cognitive processing therapy, more dominant patients had more successful therapies, while in dialogical exposure therapy, success was not correlated with interpersonal style. Results indicate that especially patients with cold interpersonal styles profited differentially from the two treatments offered. Dividing samples according to the interpersonal circumplex quadrants seems promising. Copyright © 2015 John Wiley & Sons, Ltd.

Key Practitioner Message:

Interpersonal traits may contribute to psychotherapy outcome.

Dividing the sample according to the quadrants of the interpersonal circumplex, as opposed to cluster analysis, yielded promising results.

Patients higher in dominance fared better with cognitive processing therapy, while interpersonal style had no correlations with therapy success in dialogical exposure therapy.
Pressure‐Driven Enthalpic and Lifshitz Transition in 122‐Pnictides
Authors: Quader K.F. , Widom M.
Published: February 2015

Iron‐arsenic pnictides are a class of compounds in which strong Coulomb interactions manifest in novel prop¬erties. We discuss basic ideas behind a Lifshitz transition and review salient properties of 122‐pnictides (AFe2As2; A = Ca, Sr, Ba, Ra). Using T = 0 first principles total energy calculations, as a function of hydro¬static pressure, we show that several pressure‐driven anomalies, and the tetragonal (T) to collapsed tetragonal (cT) phase transition in the 122‐pnictides family, can be understood as consequences of Lifshitz transitions arising from nontrivial changes in Fermi surface topology. We also show that several features found in our calculations, namely, enthalpic, magnetic and T‐cT transitions, are universal to the 122‐pnictides. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fine needle aspiration of thyroid nodules in the pediatric population: A 12‐year cyto‐histological correlation experience at north shore‐long island jewish health system
Authors: Lale Seema A. , Morgenstern Nora N. , Chiara Sugrue , Wasserman Patricia
Published: February 2015

Background

Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature.

Methods

13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology‐surgical follow‐up.

Results

Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U‐category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy‐four children had surgical follow‐up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category.

Conclusions

To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to “follow‐up and repeat” may not apply to the pediatric population. Surgery may be reasonable in these categories instead. Diagn. Cytopathol. 2015;43:598‐604. © 2015 Wiley Periodicals, Inc.
Reduced evapotranspiration from leaf beetle induced tamarisk defoliation in the Lower Virgin River using satellite‐based energy balance
Authors: Liebert Ryan , Huntington Justin , Morton Charles , Sueki Sachiko , Acharya Kumud
Published: February 2015

Tamarisk (Tamarix spp.) is an invasive shrubby tree native to Eurasia. Since its introduction to the United States, it has established itself along Southwestern American riparian systems. Control programs aimed at removing tamarisk were initiated in an effort to restore riparian areas, and potentially salvage water. Biological control of tamarisk with the Diorhabda spp. (leaf beetles) defoliates tamarisk and reduces evapotranspiration (ET). In 2009, the beetle arrived at Mesquite, Nevada, along the Virgin River, and dispersed to the Lower Virgin River riparian area in 2011. This study estimates reduced Lower Virgin River riparian ET caused by leaf beetle activity. Multi‐temporal spectral angle mapper was used to detect established leaf beetle communities in the Lower Virgin River riparian area. The Mapping Evapotranspiration at High Resolution with Internal Calibration (METRIC) land surface energy balance model was used to estimate Lower Virgin River riparian ET. METRIC ET results were compared with eddy covariance ET estimates made in tamarisk along the Lower Virgin River. Comparisons indicated that METRIC accurately estimates pre‐beetle ET and post‐beetle reduced ET. The 2007–2010 (pre‐beetle) average ET for the Lower Virgin River riparian area was 1245 mm/yr compared with 1041 mm/yr for the 2011–2012 (post‐beetle) period. Given the 4700 acre riparian area, leaf beetle induced defoliation results in a mean annual ET reduction of 3161 acre‐ft. In 2011 and 2012, volumetric reductions to ET were estimated to be 817 and 5505 acre‐ft, respectively. The METRIC model was shown to be a useful tool for monitoring ET during pre‐beetle and post‐beetle defoliation periods. Copyright © 2015 John Wiley & Sons, Ltd.
CD28/CTLA‐4/B7 costimulatory pathway blockade affects regulatory T‐cell function in autoimmunity
Authors: Vogel Isabel , Kasran Ahmad , Cremer Jonathan , Kim Yoo‐Jin , Boon Louis , Van Gool Stefaan W. , Ceuppens Jan L.
Published: February 2015

