bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gab1 mediates hepatocyte growth factor‐stimulated mitogenicity and morphogenesis in multipotent myeloid cells
Authors: Felici Angelina , Giubellino Alessio , Bottaro Donald P. 
Published: May 2010

AbstractHepatocyte growth factor (HGF)‐stimulated mitogenesis, motogenesis and morphogenesis in various cell types begins with activation of the Met receptor tyrosine kinase and the recruitment of intracellular adaptors and kinase substrates. The adapter protein Gab1 is a critical effector and substrate of activated Met, mediating morphogenesis, among other activities, in epithelial cells. To define its role downstream of Met in hematopoietic cells, Gab1 was expressed in the HGF‐responsive, Gab1‐negative murine myeloid cell line 32D. Interestingly, the adhesion and motility of Gab1‐expressing cells were significantly greater than parental cells, independent of growth factor treatment. Downstream of activated Met, Gab1 expression was specifically associated with rapid Shp‐2 recruitment and activation, increased mitogenic potency, suppression of GATA‐1 expression and concomitant upregulation of GATA‐2 transcription. In addition to enhanced proliferation, continuous culture of Gab1‐expressing 32D cells in HGF resulted in cell attachment, filopodia extension and phenotypic changes suggestive of monocytic differentiation. Our results suggest that in myeloid cells, Gab1 is likely to enhance HGF mitogenicity by coupling Met to Shp‐2 and GATA‐2 expression, thereby potentially contributing to normal myeloid differentiation as well as oncogenic transformation. J. Cell. Biochem. 111: 310–321, 2010. © 2010 Wiley‐Liss, Inc.
Opposite expression of securin and γ‐H2AX regulates baicalein‐induced cancer cell death
Authors: Jiang Ren‐Huei , Su Wen‐Chi , Liu Huei‐Fang , Huang Hou‐Syun , Chao Jui‐I 
Published: May 2010

AbstractSecurin and γ‐H2AX have been shown to regulate cell survival and genomic stability. However, it is still unknown how the expression and regulation of these proteins is altered following treatment with baicalein, a natural flavonoid extracted from the Scutellaria baicalensis root. In the present study, we investigate the possible roles of securin and γ‐H2AX in baicalein‐induced cancer cell death. Baicalein reduced cell viability in a variety of human cancer cell lines, including bladder, cervical, colon, and lung cancer cells. Interestingly, baicalein treatment (40–80 µM for 24 h) markedly inhibited securin expression, while the levels of γ‐H2AX were elevated. Abnormal spindle formation and chromosomal segregation were induced by baicalein. Furthermore, wild type HCT116 cancer cells had a higher incidence of cytotoxicity and apoptosis than securin‐null HCT116 cells following treatment with baicalein. In contrast, baicalein increased the levels of γ‐H2AX to a similar extent in both cell types. Transfection with H2AX siRNA further increased baicalein‐induced cell death. Additionally, blockade of the AKT pathway by treatment with wortmannin or AKT shRNA lowered the levels of γ‐H2AX and enhanced cytotoxicity in baicalein‐treated cells. Taken together, our findings suggest that the opposing effects of baicalein on securin and γ‐H2AX levels may be involved in the regulation of cell viability and genomic stability by this compound. J. Cell. Biochem. 111: 274–283, 2010. © 2010 Wiley‐Liss, Inc.
About the synthesis of N‐1‐substituted 3‐aminopyrroles. A comparison
Authors: Almerico Anna Maria , Cirrincione Girolamo , Aiello Enrico , Dattolo Gaetano 
Published: May 2010

AbstractA general method for the preparation of 3‐amino‐1‐methylpyrroles in excellent yields is reported. The key step involves the N‐methylation of the nitro derivatives 2, under phase transfer catalysis conditions.
Studies on pyrrolidinones. Synthesis of 5‐(5‐oxo‐2‐pyrrolidinyl)‐1,2,4‐triazole‐3‐thione derivatives
Authors: Rigo Benoít , Couturier Daniel 
Published: May 2010

AbstractStarting from readily available pyroglutamic esters 1, some new 1,2,4‐triazole‐3‐thione derivatives, bonded to a pyrrolidinone ring were synthesized and are characterized by their spectral data.
10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds—whole‐body autoradiography (WBA)‐drug discovery and development Session 3: Monday, June 15, 2009
Authors: Whitby Brian , Lordi Alfred 
Published: May 2010

