bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optoacoustic Imaging and Staging of Inflammation in a Murine Model of Arthritis
Authors: Beziere N. , von Schacky C. , Kosanke Y. , Kimm M. , Nunes A. , Licha K. , Aichler M. , Walch A. , Rummeny E. J. , Ntziachristos V. , Meier R. 
Published: April 2014

ObjectiveRheumatoid arthritis (RA) is one of the most frequent inflammatory diseases, causing pain and disability in the affected joints. Early diagnosis is essential for the efficiency of symptom‐targeting treatments, but its diagnosis requires careful clinical, serologic, and imaging examinations, such as magnetic resonance imaging (MRI), which is both expensive and time consuming. In an effort to provide the biomedical community with a more accessible way to assess the advancement of arthritis, this study sought to investigate the use of multispectral optoacoustic tomography (MSOT) in a murine arthritis model, to visualize the extent of inflammation in vivo through an L‐selectin/P‐selectin–targeting contrast agent.MethodsMice with collagen‐induced arthritis were studied as a model of RA. MSOT was performed using an L‐selectin/P‐selectin–targeting contrast agent, polyanionic dendritic polyglycerol sulfate (dPGS) labeled with a near‐infrared (NIR) fluorophore, to increase the contrast of the arthritic joint. The signal intensity ratios between healthy legs and arthritic legs were calculated. Findings on contrast‐enhanced MRI, clinical observations, the lymphocyte:granulocyte ratio, and histologic findings served as referents for comparison.ResultsMSOT using an inflammation‐targeting contrast agent, dPGS‐NIR, allowed for accurate diagnosis of inflammation in the mouse joints. In addition, use of this technique resulted in significant differentiation of the inflamed joints from the healthy joints (P = 0.023). The observed advancement of arthritis on the MSOT images was confirmed by clinical observation, blood analysis, contrast‐enhanced MRI, and ex vivo histologic examinations.ConclusionThis study demonstrates that the combination of an inflammation‐targeting contrast agent and optoacoustic tomographic imaging presents a promising means for the diagnosis of RA and the staging of arthritis‐related inflammation.
BIM – Erfahrungen bei der Anwendung einer neuen Methode im Ingenieurbüro
Authors: Mansperger Tobias , Jung Rolf , Thiele Tobias , Steinberg Andrea 
Published: April 2014

AbstractDas Ingenieurbüro Leonhardt, Andrä und Partner konnte in den letzten Jahren weitreichende Erfahrungen mit der Anwendung von Building Information Modeling (BIM) sammeln. Dabei wurde nicht nur in der Praxis BIM der ersten und zweiten Stufe angewandt, sondern auch im Zuge von Forschungsprojekten an der Weiterentwicklung der Methode auf höheren Ebenen gearbeitet.Bei der praktischen Anwendung kommen zurzeit hauptsächlich geschlossene Methoden, also mit einer speziellen Software bzw. Partnersoftware und deren spezifischer Schnittstelle zum Einsatz. Bereits bei dieser sog. ersten Stufe von BIM ergeben sich auch schon in frühen Projektphasen zahlreiche Vorteile, die dessen Einsatz lohnenswert machen. Bei der Anwendung der offenen Methode mit Datenaustausch via IFC wurde wiederholt deutlich, dass die Funktionalitäten der beteiligten Software dadurch eingeschränkt werden, dass bestimmte Modellparameter nicht ausgetauscht werden können oder die Schnittstellen noch fehlerbehaftet sind.Bei der Beteiligung an Forschungsprojekten wird ersichtlich, welche weitreichenden Chancen open BIM bietet, aber auch welche technischen Hürden zu überwinden sind. Durch die Weiterentwicklung der Schnittstellen sowie die Verwendung von Cloud bzw. Grid Computing werden hochkomplexe und rechenaufwändige Analysen der Bauwerke ermöglicht. Webbasierte Plattformen erlauben effizientes Zusammenarbeiten verschiedener Fachdisziplinen sowie ein optimiertes Zusammenspiel unterschiedlichster Analysesoftware.BIM – Experiences of the application of a new method in an engineering companyConsulting engineers Leonhardt Andrä and Partners were able to gather extensive experiences in the application of BIM. Not only first and second level BIM was used in practice, but also by contributing to research projects, the method was developed on higher levels.At daily practice, mainly closed BIMs are worked on by using proprietary software with a specific interface. Already on this first level BIM, many advantages are becoming obvious that also pay off on early project stages. It became apparent, that the application of open BIM with data exchange via IFC limits the functionalities of the participating software, as some model parameters can't be exchanged, or interfaces are defective.The participation in research projects shows on the one hand the chances of open BIM, on the other hand what problems have to be resolved. By developing the interfaces and Cloud/Grid computing, highly complex and computing time consuming analyses are made feasible. Web‐based platforms allow efficient co‐working of different disciplines and an optimized cooperation of different tools.
4‐O‐methylhonokiol Inhibits Serious Embryo Anomalies Caused by Nicotine via Modulations of Oxidative Stress, Apoptosis, and Inflammation
Authors: Lin Chunmei , Yon Jung‐Min , Hong Jin Tae , Lee Jong Kwon , Jeong Jayoung , Baek In‐Jeoung , Lee Beom Jun , Yun Young Won , Nam Sang‐Yoon 
Published: April 2014