Naïve T cells require B7/CD28 costimulation in order to be fully activated. Attempts to block this pathway have been effective in preventing unwanted immune reactions. As B7 blockade might also affect Treg cells and interfere with negative signaling through membrane CTLA‐4 on effector T (Teff) cells, its immune‐modulatory effects are potentially more complex. Here, we used the mouse model of multiple sclerosis (MS), EAE, to study the effect of B7 blockade. An effective therapy for MS patients has to interfere with ongoing inflammation, and therefore we injected CTLA‐4Ig at day 7 and 9 after immunization, when myelin‐reactive T cells have been primed and start migrating toward the CNS. Surprisingly, B7 blockade exacerbated disease signs and resulted in more severe CNS inflammation and demyelination, and was associated with an enhanced production of the inflammatory cytokines IL‐17 and IFN‐γ. Importantly, CTLA‐4Ig treatment resulted in a transient reduction of Ki67 and CTLA‐4 expression and function of peripheral Treg cells. Taken together, B7 blockade at a particular stage of the autoimmune response can result in the suppression of Treg cells, leading to a more severe disease.
Overexpression of CD85j in TNBC patients inhibits Cetuximab‐mediated NK‐cell ADCC but can be restored with CD85j functional blockade
Authors: Roberti María P. , Juliá Estefanía P. , Rocca Yamila S. , Amat Mora , Bravo Alicia I. , Loza José , Coló Federico , Loza Carlos M. , Fabiano Verónica , Maino Mercedes , Podhorzer Ariel , Fainboim Leonardo , Barrio María M. , Mordoh José , Levy Estrella M.
Published: February 2015

Clinical studies suggest that triple negative breast cancer (TNBC) patients with epidermal growth factor receptor (EGFR)‐expressing tumors could benefit from therapy with Cetuximab, which targets EGFR. NK cells are the primary effectors of antibody (Ab)‐dependent cell‐mediated cytotoxicity (ADCC) and thus play a role in Ab‐based therapies. We have previously described diminished levels of Cetuximab‐mediated ADCC in vitro in patients with advanced breast cancer. Here, we investigated the potential causes of this NK‐cell functional deficiency. We characterized NK‐cell activating/inhibitory receptors in the peripheral blood of breast cancer patients and found CD85j inhibitory receptor overexpression. The capacity of NK cells to perform Cetuximab‐triggered ADCC against TNBC cells correlated inversely with CD85j expression, even in the presence of the stimulatory cytokines IL‐2 or IL‐15. Hence, patients expressing high levels of CD85j had an impaired ability to lyse TNBC cells in the presence of Cetuximab. We also found that CD85j overexpression was associated with HLA‐I and soluble HLA‐G expression by tumors. A CD85j functional blockade with a CD85j antagonist Ab restored ADCC levels in breast cancer patients and reverted this negative effect. Our data suggest that strategies that overcome the hurdles of immune activation could improve Cetuximab clinical efficacy.
Amine‐bis(phenolato)cobalt(II) Catalysts for the Formation of Organic Carbonates from Carbon Dioxide and Epoxides
Authors: Reiter Marina , Altenbuchner Peter T. , Kissling Stefan , Herdtweck Eberhardt , Rieger Bernhard
Published: February 2015

