bluuebunny/crossref_metadata_2025 huggingface dataset:
Taste and Food in Rousseau’s Julie, or the New Heloise
Authors: Wertz S. K.
Published: July 2013

What are the historical origins of aesthetic education? One of these comes from the eighteenth century. This became an important theme in a novel of the time. In the midst of Julie and those who were close to her, Jean-Jacques Rousseau in his epistolary novel, Julie, or the New Heloise: Letters of Two Lovers who Live in a small Town at the Foot of the Alps (1761), develops a philosophical position he labels "the epicureanism of reason," as opposed to an epicureanism of the senses whose advocates he calls "vulgar epicureans." The hallmarks of his epicureanism are abstainment, moderation, and simplicity. These three features are examined and abstainment is found to be the most controversial in regard to taste. Rousseau attacks the food practices of the vulgar epicureans–those who practiced the urban, Parisian cuisine and he applauds the country life and its cuisine. Widely read at the time, the novel made European culture self-conscious and forced it to pay attention to aspects of living that had gone unnoticed or underappreciated, including taste and food. Through the voices of Julie and her tutor turned lover, Saint Preux, they provide a lively critique of French (and Swiss) society and its values.
Pinkster: An Atlantic Creole Festival in a Dutch-American Context
Authors: Dewulf Jeroen
Published: July 2013

This article argues that Pinkster should be understood as an Atlantic Creole festival in a Dutch-American context, rather than a Dutch-African festival in an American context. It claims that the syncretic character of Pinkster did not originate in North America and that, before arriving on the American East Coast, the essence of what came to be known as Pinkster already existed as a culturally hybrid Luso-African celebration.
Exact Solutions for Unsteady Magnetohydrodynamic Oscillatory Flow of a Maxwell Fluid in a Porous Medium
Authors: Khan Ilyas , Ali Farhad , Samiulhaq  , Shafie Sharidan
Published: July 2013

In this paper, exact solutions of velocity and stresses are obtained for the magnetohydrodynamic (MHD) flow of a Maxwell fluid in a porous half space by the Laplace transform method. The flows are caused by the cosine and sine oscillations of a plate. The derived steady and transient solutions satisfy the involved differential equations and the given conditions. Graphs for steady-state and transient velocities are plotted and discussed. It is found that for a large value of the time t, the transient solutions disappear, and the motion is described by the corresponding steady-state solutions.
An essential and NSF independent role for α-SNAP in store-operated calcium entry
Authors: Miao Yong , Miner Cathrine , Zhang Lei , Hanson Phyllis I , Dani Adish , Vig Monika
Published: July 2013

Store-operated calcium entry (SOCE) by calcium release activated calcium (CRAC) channels constitutes a primary route of calcium entry in most cells. Orai1 forms the pore subunit of CRAC channels and Stim1 is the endoplasmic reticulum (ER) resident Ca2+ sensor. Upon store-depletion, Stim1 translocates to domains of ER adjacent to the plasma membrane where it interacts with and clusters Orai1 hexamers to form the CRAC channel complex. Molecular steps enabling activation of SOCE via CRAC channel clusters remain incompletely defined. Here we identify an essential role of α-SNAP in mediating functional coupling of Stim1 and Orai1 molecules to activate SOCE. This role for α-SNAP is direct and independent of its known activity in NSF dependent SNARE complex disassembly. Importantly, Stim1-Orai1 clustering still occurs in the absence of α-SNAP but its inability to support SOCE reveals that a previously unsuspected molecular re-arrangement within CRAC channel clusters is necessary for SOCE.
Evaluating Radiation-induced White Matter Changes in Patients Treated with Stereotactic Radiosurgery Using Diffusion Tensor Imaging: A Pilot Study
Authors: Chang Zheng , Kirkpatrick John P. , Wang Zhiheng , Cai Jing , Adamson Justus , Yin Fang-Fang
Published: July 2013

Stereotactic radiosurgery (SRS) has been an effective treatment method for brain tumors; however, few data are available regarding radiation-induced white matter (WM) damage by SRS. In this work, diffusion tensor imaging (DTI) was used to investigate WM changes following SRS. Fifteen patients with gliomas were enrolled, with prescription doses ranging 18–25 Gy. Patients were scanned with magnetic resonance imaging (MRI) including DTI before and after SRS. Diffusion tensors were calculated and fiber tracking was performed. Non-irradiated WM volumes and irradiated WM volumes receiving ≥12 Gy and ≥5 Gy were contoured as volumes of interest (VOI). Apparent diffusion coefficient (), fractional anisotropy (FA) and number of fibers (NF) were calculated and assessed using the Wilcoxon signed-rank test. Compared with those of non-irradiated VOIs, FA and NF decreased considerably after two months of SRS in the irradiated WM VOIs. The variation in  was however small and was not statistically significant. The preliminary results suggested that FA and NF might potentially be more sensitive indicators than  in measuring radiation-induced WM changes and DTI could be a valuable tool to assess radiation-induced WM changes in SRS. Although it is still preliminary, this pilot study may be useful to provide insights for future studies.
Tissue Engineering Concept in the Research of the Tumor Biology
Authors: Xu Wen , Hu Xinlei , Pan Wensheng
Published: July 2013