BACKGROUNDSince the increasing smoking rate among women has resulted in higher rates of embryonic malformations, it is important to search for an efficient and inexpensive agent that can help reduce the rate of serious fetal anomalies caused by maternal cigarette smoking. In this study, the bioavailability of 4‐O‐methylhonokiol isolated from Magnolia officinalis was first demonstrated in the mouse embryos exposed to nicotine using a whole embryo culture system.METHODSMouse embryos on embryonic day 8.5 were cultured with 1 mM nicotine and/or 4‐O‐methylhonokiol (1 × 10−4 or 1 × 10−3 μM) for 48 hr and were analyzed on the viewpoints of embryo developmental changes, oxidative damages, and apoptotic and inflammatory changes.RESULTSEmbryos exposed to 1 mM nicotine developed not only severe morphological anomalies, increased expressions of tumor necrosis factor‐α, interleukin‐1β, and caspase 3 mRNAs; and elevated levels of lipid peroxidation, but also decreased levels of cytoplasmic superoxide dismutase, cytosolic glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, hypoxia inducible factor‐1α, and B‐cell lymphoma‐extra large mRNAs, and reduced superoxide dismutase activity. However, these parameters were significantly improved when embryos exposed to the nicotine were concurrently treated with 4‐O‐methylhonokiol (1 × 10−4 or 1 × 10−3 μM).CONCLUSIONSThese findings indicate that 4‐O‐methylhonokiol reduces serious embryo anomalies caused by nicotine in mouse embryos via the modulations of oxidative stress, apoptosis, and inflammation, suggesting that 4‐O‐methylhonokiol may be a preventive and therapeutic agent against the dysmorphology induced by maternal smoking during pregnancy.
Absence of Irreversible Effects of Aliskiren in Standard Juvenile Rat Toxicity Studies
Authors: Beckman David , Barbeau Stephanie , McLean Lee Anne , Yan Jing‐He , Hoffmann Peter 
Published: April 2014

BACKGROUNDAliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension in adults. Juvenile toxicity studies in rats were initiated to support treatment in the pediatric population.METHODSIn Study 1, aliskiren oral administration was initiated on postpartum day (PPD) 14, after nephrogenesis was completed, and continued through PPD 70 at doses of 0, 30, 100, and 300 mg/kg/day. In‐life, clinical pathology, anatomic pathology, developmental, behavioral, reproductive, and toxicokinetics evaluations were performed. In Study 2, oral administration was initiated on PPD 8, before completion of nephrogenesis, and continued through PPD 35/36. In‐life, clinical pathology, anatomic pathology, developmental, and toxicokinetics evaluations were performed.RESULTSWith dosing initiated on PPD 8, mortality at 100 and 300 mg/kg/day and slightly increased kidney weight at 100 mg/kg/day occurred. Decreased absolute lymphocyte count at 300 mg/kg/day at the end of dosing occurred with dosing initiated on PPD 14. There were clinical signs and transient effects on body weight gains in both studies. There were no changes in other parameters. Systemic exposure was much higher on PPD 8 and 14 compared with adult rats on PPD 64.CONCLUSIONSAll effects produced by aliskiren, including kidney effects, were reversible. Increased exposure in very young animals is considered to be the result of immature drug transporter systems.
Biochemical Investigations of Two 6‐DMATS Enzymes from Streptomyces Reveal New Features of L‐Tryptophan Prenyltransferases
Authors: Winkelblech Julia , Li Shu‐Ming 
Published: April 2014