AbstractThe use of QWBA and MARG in studying tissue distribution of receptor binding proteins was discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Radiosynthesis of the HIV integrase inhibitor [18F]MK‐0518 (Isentress)
Authors: Li Wenping , Thompson Wayne , Fisher Thorsten , Wai John S. , Hazuda Daria , Burns H. Donald , Hamill Terence G. 
Published: May 2010

AbstractThe human immunodeficiency virus integrase inhibitor, [18F]MK‐0518, was prepared via a three‐step, one‐pot radiosynthesis. [18F]4‐Fluorobenzylamine was produced from the fluorination of 4‐cyano‐N,N,N‐trimethylammonium triflate with [18F]fluoride and reduction with borane methylsulfide complex in 50–68% radiochemical yield. The final step, the coupling of [18F]4‐fluorobenzylamine with an ester coupling partner, achieved an overall uncorrected radiochemical yield after HPLC purification of ∼2%, based on the starting [18F]fluoride. In a typical run, the total synthesis time was about 90 min and gave 0.37–1.74 GBq (10–47 mCi) of [18F]MK‐0518. The radiochemical purity of [18F]MK‐0518 was>98% and the specific activity was 243–1275 Ci/mmol (EOS, n=4). A convenient three‐step, one‐pot radiosynthesis of [18F]MK‐0518 via [18F]4‐fluorobenzylamine has been developed, giving sufficient quantities of [18F]MK‐0518 for animal positron emission tomography studies. Copyright © 2010 John Wiley & Sons, Ltd.
MALDI linear TOF mass spectrometry of PEGylated (glyco)proteins
Authors: Seyfried Birgit K. , Siekmann Jürgen , Belgacem Omar , Wenzel Ryan J. , Turecek Peter L. , Allmaier Günter 
Published: May 2010

AbstractPEGylation of proteins is a fast growing field in biotechnology and pharmaceutical sciences owing to its ability to prolong the serum half‐life time of recombinant proteins. Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI TOF MS) has been shown to be a powerful tool in the analysis of several PEGylated small proteins. Here we present data obtained with a standard secondary electron multiplier (SEM) and a high mass (HM) detector combined with a MALDI linear TOF MS system for the detection of PEGylated (glyco)proteins in the range of 60–600 kDa. Examples of MALDI TOF MS of small (interferon α2a), middle (human serum albumin (HSA)) and high molecular mass proteins (coagulation factor VIII and von Willebrand factor (vWF), both heavily glycosylated proteins) are presented. The particular challenge for the analysis was the heterogeneity of the (glyco)proteins in the high molecular weight range in combination with additional PEGylation, which even introduced more heterogeneity and was more challenging for interpretation. Nevertheless, the performance of MALDI linear TOF MS with both detector systems in terms molecular weight and heterogeneity determination depending on the m/z range was superior to the other methods. Although the SEM was able to obtain information about protein PEGylation in the mass range up to 100 kDa (e.g. PEGylated HSA), the HM system was crucial for detection of HM ions (e.g. PEGylated recombinant vWF), which was impossible with the standard SEM. Copyright © 2010 John Wiley & Sons, Ltd.
L‐Valine assisted distinction between the stereo‐isomers of D‐hexoses by positive ion ESI tandem mass spectrometry
Authors: Li Gang , Huang Zhongbin , Fu Chuan , Xu Pengxiang , Liu Yan , Zhao Yu‐fen 
Published: May 2010

AbstractThe binary mixtures of 7 hexoses and 20 amino acids were investigated by electrospray ionization ion trap mass spectrometry (ESI‐ITMS). The adduct ions of the amino acid and the hexose were detected for 12 amino acids but not for the other 8 amino acids which are basic acidic amino acids and amides. The ions of amino acid–hexose complexes were further investigated by tandem mass spectrometry (MS/MS), and some of them just split easily into two parts whereas the others gave rich fragmentation, such as the complex ions of isoleucine, phenylalanie, tyrosine, and valine. We found that hexoses could be complexed by two molecules of valine but only by one molecule of the other amino acids. Among seven kinds of valine–hexose complexes coordinated by potassium ion, the MS2 spectra of the ion at m/z 453 yielded unambiguous differentiation. And the fragmentation ions are sensitive to the stereochemical differences at the carbon‐4 of hexoses in the complexes, as proved by the MS2. Copyright © 2010 John Wiley & Sons, Ltd.
Differentiation of Boc‐protected α,δ‐/δ,α‐ and β,δ‐/δ,β‐hybrid peptide positional isomers by electrospray ionization tandem mass spectrometry
Authors: Raju G. , Ramesh V. , Srinivas R. , Sharma G. V. M. , Shoban Babu B. 
Published: May 2010