Tumor is a heterogeneous complex, which lives in a three-dimensional environment flush with biopathophysiological and biomechanical signals. This signaling abundant extracellular milieu co-evolving from cell-cell and cell-host interaction guides the development and the generation of the tumor. There has been a recent surge of interest in studying the tumor biology that more closely mirror what happens in living organisms, especially in cancer research. Incorporating cancer cells in the 3D mimicking environment instead of monolayers is reasonable for maintaining in vivo cancer behaviors in spatial and temporal context. However, 3D culture for cancer still presents a challenge for researchers in this field. Tissue engineering, originally aiming at designing the artificial organs, provided a feasible approach to recreate such complex mechanical and biochemical interplay. Aside from reproducing bionic environment, tissue engineering has been routinely introduced into cancer study to build three dimensional structures not only to develop molecular therapeutics, but also to screen for toxic effects of drugs or radiotherapy sensitivity. In this article, we focused on the recent advances of the well-defined tissue-engineering biomaterials in the application in tumor biology. We also discussed the fabrications of the scaffolds from different materials, which might contribute to future cancer research.
Model Dynamic Pricinguntuk Penetapan Harga Tiket Pesawat Terbang Berbasis Waktu dan Persediaan Kursi dengan Mempertimbangkan Keputusan Kompetitor
Authors: Rusdiansyah Ahmad , Dwi A. P. Rescha , Puspitasari Nia
Published: July 2013

In the airline business nowadays the competition between airlinesis very tight. The decision of pricing of an airline will affect significantly the demand and revenue of other airlines. This study develops a model of Airline Revenue Management (ARM). We build an ARM model under competitive environment. The model considers the change of the competitor’s ticket for two parallel flights and should be made based on time and seat inventory. Specifically, we develop a model of dynamic programming to obtain the optimal ticket price based on the remaining seats, the rest of the time, as well as changes in competitors' ticket prices in order to generate maximum revenue expectation. This study conducted a series of numerical experiment scenarios to demonstrate the behavior of the model to the revenue expectation.
Curating NASA's Extraterrestrial Samples
Authors: Allen Carlton , Allton Judith , Lofgren Gary , Righter Kevin , Zeigler Ryan , Zolensky Michael
Published: July 2013

Curation of extraterrestrial samples is the critical interface between sample return missions and the international research community. Curation includes documentation, preservation, physical security, preparation, and allocation of samples for research, education, and public outreach.
Report Calls for U.S. National Sustainability Policy
Authors: Showstack Randy
Published: July 2013

The White House should issue an executive order establishing a U.S. national sustainability policy, according to a new report by a committee of the U.S. National Research Council (NRC) of the National Academies. The 28 June report found that sustainability issues inherently involve connections among environmental, economic, and social issues and that the U.S. federal government “is generally not organized or operated to deal with this complexity.” The report calls for a sustainability policy to address intertwined environmental, economic, and societal issues that require interagency cooperation.
Determining Scientific Projects for the Deep‐Sea Drilling Vessel Chikyu
Authors: Coffin Millard F. , Given Holly K. , Eguchi Nobuhisa
Published: July 2013

An international, multidisciplinary community workshop convened to define scientific projects for the next decade of scientific ocean drilling utilizing unique capabilities afforded by the drilling vessel Chikyu (“Earth” in Japanese). The meeting, attended by 397 participants from 21 countries, featured 10 keynote lectures. Participants in working groups identified important projects that are fundamental to understanding the Earth system and that require deep penetration of the seafloor.
Integrating Science, Management, and Policy for the Future of Water in California
Authors: Levy Michael
Published: July 2013

Society faces complex, multifaceted problems that call for research that transcends disciplinary boundaries and informs public policy. Water resources management in the face of climate change in California is one such challenge. Understanding responses to future conditions requires integration of climatic, hydrologic, ecological, and social dynamics. To catalyze the development and application of this science, the graduate students of the U.S. National Science Foundation–funded Climate Change, Water, and Society Integrative Graduate Education and Research Traineeship (CCWAS IGERT) at the University of California, Davis organized a “State of the Science” workshop to identify knowledge gaps; promote cross‐disciplinary communication, fertilization, and collaboration; and better connect science and policy.
Updates to Fall Meeting Abstract Submission and Social Events
Authors: McCarter‐Joseph Tricia
Published: July 2013

AGU has made important changes to the Fall Meeting abstract submissions policy and to two AGU events to be held during the 2013 Fall Meeting.
AGU Publications Continue to Rank High in 2012 Journal Citation Reports
Authors: Warner Mary
Published: July 2013

AGU journals continue to rank high in the 2012 Journal Citation Reports® (JCR), which was released by Thomson Reuters on 19 June. The impact factor of several AGU journals increased significantly, continuing their trend of the previous 5 years, while others remained consistent with the previous year's ranking.
New surface ocean current maps created from drifter data
Authors: Schultz Colin
Published: July 2013

The Global Drifter Program, which began in 1979 in the tropical Pacific Ocean, now spans the globe with a total of 1250 sensors. Tracked from orbit by satellites, the array provides a way to observe global near‐surface ocean circulation patterns.
The solar system has a bow shock after all—it is just slow
Authors: Schultz Colin
Published: July 2013

As our solar system travels through the Milky Way, the Sun's magnetic field interacts with the interstellar magnetic field and the interstellar medium, a mix of dust and gas that permeates interstellar space. At the edge of the heliosphere—the region of the solar system bounded by the Sun's magnetic field—the outflowing solar wind meets the interstellar medium to form the heliopause. On the far side of the heliopause the gas, dust, and cosmic rays of the interstellar medium slow down and pile up to form a structure known as a bow shock.
Can West African monsoon rainfall be predicted on decadal time scales?
Authors: Balcerak Ernie
Published: July 2013

The economies in much of West Africa are based on agriculture, which is strongly affected by rainfall variability. Thus, predictions of variations in West African monsoon rainfall could be valuable to people in those regions.
Estimated Frequency of Antiphospholipid Antibodies in Patients With Pregnancy Morbidity, Stroke, Myocardial Infarction, and Deep Vein Thrombosis: A Critical Review of the Literature
Authors: Andreoli Laura , Chighizola Cecilia B. , Banzato Alessandra , Pons‐Estel Guillermo J. , de Jesus Guilherme Ramire , Erkan Doruk ,   on behalf of APS ACTION
Published: July 2013

Objective

Antiphospholipid Syndrome Alliance For Clinical Trials and International Networking (APS ACTION) is an international research network devoted to conducting well‐designed clinical trials in persistently antiphospholipid antibody (aPL)–positive patients. One of the first needs of APS ACTION was to know the true aPL frequency in patients with pregnancy morbidity (PM), stroke (ST), myocardial infarction (MI), and deep venous thrombosis (DVT).