AbstractTwo putative prenyltransferase genes, SAML0654 and Strvi8510, were identified in Streptomyces ambofaciens and Streptomyces violaceusniger, respectively. Their deduced products share 63 % sequence identity. Biochemical investigations with recombinant proteins demonstrated that L‐tryptophan and derivatives, including D‐tryptophan, 4‐, 5‐, 6‐ and 7‐methyl‐dl‐tryptophan, were well accepted by both enzymes in the presence of DMAPP. Structural elucidation of the isolated products revealed regiospecific prenylation at C‐6 of the indole ring and proved unequivocally the identification of two very similar 6‐dimethylallyltryptophan synthases (6‐DMATS). Detailed biochemical investigations with SAML0654 proved L‐tryptophan to be the best substrate (Km 18 μm, turnover 0.3 s−1). Incubation with different prenyl donors showed that they also accepted GPP and catalyzed the same specific prenylation. Utilizing GPP as a prenyl donor has not been reported for tryptophan prenyltransferases previously. Both enzymes also catalyzed prenylation of some hydroxynaphthalenes; this has not previously been described for bacterial indole prenyltransferases. Interestingly, SAML0654 transferred prenyl moieties onto the unsubstituted ring of hydroxynaphthalenes.
Mukaiyama–Michael Reactions with trans‐2,5‐Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions, Not from Steric Hindrance
Authors: Kemppainen Eeva K. , Sahoo Gokarneswar , Piisola Antti , Hamza Andrea , Kótai Bianka , Pápai Imre , Pihko Petri M. 
Published: April 2014

AbstractThe scope of the enantioselective Mukaiyama–Michael reactions catalyzed by trans‐2,5‐diphenylpyrrolidine has been expanded to include both α‐ and β‐substituted enals. However, the rationalization of the observed enantioselectivity is far from obvious since the catalyst is not very sterically hindered. DFT calculations were carried out to rationalize the observed stereoselectivities. Transition states of the CC bond formation between iminium intermediates and silyloxyfurans were located and their relative energies were used to estimate the stereoselectivity data. We find excellent agreement between the predicted and observed stereoselectivities. The analysis of intermolecular forces reveals that the enantioselectivity is mostly due to stabilizing noncovalent interactions between the reacting partners, not due to steric hindrance. The role of attractive noncovalent interactions in enantioselective catalysis may be underappreciated.
Development of Fluorescent Film Sensors Based on Electropolymerization for Iron(III) Ion Detection
Authors: Li Peng , Ji Changyin , Ma Hongwei , Zhang Ming , Cheng Yunfei 
Published: April 2014

AbstractTwo electroactive materials, M1 and M2, are synthesized and their fluorescent electropolymerized (EP) films are prepared and used to detect metal ions. From the tested metal ions, M1 and M2 are demonstrated to be sensitive and selective for Fe3+ ions. In particular, M2 exhibits higher sensitivity towards Fe3+ ions. The fluorescent detection ranges from 10−5 M to 4×10−4 M. The excellent performance of the EP fluorescent films is mainly due to the strong metal‐chelated properties of M2 and the intrinsic porous cross‐linked‐network microstructure of the EP films. This study, thus, provides a promising Fe3+ sensing candidate and a potential preparation method for fluorescent sensing films.
Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin–Gold Nanoparticles
Authors: Palmal Sharbari , Maity Amit Ranjan , Singh Brijesh Kumar , Basu Sreetama , Jana Nihar R. , Jana Nikhil R. 
Published: April 2014

AbstractInhibition of amyloid fibrillation and clearance of amyloid fibrils/plaques are essential for the prevention and treatment of various neurodegenerative disorders involving protein aggregation. Herein, we report curcumin‐functionalized gold nanoparticles (Au‐curcumin) of hydrodynamic diameter 10–25 nm, which serve to inhibit amyloid fibrillation and disintegrate/dissolve amyloid fibrils. In nanoparticle form, curcumin is water‐soluble and can efficiently interact with amyloid protein/peptide, offering enhanced performance in inhibiting amyloid fibrillation and dissolving amyloid fibrils. Our results imply that nanoparticle‐based artificial molecular chaperones may offer a promising therapeutic approach to combat neurodegenerative disease.
Stickstofffixierung in Lösung durch einen Eisenkomplex
Authors: Jaenicke Lothar 
Published: April 2014