New monometallic amine‐bis(phenolato)cobalt(II) [(ONNO)RCoII] (R = CMe2Ph; Cl; Br) complexes have been synthesized and fully characterized including X‐ray crystallographic analysis. These CoII complexes show good activity for the formation of cyclic propylene carbonate in combination with tetrabutylammonium bromide (TBAB) as a co‐catalyst. The reaction parameters such as carbon dioxide pressure, co‐catalyst loadings and temperature were varied to determine the ideal reaction conditions. These catalysts were also employed in copolymerization reactions of cyclohexene oxide/CO2 and propylene oxide/CO2. [(ONNO)ClCoII]*(MeOH) was found to effectively copolymerize cyclohexene oxide (CHO) and CO2. This is the first reported amine‐bis(phenolato) cobalt(II) complex to be active in the copolymerization of CO2 and CHO. In‐depth stability studies were conducted (Evan's method) to validate CoII as the active species required for copolymerization. End‐group analysis via NMR, ESI‐MS and MALDI‐TOF revealed the presence of 4‐(dimethylamino)pyridine (DMAP) and methoxy terminated chains.
Reactions of [Cp2Ti(η2‐Me3SiC2SiMe3)] with 1,4‐Bis(diphenylphosphanyl)but‐2‐yne: Coupling and Isomerization versus Phosphorylation
Authors: Altenburger Kai , Reiß Fabian , Schubert Kathleen , Baumann Wolfgang , Spannenberg Anke , Arndt Perdita , Rosenthal Uwe
Published: February 2015

The reactions of [Cp2Ti(η2‐Me3SiC2SiMe3)] (1; Cp = η5‐cyclopentadienyl) with 1,4‐bis(diphenylphosphanyl)but‐2‐yne (2) have been investigated and found to yield a mixture of products. From these, through the coupling of 2, the tetrasubstituted titanacyclopentadiene [Cp2Ti(CCH2PPh2)4] (3) was isolated. In addition, small amounts of very unusual complexes were obtained and characterized. In one case, the substrate 2 isomerized to the allene Ph2PC(H)=C=C(H)CH2PPh2, which formed the complex [Cp2Ti{η3‐Ph2PC(H)=C=C(H)CH2PPh2}] (4) through the coordination of a double bond and one of the phosphorus atoms. Another complex, [Cp2Ti{‐C(CH2PPh2)=C(CH2PPh2)P(Ph2)H‐}] (5), was identified to be the result of a formal hydrophosphorylation of the substrate 2 by HPPh2, and features a Ti–H–P bridge. It is not clear how HPPh2 was formed. One possible explanation is the dehydrophosphorylation of the substrate with the formation of HPPh2 and the butatriene H2C=C=C=C(H)PPh2 [tautomer of the but‐2‐en‐3‐yne HC≡C‐CH=C(H)PPh2]. The molecular structures of complexes 4 and 5 were determined by X‐ray analysis.
Organocatalytic Asymmetric Fluorination of 4‐Substituted Isoxazolinones
Authors: Zhang Huanrui , Wang Baomin , Cui Longchen , Bao Xiaoze , Qu Jingping , Song Yuming
Published: February 2015

A straightforward method for the asymmetric fluorination of 4‐substituted isoxazolinones catalyzed by a bis‐cinchona alkaloid catalyst was developed. A series of 4‐fluoroisoxazolinone derivatives with a fluorine‐containing quaternary stereocenter were obtained in good to high yields with good enantioselectivities (up to 91 % yield, 85 % ee).
Racemization of Olefinic Alcohols by a Carbonyl(cyclopentadienyl)ruthenium Complex: Inhibition by the Carbon–Carbon Double Bond
Authors: Warner Madeleine C. , Bäckvall Jan‐E.
Published: February 2015

In this article, racemization of various olefinic sec‐alcohols by Ru(CO)2(η5‐C5Ph5)Cl was investigated. The racemization of three aliphatic sec‐alcohols with different chain lengths containing terminal double bonds was studied. A dramatic decrease of the racemization rate was found for these sec‐alcohols compared to that of the corresponding saturated substrates. The slow racemization rate of the former alcohols is ascribed to coordination of the double bond to the ruthenium centre, which blocks the free site needed for β‐hydride elimination. This mechanism was supported by a recent study, in which 5‐hexen‐2‐ol was found to form an alkoxycarbonyl complex having the double bond coordinated to the ruthenium atom. Aliphatic sec‐alcohol substrates with a di‐ or trisubstituted double bond were found to give a lower degree of inhibition of the racemization rate than the substrates with a monosubstituted double bond.
Compartmented microfluidic bioreactor system using magnetic enzyme immobilisates for fast small‐scale biotransformation studies
Authors: Hübner Jonas , Brakowski Regina , Wohlgemuth Jonas , Brenner‐Weiß Gerald , Franzreb Matthias
Published: February 2015