AbstractTwo new series of Boc‐N‐α,δ‐/δ,α‐ and β,δ‐/δ,β‐hybrid peptides containing repeats of L‐Ala‐δ5‐Caa/δ5‐Caa‐L‐Ala and β3‐Caa‐δ5‐Caa/δ5‐Caa‐β3‐Caa (L‐Ala = L‐alanine, Caa = C‐linked carbo amino acid derived from D‐xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion trap tandem mass spectrometry (MS/MS). MSn spectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Boc‐group, and the side chain. The dipeptide positional isomers are differentiated by the collision‐induced dissociation (CID) of the protonated peptides. The loss of 2‐methylprop‐1‐ene is more pronounced for Boc‐NH‐L‐Ala‐δ‐Caa‐OCH3 (1), whereas it is totally absent for its positional isomer Boc‐NH‐δ‐Caa‐L‐Ala‐OCH3 (7), instead it shows significant loss of t‐butanol. On the other hand, second isomeric pair shows significant loss of t‐butanol and loss of acetone for Boc‐NH‐δ‐Caa‐β‐Caa‐OCH3 (18), whereas these are insignificant for its positional isomer Boc‐NH‐β‐Caa‐δ‐Caa‐OCH3 (13). The tetra‐ and hexapeptide positional isomers also show significant differences in MS2 and MS3 CID spectra. It is observed that ‘b’ ions are abundant when oxazolone structures are formed through five‐membered cyclic transition state and cyclization process for larger ‘b’ ions led to its insignificant abundance. However, b1+ ion is formed in case of δ,α‐dipeptide that may have a six‐membered substituted piperidone ion structure. Furthermore, ESI negative ion MS/MS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MS/MS of pairs of di‐, tetra‐, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers. Copyright © 2010 John Wiley & Sons, Ltd.
Spectroscopy study of mural paintings from the Pyrenean Church of Saint Eulàlia of Unha
Authors: Clark Robin J. H. , Hark Richard R. , Salvadó Nati , Butí Salvador , Pradell Trinitat 
Published: May 2010

AbstractA series of wall paintings dating from the Romanesque period to the 16th century were uncovered during restoration projects at the church of Santa Eulàlia of Unha in the Val d'Aran. This study centres on the use of complementary spectroscopic techniques to examine comprehensively the pigments, binders and other materials associated with these mural paintings. These include Raman microscopy, far and mid‐Fourier transform infrared (FTIR) spectroscopy both with synchrotron radiation (SR), as well as optical microscopy and scanning electron microscopy (SEM‐EDS), and build upon earlier SR‐X‐ray diffraction studies. Traditional materials such as hematite, goethite, vermilion, red lead, carbon black and calcite were identified, but the artists' palette varied with the period. The blue pigment identified in the Romanesque frescoes was determined to be aerinite, a rare Fe(II)/Fe(III)‐containing aluminosilicate found locally in the Pyrenees region. Electronic, Raman and far‐SR‐FTIR spectra of this pigment are presented for the first time in the context of a work of art. The presence of some nitrates, sulphates and oxalates found in the mural paintings is commented upon. Copyright © 2010 John Wiley & Sons, Ltd.
Model for estimating the threshold mechanical stability of structural cartilage grafts used in rhinoplasty
Authors: Zemek Allison , Garg Rohit , Wong Brian J. F. 
Published: May 2010