AbstractAls Fritz Haber in den noch‐Friedensjahren kurz vor dem ersten Weltkrieg die katalytische bergauf‐Ammoniak‐Synthese unter hohem Druck und ziemlich hoher Temperatur ersann, war man noch wenig energiebewusst, befand sich noch buchstäblich im Dampfmaschinen‐Zeitalter. In den hundert Jahren seither sind wir ökonomisch einsichtiger geworden, auch tätiger, das Haber‐Bosch‐Verfahren durch naturnähere Synthesen zu ersetzen. Denn Mikoorganismen, besonders die in Symbiose mit Pflanzenwurzeln lebenden Rhizobium‐Knöllchenbakterien, hydrogenieren N2 zu NH3 unter Umweltbedingungen durch spezielle Übergangsmetall(FeMo)‐Coenzyme in einem von uns noch immer nicht recht verstandenen Prozess.
Kohlenhydrate spielen Protein
Authors: Groß Michael 
Published: April 2014

AbstractViele wichtige Proteine, etwa der Blutfarbstoff Hämoglobin, assoziieren sich in reversibler Reaktion zu wohldefinierten Oligomeren. Erst jetzt wurde ein solches Verhalten mittels der analytischen Ultrazentrifugation auch für Kohlenhydrate nachgewiesen.
Was hat Tryptophan mit Krebs und Parkinson zu tun?
Authors: Heiland Ines 
Published: April 2014

AbstractTryptophan ist den meisten Chemikern bekannt als essentielle Aminosäure und damit Basis für die Synthese von Proteinen. Allerdings wird selbst in Geweben mit hoher Zellteilungsaktivität nur ein Bruchteil des mit der Nahrung aufgenommenen Tryptophans in Proteine integriert. Der überwiegende Teil wird verstoffwechselt und dadurch in andere biologisch aktive Substanzen umgewandelt (Abbildung 1). Abnormalitäten im Tryptophanstoffwechsel wurden bei neurodegenerativen Erkrankungen und Hirntumoren beobachtet.
A spline‐based semiparametric sieve likelihood method for over‐dispersed panel count data
Authors: Hua Lei , Zhang Ying , Tu Wanzhu 
Published: April 2014

AbstractIn this article we study a Gamma‐Frailty inhomogeneous Poisson process model for analysing over‐dispersed panel count data. A cubic B‐spline function is used to approximate the logarithm of the baseline mean function in the semiparametric proportional mean model. The regression parameters and spline coefficients are jointly estimated by maximizing a spline‐based sieve pseudo‐likelihood and by replacing the nuisance over‐dispersion parameter with its moment estimate. The asymptotic properties of the proposed maximum pseudo likelihood estimator, including its consistency, convergence rate and the asymptotic normality of the estimated regression parameters, are thoroughly studied using modern empirical process theory. A spline‐based least‐squares standard error estimator is developed to facilitate robust inference for the regression parameters. Simulation studies are conducted to investigate finite sample performance of the proposed method and robustness of the Gamma‐Frailty inhomogeneous Poisson process model. Finally, for illustration, the method is used to analyse data from an observational study of sexually transmitted infection (STI) in young women. The Canadian Journal of Statistics 42: 217–245; 2014 © 2014 Statistical Society of Canada
Choline phosphate cytidylyltransferase‐α is a novel antigen detected by the anti‐ERCC1 antibody 8F1 with biomarker value in patients with lung and head and neck squamous cell carcinomas
Authors: Vaezi Alec E. , Bepler Gerold , Bhagwat Nikhil R. , Malysa Agnes , Rubatt Jennifer M. , Chen Wei , Hood Brian L. , Conrads Thomas P. , Wang Lin , Kemp Carolyn E. , Niedernhofer Laura J. 
Published: April 2014

BACKGROUNDThe determination of in situ protein levels of ERCC1 with the 8F1 monoclonal antibody is prognostic of survival in patients with non‐small cell lung cancer (NSCLC). The authors previously demonstrated that 8F1 recognizes a second nuclear antigen. This antigen was identified and its value as a biomarker of clinical outcomes analyzed.METHODSThe second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry of 187 early‐stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCCs) was used to examine the influence of the second antigen on 8F1 immunoreactivity and its association with patient outcomes.RESULTSCholine phosphate cytidylyltransferase‐α (CCTα, also known as phosphate cytidylyltransferase 1 choline alpha [PCYT1A], a phospholipid synthesis enzyme regulated by RAS) is the second antigen recognized by 8F1. In NSCLC samples, CCTα contributed (rho, 0.38) to 8F1 immunoreactivity. In samples of squamous cell carcinomas of the lung, CCTα was found to be the dominant determinant of 8F1 immunoreactivity, whereas its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was found to be prognostic of longer disease‐free survival (log‐rank P = .002) and overall survival (log‐rank P = .056). Similarly, in patients with HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho, 0.74), and high CCTα expression was found to be prognostic of survival (log‐rank P = .022 for disease‐free survival and P = .027 for overall survival).CONCLUSIONSCCTα is the second antigen detected by 8F1. High CCTα expression appears to be prognostic of survival in patients with NSCLC who are treated by surgery alone and patients with HNSCC. CCTα is a promising biomarker of patient survival and deserves further study. Cancer 2014;120:1898–1907. © 2014 American Cancer Society.
Influence of conformal radiotherapy technique on survival after chemoradiotherapy for patients with stage III non‐small cell lung cancer in the National Cancer Data Base
Authors: Sher David J. , Koshy Matthew , Liptay Michael J. , Fidler Mary Jo 
Published: April 2014