Methods

The search for “aPL” and multiple keywords regarding the outcomes of interest was completed in PubMed. The median frequency for positive aPL tests (lupus anticoagulant, antibody against cardiolipin [aCL], and antibody against β2‐glycoprotein I [anti‐β2GPI]) was calculated for each outcome and was used to estimate the overall aPL frequency.

Results

Based on the analysis of 120 full‐text papers, the overall aPL frequency was estimated as 6% for PM, 13.5% for ST, 11% for MI, and 9.5% for DVT. Limitations of the literature were that 60% of the papers were published before 2000, all 3 criteria aPL tests were performed in only 11% of the papers, 36% of papers used a low‐titer aCL cutoff, anti‐β2GPI cutoff was quite heterogeneous, aPL confirmation was performed in only one‐fifth of papers, and the study design was retrospective in nearly half of the papers.

Conclusion

It is difficult to determine the frequency of a “clinically significant aPL profile” in patients with aPL‐related clinical outcomes due to the lack of robust data. Our best estimates of the incidence of aPL‐associated events should be confirmed with appropriately designed population studies.
Clinical and Health Care Use Characteristics of Patients Newly Starting Allopurinol, Febuxostat, and Colchicine for the Treatment of Gout
Authors: Kim Seoyoung C. , Schmidt Bernhard M. W. , Franklin Jessica M. , Liu Jun , Solomon Daniel H. , Schneeweiss Sebastian
Published: July 2013

Objective

Gout is a common form of inflammatory arthritis with an increasing prevalence in developed countries. It is well known that many patients with gout have significant comorbidities and high health care utilization. We aimed to describe the clinical characteristics and health care utilization patterns in patients with gout who were newly prescribed allopurinol, febuxostat, or colchicine.

Methods

We used US insurance claims data (2009–2011) to conduct a population‐based cohort study.

Results

There were 25,051 allopurinol, 4,288 febuxostat, and 6,238 colchicine initiators. The mean age was 53 years and 83–87% were men. More than one‐half of the patients had hypertension and hyperlipidemia, 20% had diabetes mellitus, and 10% had cardiovascular disease. The mean uric acid level was similar across the groups at baseline, ranging from 8.1–8.5 mg/dl. Compared with allopurinol or colchicine initiators, febuxostat initiators had more comorbidities and greater health care utilization, including outpatient, inpatient, or emergency room visits, both at baseline and during followup. Use of gout‐related drugs such as opioids, steroids, and nonsteroidal antiinflammatory drugs was most common in febuxostat initiators and least common in colchicine initiators. The median daily doses at both the start and end of treatment were 300 mg for allopurinol, 40 mg for febuxostat, and 1.2 mg for colchicine. The doses of allopurinol and febuxostat were rarely increased during followup.

Conclusion

Patients who started allopurinol, febuxostat, or colchicine for gout generally had hyperuricemia and multiple comorbidities. Febuxostat initiators had more comorbidities and greater use of health care resources and gout‐related drugs than the other groups. Overall, the doses of allopurinol or febuxostat remained unchanged over time.
Quasi‐2D Colloidal Semiconductor Nanoplatelets for Narrow Electroluminescence
Authors: Chen Zhuoying , Nadal Brice , Mahler Benoit , Aubin Hervé , Dubertret Benoit
Published: July 2013

The first functional light‐emitting diodes (LEDs) based on quasi 2D colloidal core/shell CdSe/CdZnS nanoplatelets (NPLs). The solution‐processed hybrid devices are optimized with respect to their electroluminescent characteristics, first, by improving charge injection through exchanging the as‐synthesized NPL long‐chain ligands to shorter ones such as 3‐mercaptopropionic acid, and second, by comparing different hole‐transporting layers. NPL‐LEDs exhibit a maximum luminance of 4499 cd m‐2 and external quantum efficiencies of 0.63%. In particular, over different applied voltages, systematically narrow electroluminescence of full width at half maximum (FWHM) in the range of 25–30 nm is observed to be independent from the choice of device configuration and NPL ligands. As spectrally narrow electroluminescence is highly attractive in terms of color purity in the context of LED applications, these results emphasize the unique potential of this new class of colloidal core/shell nanoplatelet in achieving bright and functional LEDs of superior color purity.
High‐Efficiency Wet‐ and Dry‐Processed Green Organic Light Emitting Diodes with a Novel Iridium Complex‐Based Emitter
Authors: Jou Jwo‐Huei , Yang Yu‐Min , Chen Sun‐Zen , Tseng Jing‐Ru , Peng Shiang‐Hau , Hsieh Chun‐Yu , Lin You‐Xing , Chin Chih‐Lung , Shyue Jing‐Jong , Sun Shih‐Sheng , Chen Chien‐Tien , Wang Ching‐Wu , Chen Chien‐Chih , Lai Shih‐Hsiang , Tung Fu‐Ching
Published: July 2013