In the last decade, microfluidic bioreactor systems became increasingly important due to their high suitability for lab‐on‐a‐chip applications and resource‐saving experiments with small sample volumes. Here, a prototype of a microfluidic device for fast small‐scale investigations of enzymatic and biochemical reactions is introduced. Single or consecutive enzyme‐catalyzed reactions can be implemented within compartmented reaction environments separated by immiscible fluidic plugs. By immobilizing one of the reactants onto magnetic microcarriers, a fast and easy separation of the reaction products is possible allowing the realization of a sequence of different reaction steps with different enzymes and varying chemical environments. Besides permanent magnetic fields for separation processes, alternating electromagnetic fields can be applied to resuspend the carriers. This leads to an intense mixing as well as even microcarrier distribution within the compartment. In a proof of concept, kinetic studies of HRP immobilized onto polyvinyl alcohol‐magnetite composite microcarriers are presented. The results showed a specific enzyme activity of approximately 89 units per gram immobilized biocatalyst under the applied reaction conditions. In addition, results of recycling experiments point out the importance of the magnetically induced resuspension. While ten times reuse with immobilisate resuspension resulted in substrate conversion yields between 95 and 65%, the same experiment without the magnetically induced resuspension showed conversion yields below 10% over all cycles.
Experimental study of vertically upward flame spread over polymethyl methacrylate slabs at different altitudes
Authors: Liang Canjun , Cheng Xudong , Yang Hui , Zhang Heping , Yuen Kwok Kit
Published: February 2015

Experiments of vertically upward flame spread over polymethyl methacrylate slabs were conducted in Hefei (with an altitude of 29.8 m) and Lhasa (with an altitude of 3658.0 m). Measurements were taken for the flame heights, the flame heat flux to the fuel surface and the flame spread rate. Two regions were identified for the dependence of the flame height on the heat release rate per unit width
. When
is less than 22 kW/m, the flame height scales as
while it scales as
, when
is greater than 22 kW/m. The flame heights in Lhasa are approximately 1.34 and 1.25 times, respectively, of those in Hefei for these two regions. The flame heat flux to the fuel surface decreases significantly from the pyrolysis front to the flame tip, whereas it decreases slowly above the flame tip. In both regions, it can be correlated reasonably well with (x − xp)/(xf − xp) using the form of
. The flame heat flux to the fuel surface in Lhasa is approximately 0.75 times of that in Hefei. The flame spread process can be divided into three stages, which correspond to a flow region of laminar, transitional, and turbulent, respectively. The transition to a turbulent flow is delayed in Lhasa compared with Hefei. The flame spread rate in Lhasa is about half of that in Hefei because of the lower flame heat flux caused by the lower ambient pressure. Copyright © 2015 John Wiley & Sons, Ltd.
Catalytic Influence of Oxide Component in Ni‐Based Cermet Anodes for Ammonia‐Fueled Solid Oxide Fuel Cells
Authors: Yang J. , Akagi T. , Okanishi T. , Muroyama H. , Matsui T. , Eguchi K.
Published: February 2015