BACKGROUNDDefinitive chemoradiotherapy is a core treatment modality for patients with stage III non‐small cell lung cancer (NSCLC). Although radiotherapy (RT) technologies have advanced dramatically, to the authors' knowledge relatively little is known regarding the importance of irradiation technique on outcome, particularly given the competing risk of distant metastasis. The National Cancer Data Base was used to determine predictors of overall survival (OS) in patients with AJCC stage III NSCLC who were treated with chemoradiotherapy, focusing on the importance of conformal RT (CRT).METHODSPatients with stage III NSCLC who were treated with chemoradiotherapy between 2003 and 2005 in the National Cancer Data Base were included. RT technique was defined as conventional, 3‐dimensional–conformal, or intensity‐modulated RT (IMRT), the latter 2 combined as CRT. Cox proportional hazards regression was performed for univariable and multivariable analyses of OS.RESULTSThe median, 3‐year, and 5‐year survival outcomes for the 13,292 patients were 12.9 months, 19%, and 11%, respectively. The 3‐year and 5‐year survival probabilities of patients receiving CRT versus no CRT were 22% versus 19% and 14% versus 11%, respectively (P < .0001). On multivariable analysis, CRT was found to be significantly associated with improved OS (hazards ratio, 0.89). This effect was confirmed on sensitivity analyses, including restricting the cohort to minimum 6‐month survivors, young patients with stage IIIA disease, and propensity score‐matching. Institutional academic status and patient volume were not found to be associated with OS.CONCLUSIONSCRT was found to be independently associated with a survival advantage. These results reflect the importance of optimal locoregional therapy in patients with stage III NSCLC and provide motivation for further study of advanced RT technologies in patients with NSCLC. Cancer 2014;120:2060–2068. © 2014 American Cancer Society.
Mechanistic Investigation into the Cleavage of a Phosphomonoester Mediated by a Symmetrical Oxyimine‐Based Macrocyclic Zinc(II) Complex
Authors: Zhang Xuepeng , Xu Xianyan , Xu Huiying , Zhang Xiting , Phillips David Lee , Zhao Cunyuan 
Published: April 2014

AbstractDensity functional calculations are utilized to explore the hydrolysis mechanisms of the phosphomonoester 4‐nitrophenyl phosphate catalyzed by a symmetrical zinc(II) complex. The formation process and properties of the active catalyst are verified. Eight plausible mechanisms are proposed and categorized into three groups. All of the proposed mechanisms, except for Mechanism 7 (see text), are SN2‐type addition–substitution reaction pathways. Nucleophilic attack at the ortho position occurs in Mechanism 7 with a relatively high reaction barrier. Mechanisms 1 and 2 in the monocatalyst model, Mechanisms 5 to 7 in the sandwich‐dual‐catalyst model, as well as the nucleophilic addition–substitution step in Mechanism 8 are concerted reaction pathways, whereas the rest appear to occur in a stepwise manner. Meanwhile, the explicit solvent model is utilized to consider direct hydrogen bonds and solvation interactions and these results indicate that the added water molecule is involved in the hydrolysis process, but does not change the mechanisms significantly. Mechanism 8, with the lowest reaction barrier, is the most favored reaction pathway of the eight proposed mechanisms, although Mechanisms 1, 4, and 6 are in competition with Mechanism 8. In consideration of the zinc(II) complex concentration, Mechanism 1 is only the predominant reaction pathway at a low zinc(II) complex concentration; Mechanisms 4 and 6 tend to be more competitive with increasing concentration of the zinc(II) complexes, and Mechanism 8 is favored at high zinc(II) complex concentrations. Our calculated results are consistent with, and can be used to systematically interpret, experimental observations. More importantly, insightful suggestions are made regarding the catalyst design and selection of the reaction environment.