High efficiency green emission is crucial to the designs of energy‐saving display and lighting. Efficient electroluminescent green emitters with both wet‐ and dry‐process feasibility is highly desirable in order to realize, respectively, cost‐effective large roll‐to‐roll manufacturing and high performance products. In this study, high‐efficiency, phosphorescent, green organic light emitting diodes with a novel iridium complex, bis[5‐methyl‐8‐trifluoromethyl‐5H‐benzo(c)(1,5)naphthyridin‐6‐one] iridium (acetylacetonate), are demonstrated. They possess both wet‐ and dry‐processing possibilities. The emitter exhibits a short excited‐state lifetime, 1.25 μs, and a high quantum yield, 69%, due to the efficient intersystem crossing of the ground state to the excited state. Using 4,4′‐bis(carbazol‐9‐yl)biphenyl as a host, the device shows at 1000 cd m−2 an external quantum efficiency (EQE) of 21% and power efficiency of 64 lm W−1 via vapor deposition, while 26% EQE and 69 lm W−1 by spin‐coating, the highest among all reported wet‐processed green organic light emitting diodes. Besides electroluminescence, the high device efficiency may also be attributed to the employed device architecture enabling therein an electron trap to facilitate the injection of this minor carrier against that of a hole, leading to a balanced carrier‐injection, and hence a high carrier recombination and in turn a high device efficiency.
Stock Market Reactions to Contagious Animal Disease Outbreaks: An Event Study in Korean Foot‐and‐Mouth Disease Outbreaks
Authors: Pendell Dustin L. , Cho Chulgu
Published: July 2013

This study examines the market reactions by investors of Korean agribusiness companies following five foot‐and‐mouth disease (FMD) outbreaks using an event study analysis. The results suggest that the FMD outbreaks caused the stock market to react in both a negative and positive manner to allied companies. The results also suggest that the market reactions were more gradual than instantaneous to the FMD outbreaks. Furthermore, the FMD outbreaks appear to have increased the volatility of the daily returns with the smaller companies facing the largest changes in volatility.
Pain and other non‐neurological adverse events in children with sickle cell anemia and previous stroke who received hydroxyurea and phlebotomy or chronic transfusions and chelation: Results from the SWiTCH clinical trial
Authors: Alvarez Ofelia , Yovetich Nancy A. , Scott J. Paul , Owen William , Miller Scott T. , Schultz William , Lockhart Alexandre , Aygun Banu , Flanagan Jonathan , Bonner Melanie , Mueller Brigitta U. , Ware Russell E. ,   for the Investigators of the Stroke With Transfusions Changing to Hydroxyurea Clinical Trial (SWiTCH)
Published: July 2013

To compare the non‐neurological events in children with sickle cell anemia (SCA) and previous stroke enrolled in SWiTCH. The NHLBI‐sponsored Phase III multicenter randomized clinical trial stroke with transfusions changing to hydroxyurea (SWiTCH) (ClinicalTrials.gov NCT00122980) compared continuation of chronic blood transfusion/iron chelation to switching to hydroxyurea/phlebotomy for secondary stroke prevention and management of iron overload. All randomized children were included in the analysis (intention to treat). The Fisher's Exact test was used to compare the frequency of subjects who experienced at least one SCA‐related adverse event (AE) or serious adverse event (SAE) in each arm and to compare event rates. One hundred and thirty three subjects, mean age 13 ± 3.9 years (range 5.2–19.0 years) and mean time of 7 years on chronic transfusion at study entry, were randomized and treated. Numbers of subjects experiencing non‐neurological AEs were similar in the two treatment arms, including SCA‐related events, SCA pain events, and low rates of acute chest syndrome and infection. However, fewer children continuing transfusion/chelation experienced SAEs (P = 0.012), SCA‐related SAEs (P = 0.003), and SCA pain SAEs (P = 0.016) as compared to children on the hydroxyurea/phlebotomy arm. The timing of phlebotomy did not influence SAEs. Older age at baseline predicted having at least 1 SCA pain event. Patients with recurrent neurological events during SWiTCH were not more likely to experience pain. In children with SCA and prior stroke, monthly transfusions and daily iron chelation provided superior protection against acute vaso‐occlusive pain SAEs when compared to hydroxyurea and monthly phlebotomy. Am. J. Heamtol. 88:932–938, 2013. © 2013 Wiley Periodicals, Inc.
Generation of structural diversity in polyphosphazenes
Authors: Allcock Harry R.
Published: July 2013

Polyphosphazenes are macromolecules with a chain of alternating phosphorus and nitrogen atoms and with two (usually) organic side groups linked to each phosphorus. Although the earliest poly(organophosphazenes) were essentially linear polymers each bearing only one type of side group along the chain, research in our program in recent years has widened the scope to include mixed‐substituent polymers with two or more different side groups, block copolymers, comb structures, stars, and dendrimers, all with a wide variety of different properties. In addition, supramolecular systems have also been synthesized including vesicles, microspheres, and a variety of composite systems. This review provides a summary of these developments together with an introduction to the widening array of developing uses. Copyright © 2013 John Wiley & Sons, Ltd.
Synergistic effects of tetrabutyl titanate on intumescent flame‐retarded polypropylene
Authors: Zheng Anna , Xia Yin , Li Na , Mao Zongwen , Guan Yong
Published: July 2013