Recently, the promising prospect of ammonia as a hydrogen carrier for solid oxide fuel cells (SOFCs) has attracted significant interests. In this work, the effects of temperature, fuel content, and total flow rate of anode gas on the performance of Ni/yttria‐stabilized zirconia (Ni/YSZ) anode for ammonia‐fueled SOFCs were investigated. Based on obtained results, the utilization route of ammonia on Ni/YSZ anode was discussed; the results of electrochemical experiments were related with the catalytic decomposition bahavior of ammonia over Ni/YSZ. Moreover, the catalytic activity for ammonia decomposition and anode performance of Ni/samarium‐doped ceria (Ni/SDC) and Ni/yttrium‐doped barium cerate (Ni/BCY) were also investigated. Among these anode materials, Ni/BCY exhibited the highest ammonia decomposition activity and anode performance for ammonia‐fueled SOFCs at intermediate temperatures.
Influence of the Temperature for the Ethanol Oxidation Reaction (EOR) on Pt/C, Pt‐Rh/C and Pt‐Rh‐SnO2/C
Authors: Bach Delpeuch A. , Asset T. , Chatenet M. , Cremers C.
Published: February 2015

The electrocatalytic activity of Pt/C, Pt‐Rh/C and Pt‐Rh‐SnO2/C electrocatalysts toward the ethanol oxidation reaction (EOR) was investigated in a three‐electrode assembly at 25 °C, 40 °C and 70 °C in acidic medium. The 10 wt.% electrocatalysts were prepared with a modified polyol method and physically characterized by both X‐Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). The CO‐stripping study revealed that COad oxidation initiates at lower potential on Pt‐Rh/C and Pt‐Rh‐SnO2/C than on Pt/C and shifts negatively when the temperature increases. The positive effect of the temperature is maintained for the EOR: the three electrocatalysts exhibit a higher activity and a negative shift of the EOR wave at higher temperature. Pt‐Rh‐SnO2/C demonstrates the lowest EOR onset potential of the three electrocatalysts. The steady‐state Tafel slopes and apparent activation energies Ea were determined in 0.5 M H2SO4 + 0.1 M EtOH between E = 0.4 and 0.7 V vs. RHE in the temperature range 25–70 °C. The results show rather comparable rate determining steps (rds) for the ethanol electrooxidation on Pt/C and Pt‐Rh/C in the ranges of potential and temperature studied. The EOR on Pt‐Rh‐SnO2/C seems less influenced by the potential than on Pt/C and Pt‐Rh/C electrocatalysts, but is more temperature sensitive.
Towards Comprehensive Description of Stack Durability/Reliability Behavior
Authors: Yokokawa H.
Published: February 2015

A new five‐year NEDO project on durability, on the basis of past two projects on SOFC durability/reliability, places an emphasis on simulation technologies to be utilized in comparison with measured long term stack behaviors and in prediction for 90,000 h durability. To extract true degradation issues, use is made of stack materials tested for a long term operation or for thermal cycles; to further confirm the mechanisms, use is made of single cells or button cells for specified issues. This makes it possible to correlate degradation behaviors of cell components with operational conditions such as temperature and oxygen potential with an aid of predetermination of microstructures of electrodes by FIB‐SEM or of the impurity levels inside major components at the beginning of cell operation. There are two major streams in such a comprehensive treatment of degradation; one is to predict the stack performance, the other being the prediction of mechanical instability. These will be described in details with special emphases on impurity effects and anomalous diffusion properties associated with respective extracted degradation issues.
Measuring vascular reactivity with breath‐holds after stroke: A method to aid interpretation of group‐level BOLD signal changes in longitudinal fMRI studies
Authors: Geranmayeh Fatemeh , Wise Richard J.S. , Leech Robert , Murphy Kevin
Published: February 2015

Blood oxygenation level‐dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath‐hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task‐related BOLD signal changes. Three methods of analyzing the breath‐hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri‐infarct tissue, both sub‐acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri‐infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group‐level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath‐hold‐based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. Hum Brain Mapp 36:1755–1771, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Effect of cloth stoma covers on tracheal climate of laryngectomy patients
Authors: Quail Gavin , Fagan Johannes J. , Raynham Oliver , Krynauw Hugo , John Lester Ryan , Carrara Henri
Published: February 2015

Background

The purpose of this study was to evaluate the efficacy of cloth stoma covers (bibs) to compensate for breathing unconditioned air after laryngectomy and loss of heat‐moisture‐exchange (HME) functions of the upper airways, which, to the best of our knowledge, has never been reported. In addition, we compared the efficacy of inexpensive, simple, locally made, noncommercial fabric bibs with commercial bibs and stick‐over‐the‐stoma HME devices and to determine whether wetting the bib improves the tracheal climate.