AbstractObjectives/Hypothesis:Characterizing the mechanical properties of structural cartilage grafts used in rhinoplasty is valuable because softer engineered tissues are more time‐ and cost‐efficient to manufacture. The aim of this study is to quantitatively identify the threshold mechanical stability (e.g., Young's modulus) of columellar, L‐strut, and alar cartilage replacement grafts.Study Design:Descriptive, focus group survey.Methods:Ten mechanical phantoms of identical size (5 × 20 × 2.3 mm) and varying stiffness (0.360 to 0.85 MPa in 0.05 MPa increments) were made from urethane. A focus group of experienced rhinoplasty surgeons (n = 25, 5 to 30 years in practice) were asked to arrange the phantoms in order of increasing stiffness. Then, they were asked to identify the minimum acceptable stiffness that would still result in favorable surgical outcomes for three clinical applications: columellar, L‐strut, and lateral crural replacement grafts. Available surgeons were tested again after 1 week to evaluate intra‐rater consistency.Results:For each surgeon, the threshold stiffness for each clinical application differed from the threshold values derived by logistic regression by no more than 0.05 MPa (accuracy to within 10%). Specific thresholds were 0.56, 0.59, and 0.49 MPa for columellar, L‐strut, and alar grafts, respectively. For comparison, human nasal septal cartilage is approximately 0.8 MPa.Conclusions:There was little inter‐ and intra‐rater variation of the identified threshold values for adequate graft stiffness. The identified threshold values will be useful for the design of tissue‐engineered or semisynthetic cartilage grafts for use in structural nasal surgery.
Under the microscope: Assessing surgical aptitude of otolaryngology residency applicants
Authors: Carlson Matthew L. , Archibald David J. , Sorom Abraham J. , Moore Eric J. 
Published: May 2010

AbstractObjectives/Hypothesis:Application to otolaryngology residency is a highly competitive process. Programs identify the best candidates by evaluating academic performance in medical school, board scores, research experience, performance during an interview, and letters of recommendation. Unfortunately, none of these metrics completely assess an applicant's capacity to learn and perform surgical skills. We describe a direct assessment of an applicant's ability for rapid surgical skill acquisition, manual dexterity, and response to stress that can be performed during the interview process.Study Design:A retrospective study at an academic otolaryngology residency program.Methods:After orientation, applicants were seated at a microsurgical training station and allotted 20 minutes to suture an incision using 10‐0 nylon suture on a latex practice card. Their performance was graded using a 1‐to‐5 scoring system for the following categories: microscope use, respect for tissue, instrument handling, knot tying and suture control, skills acquisition, and attitude toward the exercise. Applicants were given some instruction and assessed on their ability to incorporate what they had learned into their technique.Results:The average total applicant score was 23.2, standard deviation (SD) 3.6 (maximum 30); 13.4% of applicants scored <1 SD below the mean, 66.1% scored within 1 SD of the mean, and 20.5% scored >1 SD above the mean.Conclusions:The value of applicant screening tests in predicting surgical competency is controversial. We describe a direct assessment tool that may prove useful in identifying outliers, both high and low, to aid in final applicant ranking.
Teasing out the best molecular marker in the AKT/mTOR pathway in head and neck squamous cell cancer patients
Authors: Clark Cheryl , Shah Shivang , Herman‐Ferdinandez Lilantha , Ekshyyan Oleksandr , Abreo Fleurette , Rong Xiaohua , McLarty Jerry , Lurie Aubrey , Milligan Edward J. , Nathan Cherie‐Ann O. 
Published: May 2010

AbstractObjectives/Hypothesis:No reliable molecular biomarker is currently available for clinical application in the management of head and neck cancer patients. The AKT/mTOR pathway is activated in 90% to 100% of head and neck squamous cell cancer (HNSCC) and could be promising biomarkers closely linked to cancer incidence.Study Design:Retrospective study of HNSCC and non‐cancer patients.Methods:Oral mucosa from noncancer patients were compared to HNSCC tumors and junctional zone mucosa. The candidate biomarkers mTOR, AKT, 4EBP1, and S6 kinase, signaling components upstream and downstream of mTOR that appear dysregulated in HNSCC, were evaluated using immunohistochemistry (IHC) and Western blot analysis.Results:Expression of phosphorylated AKT and phosphorylated mTOR were significantly higher in cancer patient tumors compared to noncancer oral mucosa samples (P = .004 and P = .026, respectively) by Western blot analysis. Expression of p‐mTOR and p‐4EBP1 were higher in patient junctional zones compared to tumors (p = 0.017 and p = 0.022, respectively) and no difference in p‐AKT or p‐S6 expression in HNSCC patients' junctional zone compared to tumors. IHC‐demonstrated p‐mTOR expression was 81.9% sensitive and 100% specific in differentiating cancer from noncancer mucosa, whereas p‐4EBP1 expression by IHC was only 50.0% sensitive and 95.5% specific in differentiating normal mucosa from HNSCC (P < .01).Conclusions:Phosphorylated mTOR appears to be a reliable biomarker by both Western blot analysis (P = .026) and IHC in human head and neck cancer (P < .001). Moreover, phosphorylated AKT, which is immediately upstream of mTOR, is a potential biomarker that should be further studied. Clinical trials with mTOR inhibitors are being evaluated for HNSCC, and selecting patients that are likely to respond to these inhibitors requires identifying and validating predictive biomarkers of response.
Perioperative medication errors in otolaryngology
Authors: Rosenwasser Rebecca , Winterstein Almut G. , Rosenberg Amy F. , Rosenberg Eric I. , Antonelli Patrick J. 
Published: May 2010