The synergistic mechanism of tetrabutyl titanate (TBT) in the intumescent flame‐retardant polypropylene (PP) composites was investigated in this work. The intumescent flame‐retardant was composed of pentaerythritol (PER) as a carbonizing agent ammonium polyphosphate (APP) as a dehydrating agent and blowing agent. Five different concentrations (1, 1.25, 1.5, 1.75, 2 wt %) of TBT were incorporated into flame retardant formulation to investigate the synergistic mechanism. The thermal degradation and flammability of composites were characterized by thermogravimetric analysis (TGA), limiting oxygen index (LOI), and UL‐94 tests. The morphology and chemical structure of char layer was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and energy dispersive spectrometer (EDS). The results showed that LOI was increased from 27.8 to 32.5%, with the increase of TBT content from 0 to 1.5 wt %. Results from SEM, and FTIR demonstrated that TBT could react with APP and PER to form the stable char layer. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 4255–4263, 2013
Biochemical and molecular mechanisms for the association between obesity, chronic Inflammation, and breast cancer
Authors: Rose David P. , Vona‐Davis Linda
Published: July 2013

Upper body obesity is a risk factor for postmenopausal breast cancer and is related to an aggressive tumor phenotype and a poor prognosis regardless of menopausal status. After the menopause, the major mechanism for the association with disease risk is elevated estrogen production by adipose tissue, due to a high level of aromatase activity: these hormone‐dependent tumors express both estrogen and progesterone receptors. Other important biological factors of risk include leptin and adiponectin, adipokines with opposing endocrine and paracrine activities, and obesity‐related hyperinsulinemia. Chronic inflammation of the breast adipose tissue, which occurs in some obese women and is indicated by the accumulation of macrophages around dead adipocytes (“crown‐like structures”), rather than adiposity per se, may prove to be the pathological lesion responsible for both local aromatase induction, and enhanced invasiveness and metastatic capacity through biological mechanisms that involve leptin, tumor necrosis factor‐α, and insulin. A causal association between obesity in premenopausal women and breast cell epithelial–mesenchymal transition, perhaps with the participation of the Wnt signaling pathway, and aggressive hormone‐independent breast cancer is suggested by a number of experimental and clinical studies. © 2013 BioFactors, 40(1):1–12, 2014
Quality by design approach for viral clearance by protein a chromatography
Authors: Zhang Min , Miesegaes George R. , Lee Michael , Coleman Daniel , Yang Bin , Trexler‐Schmidt Melody , Norling Lenore , Lester Philip , Brorson Kurt A. , Chen Qi
Published: July 2013

Protein A chromatography is widely used as a capture step in monoclonal antibody (mAb) purification processes. Antibodies and Fc fusion proteins can be efficiently purified from the majority of other complex components in harvested cell culture fluid (HCCF). Protein A chromatography is also capable of removing modest levels of viruses and is often validated for viral clearance. Historical data mining of Genentech and FDA/CDER databases systematically evaluated the removal of model viruses by Protein A chromatography. First, we found that for each model virus, removal by Protein A chromatography varies significantly across mAbs, while remains consistent within a specific mAb product, even across the acceptable ranges of the process parameters. In addition, our analysis revealed a correlation between retrovirus and parvovirus removal, with retrovirus data generally possessing a greater clearance factor. Finally, we describe a multivariate approach used to evaluate process parameter impacts on viral clearance, based on the levels of retrovirus‐like particles (RVLP) present among process characterization study samples. It was shown that RVLP removal by Protein A is robust, that is, parameter effects were not observed across the ranges tested. Robustness of RVLP removal by Protein A also correlates with that for other model viruses such as X‐MuLV, MMV, and SV40. The data supports that evaluating RVLP removal using process characterization study samples can establish multivariate acceptable ranges for virus removal by the protein A step for QbD. By measuring RVLP instead of a model retrovirus, it may alleviate some of the technical and economic challenges associated with performing large, design‐of‐experiment (DoE)—type virus spiking studies. This approach could also serve to provide useful insight when designing strategies to ensure viral safety in the manufacturing of a biopharmaceutical product. Biotechnol. Bioeng. 2014;111: 95–103. © 2013 The Authors.Biotechnology and BioengineeringPublished by Wiley Periodicals, Inc.
Non‐stationary 13C‐metabolic flux ratio analysis
Authors: Hörl Manuel , Schnidder Julian , Sauer Uwe , Zamboni Nicola
Published: July 2013

13C‐metabolic flux analysis (13C‐MFA) has become a key method for metabolic engineering and systems biology. In the most common methodology, fluxes are calculated by global isotopomer balancing and iterative fitting to stationary 13C‐labeling data. This approach requires a closed carbon balance, long‐lasting metabolic steady state, and the detection of 13C‐patterns in a large number of metabolites. These restrictions mostly reduced the application of 13C‐MFA to the central carbon metabolism of well‐studied model organisms grown in minimal media with a single carbon source. Here we introduce non‐stationary 13C‐metabolic flux ratio analysis as a novel method for 13C‐MFA to allow estimating local, relative fluxes from ultra‐short 13C‐labeling experiments and without the need for global isotopomer balancing. The approach relies on the acquisition of non‐stationary 13C‐labeling data exclusively for metabolites in the proximity of a node of converging fluxes and a local parameter estimation with a system of ordinary differential equations. We developed a generalized workflow that takes into account reaction types and the availability of mass spectrometric data on molecular ions or fragments for data processing, modeling, parameter and error estimation. We demonstrated the approach by analyzing three key nodes of converging fluxes in central metabolism of Bacillus subtilis. We obtained flux estimates that are in agreement with published results obtained from steady state experiments, but reduced the duration of the necessary 13C‐labeling experiment to less than a minute. These results show that our strategy enables to formally estimate relative pathway fluxes on extremely short time scale, neglecting cellular carbon balancing. Hence this approach paves the road to targeted 13C‐MFA in dynamic systems with multiple carbon sources and towards rich media. Biotechnol. Bioeng. 2013;110: 3164–3176. © 2013 Wiley Periodicals, Inc.
Determination of chidamide in rat plasma by LC‐MS and its application to pharmacokinetics study
Authors: Wang Xianqin , Chen Mengchun , Wen Congcong , Zhang Qingwei , Ma Jianshe
Published: July 2013