Methods

Tracheal temperature and humidity were studied in 25 patients who underwent a laryngectomy with a purpose‐built sampling device.

Results

Noncommercial and commercial bibs effectively heat and humidify inspired air (p < .05). Both bibs compare favorably with commercial HME devices. There is no benefit in using a commercially produced Buchanan Bib over an inexpensive noncommercial bib. Wetting a bib proved to be counterproductive.

Conclusion

Inexpensive, noncommercial bibs are effective and improve tracheal climate and benefit patients with laryngectomies. © 2015 Wiley Periodicals, Inc. Head Neck 38: E480–E487, 2016
The effect of Fe2O3 and ZnO nanoparticles on cytotoxicity and glucose metabolism in lung epithelial cells
Authors: Lai Xiaofeng , Wei Yifang , Zhao Hu , Chen Suning , Bu Xin , Lu Fan , Qu Dingding , Yao Libo , Zheng Jianyong , Zhang Jian
Published: February 2015

Metallic nanoparticles (NPs) have potential applications in industry and medicine, but they also have the potential to cause many chronic pulmonary diseases. Mechanisms for their cytotoxicity, glucose and energy metabolism responses need to be fully explained in lung epithelial cells after treatment with metallic nanoparticles. In our study, two different metallic nanoparticles (Fe2O3 and ZnO) and two cell‐based assays (BEAS‐2B and A549 cell lines) were used. Our findings demonstrate that ZnO nanoparticles, but not Fe2O3 nanoparticles, induce cell cycle arrest, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial dysfunction and glucose metabolism perturbation, which are responsible for cytotoxicity. These results also suggest that the glucose metabolism and bioenergetics had a great potential in evaluating the cytotoxicity and thus were very helpful in understanding their underlying molecular mechanisms. Copyright © 2015 John Wiley & Sons, Ltd.
Non‐clinical safety and biodistribution of AS03‐adjuvanted inactivated pandemic influenza vaccines
Authors: Segal Lawrence , Wouters Sandrine , Morelle Danielle , Gautier Gaëlle , Le Gal Julien , Martin Thomas , Kuper Frieke , Destexhe Eric , Didierlaurent Arnaud M. , Garçon Nathalie
Published: February 2015

Pandemic‐influenza vaccines containing split‐inactivated‐virus antigen have been formulated with the immunostimulatory Adjuvant System AS03 to enhance the antigen immunogenicity and reduce antigen content per dose. AS03 is an oil‐in‐water emulsion containing α‐tocopherol, squalene and polysorbate 80. To support the clinical development of AS03‐adjuvanted pandemic‐influenza vaccines, the local and systemic toxicity of test articles containing split‐influenza A(H5N1) and/or AS03 were evaluated after 3–4 intramuscular (i.m.) injections in rabbits. Treatment‐related effects were restricted to mild inflammatory responses and were induced primarily by the test articles containing AS03. The injection‐site inflammation was mild at 3 days, and minimal at 4 weeks after the last injection; and was reflected by signs of activation in the draining lymph nodes and by systemic effects in the blood including a transient increase of neutrophils. In addition, a study in mice explored the biodistribution of A(H5N1) vaccines or AS03 through radiolabelling the antigen or constituents of AS03 prior to injection. In this evaluation, 57–73% of AS03's principal constituents had cleared from the injection site 3 days after injection, and their different clearance kinetics were suggestive of AS03's dissociation. All these AS03 constituents entered into the draining lymph nodes within 30 min after injection. In conclusion, the administration of repeated doses of the H5N1/AS03 vaccine was well tolerated in the rabbit, and was primarily associated with transient mild inflammation at the injection site and draining lymph nodes. The biodistribution kinetics of AS03 constituents in the mouse were consistent with AS03 inducing this pattern of inflammation. Copyright © 2015 John Wiley & Sons, Ltd.