AbstractObjectives/Hypothesis:Medication errors are a common cause of poor clinical outcomes. Information on perioperative medication errors is scarce. This study was aimed at identifying the nature, cause, and potential remedies for medication errors in otolaryngologic surgery.Study Design:Prospective and descriptive.Methods:Clinicians were incentivized for reporting possible medication errors that occurred from the preoperative through the first postoperative clinic visit over a 2‐month period. Each report was investigated by an expert panel to determine validity, preventability, contributing factors, and potential preventative measures. A random sample of procedures and clinic visits were monitored for compliance with safe medication practices and information flow.Results:From 589 surgeries, 20 medication errors were reported (two preoperative, four operative, five during hospital admission, two in transition between services, four during discharge, and three postoperative). Errors included wrong dose (seven), omitted dose (six), wrong drug (five), wrong site (two), and unnecessary drug (one). Causes included failure to consider weight‐based dosing, use accurate drug references, calculate the total medication supply needed, verify the administration site, consider pertinent patient information (e.g., allergies), reconcile medications upon transfers, and document medication histories. Use of preprinted order forms was flawed, and discharge instructions were insufficient to guide patients postoperatively.Conclusions:Failure to adhere to safe medication‐use practices occurred throughout perioperative care. Improvement in medication documentation, following established safe practices, integration of patient information in prescribing decisions, and use of clinical decision support systems appear necessary to prevent perioperative medication errors in otolaryngology.
Prospective clinical phase II study of two new indwelling voice prostheses (Provox Vega 22.5 and 20 Fr) and a novel anterograde insertion device (Provox Smart Inserter)
Authors: Hilgers Frans J. M. , Ackerstaff Annemieke H. , Jacobi Irene , Balm Alfons J. M. , Tan I. Bing , van den Brekel Michiel W. M. 
Published: May 2010

AbstractObjectives/Hypothesis:To assess device life of the new Provox Vega 22.5 and 20 Fr prostheses, to establish whether the optimized airflow characteristics of these devices materialize in better voice characteristics in comparison to Provox2, and to assess the feasibility of voice prosthesis replacement with the new Smart Inserter.Study Design:Prospective clinical phase II study.Methods:Prospective clinical phase II study including two patient cohorts (Provox Vega 22.5 Fr: N = 33; Provox Vega 20 Fr: N = 26). Device‐life assessment, subjective data collection with study‐specific structured questionnaires, perceptual analysis (Comparative Mean Opinion Score), and objective voice analysis (standard Dutch text, maximum phonation time, and dynamic range).Results:Device life of both prostheses appears comparable to Provox2. Several voice characteristics were better in Vega 22.5, which coincides well with patients' preference. Voicing with Vega 20 appears comparable to Provox2. Use of Smart Inserter showed a short learning curve, and was considered an improvement by the clinicians.Conclusions:The new Provox Vega 22.5 and 20 Fr prostheses have a device life comparable to Provox2, whereas voicing is better than (with the 22.5Fr version) or comparable (with the 20 Fr version) to Provox2. The Smart Inserter, after a short learning curve, turns out to be a further improvement of the anterograde replacement of these indwelling devices.
Multiple nontrivial solutions for resonant Neumann problems
Authors: Filippakis Michael , Papageorgiou Nikolaos S. 
Published: May 2010

AbstractWe consider semilinear second order elliptic Neumann problems, which are resonant both at infinity (with respect to an eigenvalue λk, k ≥ 1) and at zero (with respect to the principal eigenvalue λ0 = 0). Using techniques from Morse theory, combined with variational methods, we are able to show that the problem has at least four nontrivial smooth solutions (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)