A sensitive and selective liquid chromatography mass spectrometry method for determination of chidamide in rat plasma was developed. After addition of linezolid as internal standard, protein precipitation by acetonitrile–methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB‐C18 (2.1 × 150 mm, 5 µm) column with acetonitrile–0.1% formic acid as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification using target fragment ions m/z 391.5 for chidamide and m/z 338.5 for the IS. Calibration plots were linear over the range of 10–2000 ng/mL for chidamide in rat plasma. The lower limit of quantification for chidamide was 10 ng/mL. The mean recovery of chidamide in plasma was in the range of 86.6–92.1%. The coefficients of variation of intra‐day and inter‐day precision were both <12%. This method is simple and sensitive and was applied successfully in a pharmacokinetic study of chidamide to rats. Copyright © 2013 John Wiley & Sons, Ltd.
Tuning Excited State Isomerization Dynamics through Ground State Structural Changes in Analogous Ruthenium and Osmium Sulfoxide Complexes
Authors: Garg Komal , Engle James T. , Ziegler Christopher J. , Rack Jeffrey J.
Published: July 2013

The complexes [Ru(bpy)2(pyESO)](PF6)2 and [Os(bpy)2(pyESO)](PF6)2, in which bpy is 2,2′‐bipyridine and pyESO is 2‐((isopropylsulfinyl)ethyl)pyridine, were prepared and studied by 1H NMR, UV–visible and ultrafast transient absorption spectroscopy, as well as by electrochemical methods. Crystals suitable for X‐ray structural analysis were grown for [Ru(bpy)2(pyESO)](PF6)2. Cyclic voltammograms of both complexes provide evidence for S→O and O→S isomerization as these voltammograms are described by an ECEC (electrochemical‐chemical electrochemical‐chemical) mechanism in which isomerization follows Ru2+ oxidation and Ru3+ reduction. The S‐ and O‐bonded Ru3+/2+ couples appear at 1.30 and 0.76 V versus Ag/AgCl in propylene carbonate. For [Os(bpy)2(pyESO)](PF6)2, these couples appear at 0.97 and 0.32 V versus Ag/AgCl in acetonitrile, respectively. Charge‐transfer excitation of [Ru(bpy)2(pyESO)](PF6)2 results in a significant change in the absorption spectrum. The S‐bonded isomer of [Ru(bpy)2(pyESO)]2+ features a lowest energy absorption maximum at 390 nm and the O‐bonded isomer absorbs at 480 nm. The quantum yield of isomerization in [Ru(bpy)2(pyESO)]2+ was found to be 0.58 in propylene carbonate and 0.86 in dichloroethane solution. Femtosecond transient absorption spectroscopic measurements were collected for both complexes, revealing time constants of isomerizations of 81 ps (propylene carbonate) and 47 ps (dichloroethane) in [Ru(bpy)2(pyESO)]2+. These data and a model for the isomerizing complex are presented. A striking conclusion from this analysis is that expansion of the chelate ring by a single methylene leads to an increase in the isomerization time constant by nearly two orders of magnitude.
Study of the Enantioselective Interaction of Diclofop and Human Serum Albumin by Spectroscopic and Molecular Modeling Approaches In Vitro
Authors: Zhang Ping , Li Zhe , Wang Xinru , Shen Zhigang , Wang Yao , Yan Jin , Zhou Zhiqiang , Zhu Wentao
Published: July 2013

In this contribution, the enantioselective interactions between diclofop (DC) and human serum albumin (HSA) were explored by steady‐state and 3D fluorescence, ultraviolet‐visible spectroscopy (UV‐vis), and molecular modeling. The binding constants between R‐DC and HSA were 0.9213 × 105, 0.9118 × 105, and 0.9009 × 105 L · mol‐1 at 293, 303, 313 K, respectively. Moreover, the binding constants of S‐DC for HSA were 1.4766 × 105, 1.2899 × 105, and 1.0882 × 105 L · mol‐1 at 293, 303, and 313 K individually. Such consequences markedly implied the binding between DC enantiomers and HSA were enantioselective with higher affinity for S‐DC. Steady‐state fluorescence study evidenced the formation of DC‐HSA complex and there was a single class of binding site on HSA. The thermodynamic parameters (ΔH, ΔS, ΔG) of the reaction clearly indicated that hydrophobic effects and H‐bonds contribute to the formation of DC‐HSA complex, which was in excellent agreement with molecular simulations. In addition, both site‐competitive replacement and molecular modeling suggested that DC enantiomers were located within the binding pocket of Sudlow's site II. Furthermore, the alterations of HSA secondary structure in the presence of DC enantiomers were verified by UV‐vis absorption and 3D fluorescence spectroscopy. This study can provide important insight into the enantioselective interaction of physiological protein HSA with chiral aryloxyphenoxy propionate herbicides and gives support to the use of HSA for chiral pesticides ecotoxicology and environmental risk assessment. Chirality 25:719–725, 2013. © 2013 Wiley Periodicals, Inc.
Long‐term prognosis and risk factors among patients with HPV‐associated oropharyngeal squamous cell carcinoma
Authors: Lin Brian M. , Wang Hao , D'Souza Gypsyamber , Zhang Zhe , Fakhry Carole , Joseph Andrew W. , Drake Virginia E. , Sanguineti Giuseppe , Westra William H. , Pai Sara I.
Published: July 2013

BACKGROUND

A subset of patients with human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (HPV‐OSCC) experience poor clinical outcomes. The authors of this report explored prognostic risk factors for overall survival (OS) and recurrence‐free survival (RFS).

METHODS

Patients with incident HPV‐OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing as well as demographic and clinicopathologic information (N = 176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and clinicopathologic information was extracted from medical records.

RESULTS

In total, 157 of 176 patients (90%) with OSCC had HPV‐associated disease (HPV‐OSCC). In the patients with HPV‐OSCC, the 3‐year and 5‐year OS rates were 93% (95% confidence interval [CI], 88%‐98%) and 89% (95% CI, 81%‐97%), respectively. Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per 10‐year increase; 95% CI, 1.05‐5.16 per 10‐year increase; P = .038), patients with advanced clinical T classification (HR, 5.78; 95% CI, 1.60‐20.8; P = .007), and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07‐18.0; P = .04). Disease recurrence was associated with advanced clinical T‐classification (HR, 8.32; 95% CI, 3.06‐23; P < .0001), current/former alcohol use (HR, 13; 95% CI, 1.33‐120; P = .03), and unmarried status (HR, 3.28; 95% CI, 1.20‐9.00; P = .02). Patients who remained recurrence free for 5 years had an 8.6% chance of recurrence by 10 years (1‐sided 95% CI upper bound, 19%; P = .088).

CONCLUSIONS

In this study, prognostic risk factors were identified for patients with HPV‐OSCC. The observed recurrence rates between 5 years and 10 years after definitive therapy need to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462–3471.. © 2013 American Cancer Society.
Impact of hemochromatosis gene mutations on cardiac status in doxorubicin‐treated survivors of childhood high‐risk leukemia
Authors: Lipshultz Steven E. , Lipsitz Stuart R. , Kutok Jeffery L. , Miller Tracie L. , Colan Steven D. , Neuberg Donna S. , Stevenson Kristen E. , Fleming Mark D. , Sallan Stephen E. , Franco Vivian I. , Henkel Jacqueline M. , Asselin Barbara L. , Athale Uma H. , Clavell Luis A. , Michon Bruno , Laverdiere Caroline , Larsen Eric , Kelly Kara M. , Silverman Lewis B.
Published: July 2013

BACKGROUND

Doxorubicin is associated with progressive cardiac dysfunction, possibly through the formation of doxorubicin‐iron complexes leading to free‐radical injury. The authors determined the frequency of hemochromatosis (HFE) gene mutations associated with hereditary hemochromatosis and their relationship with doxorubicin‐associated cardiotoxicity in survivors of childhood high‐risk acute lymphoblastic leukemia.

METHODS

Peripheral blood was tested for 2 common HFE allelic variants: C282Y and H63D. Serum cardiac troponin‐T (cTnT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), which are biomarkers of cardiac injury and cardiomyopathy, respectively, were assayed during therapy. Left ventricular (LV) structure and function were assessed with echocardiography.

RESULTS

A total of 184 patients had DNA results for at least 1 variant, and 167 had DNA results for both: 24% carried H63D and 10% carried C282Y. Heterozygous C282Y genotype was associated with multiple elevations in cTnT concentrations (P = .039), but not NT‐proBNP. At a median of 2.2 years (range, 1.0 years–3.6 years) after diagnosis, the mean Z‐scores for LV fractional shortening (−0.71 [standard error (SE), 0.25]; P = .008), mass (−0.84 [SE, 0.17]; P < .001), and end‐systolic (−4.36 [SE, 0.26], P < .001) and end‐diastolic (−0.68 [SE, 0.25]; P = .01) posterior wall thickness were found to be abnormal in children with either allele (n = 32). Noncarriers (n = 63) also were found to have below‐normal LV mass (−0.45 [SE, 0.15]; P = .006) and end‐systolic posterior wall thickness (−4.06 [SE, 0.17]; P < .001). Later follow‐up demonstrated similar results.

CONCLUSIONS

Doxorubicin‐associated myocardial injury was associated with C282Y HFE carriers. Although LV mass and wall thickness were found to be abnormally low overall, they were even lower in HFE carriers, who also had reduced LV function. Screening newly diagnosed cancer patients for HFE mutations may identify those at risk for doxorubicin‐induced cardiotoxicity. Cancer 2013;119:3555–3562.. © 2013 American Cancer Society.
Si⋅⋅⋅H Interligand Interactions in Cobalt(V) and Iridium(V) Bis(silyl)bis(hydride) Complexes
Authors: Horbatenko Yevhen , Vyboishchikov Sergei F.
Published: July 2013

A series of bis(silyl)bis(hydride) cobalt complexes [Cp*Co(H)2(SiR3)2] (Cp*=pentamethylcyclopentadienyl; SiR3=SiPh2H, SiMe3, SiH3, SiF3, SiCl3, SiBr3, Si(CF3)3; Co1–Co7) as well as the analogous iridium complexes [Cp*Ir(H)2(SiR3)2] (SiR3=SiEt3, SiMe3, SiH3, SiF3, SiCl3, SiBr3, Si(CF3)3; Ir1–Ir7) were studied to detect possible residual Si⋅⋅⋅H interactions. Tests of several density functionals by comparison with coupled‐cluster results indicate that the TPSSh functional performs better than B3LYP, BP86, M06, M06L, and PBEPBE. Based on molecular structures, as well as Wiberg bond indices and J(Si,H) spin–spin coupling constants as indicators of a possible Si⋅⋅⋅H interaction, at least two residual Si⋅⋅⋅H interactions in Co2, Co5, and all four possible Si⋅⋅⋅H interactions in Co3 and Co4 have been detected. Co6 and Co7 exhibit stronger Si⋅⋅⋅H bonding than the other complexes studied. On the contrary, the iridium complexes Ir1–Ir3 and Ir5–Ir7 are classical iridium(V) bis(silyl)bis(hydride) complexes with only rudimentary Si⋅⋅⋅H interactions, if any.
Cogging Torque Characteristics of a Magnetic‐Geared Motor
Authors: Niguchi Noboru , Hirata Katsuhiro
Published: July 2013

This paper describes the cogging torque characteristics of a magnetic‐geared motor with permanent magnets only on the high‐speed rotor. The operational principle, which is different from that of the magnetic‐geared motor with permanent magnets on the high‐speed rotor and stator, is described. The torque characteristics, especially the order of the cogging torque, are mathematically formulated and verified by conducting 3D finite element analysis and carrying out measurements on a prototype. A novel cogging torque reduction method is proposed and verified as well.
Effect of Hydrogen and Oxygen Evolution Cocatalysts on Photocatalytic Activity of GaN:ZnO
Authors: Xiong Anke , Yoshinaga Taizo , Ikeda Takahiro , Takashima Masaki , Hisatomi Takashi , Maeda Kazuhiko , Setoyama Toru , Teranishi Toshiharu , Domen Kazunari
Published: July 2013

The coloading effect of H2 and O2 evolution cocatalysts on the overall water splitting reaction was investigated using a solid solution of GaN and ZnO (hereafter termed GaN:ZnO) as a photocatalyst. GaN:ZnO was modified with nanoparticulate Mn3O4, RuO2, and IrO2 as O2 evolution cocatalysts and with core/shell‐type Rh/Cr2O3 composites as H2 evolution cocatalysts. The photocatalytic activity of the coloaded samples for overall water splitting was higher than that of the samples modified with either of the O2 or H2 evolution cocatalysts alone. The activity enhancement induced by coloading was comparable for the three O2 evolution cocatalysts investigated at the optimized loading amounts. Loading of a more efficient Rh/Cr2O3 cocatalyst prepared by adsorption of Rh nanoparticles further improved the photocatalytic activity. It was concluded that a simultaneous improvement in both oxidation and reduction reactions was effective at enhancing the photocatalytic activity of GaN:ZnO, whereas the reduction reactions limited the overall reaction rate of the coloaded system more significantly.
Direct Amidation of Amino Acid Derivatives Catalyzed by Arylboronic Acids: Applications in Dipeptide Synthesis
Authors: Liu Shouxin , Yang Yihua , Liu Xinwei , Ferdousi Farhana K. , Batsanov Andrei S. , Whiting Andrew
Published: July 2013

The direct amidation of amino acid derivatives catalyzed by arylboronic acids has been examined. The reaction was generally slow relative to simple amine‐carboxylic acid combinations though proceeded at 65–68 °C generally avoiding racemization. 3,4,5‐Trifluorophenylboronic and o‐nitrophenylboronic acids were found to be the best catalysts, though for slower dipeptide formations, high catalyst loadings were required and an interesting synergistic catalytic effect between two arylboronic acids was discovered.
Application of capillary electrophoretic chips in protein profiling of plant extracts for identification of genetic modifications of maize
Authors: Poboży Ewa , Filaber Monika , Koc Anna , Garcia‐Reyes Juan F.
Published: July 2013

In this study, the chip gel electrophoresis with LIF detection was applied in protein profiling of fractionated and total extracts of maize standards. The sensitivity of such determinations can be enhanced by lyophilization of extracts or employing filtering and preconcentration with cutoff filters. Combinatorial peptide ligand library applied for sample processing prior to the electrophoretic analysis was, especially, an effective pretreatment step in the determination of low‐abundance proteins. Several repeatable differences were observed for protein profiles between maize standards not containing the genetically modified organisms (GMOs) and those containing GMO, which can be potentially employed for identification of GMO in maize samples and foods of maize origin.
Distinct metabolic differences between various human cancer and primary cells
Authors: Dettmer Katja , Vogl Franziska C. , Ritter Axel P. , Zhu Wentao , Nürnberger Nadine , Kreutz Marina , Oefner Peter J. , Gronwald Wolfram , Gottfried Eva
Published: July 2013

Recent years have seen resurging interest in cancer cell metabolism and the role of secreted cancer metabolites in modulating the tumor stroma. Using a combination of nontargeted and targeted LC and GC‐MS methods, the exometabolomes of three leukemia, two melanoma, three renal cell carcinoma, two colorectal adenocarcinoma, four hepatocellular carcinoma, three breast cancer, two bladder carcinoma, and one glioblastoma cell line, as well as five primary cultures of human melanocytes, hepatocytes, monocytes, CD4 and CD8 lymphocytes, that had been all cultivated under identical conditions, were investigated. Unsupervised affinity propagation clustering of the metabolic footprints yielded five distinct clusters that grouped the investigated cell cultures mainly according to the tissue of origin. A common expected feature of all neoplastic cells was high lactate production. Extracellular arginine and nicotinamide were major discriminants between normal and neoplastic hepatocytes. Further, significant differences in the assimilation of di‐ and tripeptides were observed. This finding appears to underscore the importance of peptides for meeting the increased bioenergetic and biosynthetic demands of many cancers.