bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection
Authors: Nambiar Jonathan K. , Ryan Anthony A. , U. Kong Carlyn , Britton Warwick J. , Triccas James A. 
Published: October 2009

AbstractThe rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1−/− mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.
IL‐24 protects against Salmonella typhimurium infection by stimulating early neutrophil Th1 cytokine production, which in turn activates CD8+ T cells
Authors: Ma Yunfeng , Chen Haidan , Wang Qilong , Luo Fengling , Yan Jun , Zhang Xiao‐Lian 
Published: October 2009

AbstractSalmonella are important intracellular pathogens in humans and other animal hosts. IL‐24 is a novel tumour suppressor and can mediate induction of Th1‐type cytokines from PBMC. However, the immunological consequences of this cytokine during intracellular pathogen infection in vivo remain unclear. In the present study, we used a virulent S. typhimurium C5 infected mouse model of typhoid fever to demonstrate that administration of exogenous IL‐24 had a protective effect against the bacteria. The IL‐24 glycosylation site mutant, in contrast, showed a decreased protective effect. Furthermore, the protective effect of IL‐24 was abrogated in IFN‐γ KO mice. More importantly, we demonstrated that IL‐24 predominately stimulated neutrophils to produce IFN‐γ and IL‐12, subsequently activating CD8+ T cells both in vivo and in vitro. In addition, IL‐24 could induce neutrophils to produce NO. These data indicate that the neutrophils activated by IL‐24 may play important roles in host defence against Salmonella infection in vivo. Our findings support the development of a novel cytokine immunotherapy against Salmonella.
Soluble HLA‐I‐mediated secretion of TGF‐β1 by human NK cells and consequent down‐regulation of anti‐tumor cytolytic activity
Authors: Ghio Massimo , Contini Paola , Negrini Simone , Boero Silvia , Musso Alessandra , Poggi Alessandro 
Published: October 2009

AbstractSoluble HLA class I (sHLA‐I) molecules can regulate survival of NK cells and their anti‐tumor killing activity. Herein, we have analysed whether interaction of sHLA‐I with CD8 and/or different isoforms of killer Ig‐like receptors (KIR) induced secretion of transforming growth factor (TGF)‐β1. CD8+KIR− NK cell clones secreted TGF‐β1 upon the interaction of sHLA‐I with CD8 molecule. sHLA‐Cw4 or sHLA‐Cw3 alleles engaging inhibitory isoforms of KIR, namely KIR2DL1 or KIR2DL2, strongly downregulated TGF‐β1 production elicited through CD8. On the other hand, sHLA‐Cw4 or sHLA‐Cw3 alleles induced secretion of TGF‐β1 by ligation of stimulatory KIR2DS1 or KIR2DS2 isoforms. TGF‐β1 strongly reduced NK cell‐mediated tumor cell lysis and production of pro‐inflammatory cytokines such as TNF‐α and IFN‐γ. Also, TGF‐β1 inhibited NK cell cytolysis induced by the engagement of stimulatory receptors including NKG2D, DNAM1, 2B4, CD69, NKp30, NKp44 and NKp46. The IL‐2‐dependent surface upregulation of some of these receptors was prevented by TGF‐β1. Furthermore, TGF‐β1 hampered IL‐2‐induced NK cell proliferation but not IL‐2‐mediated rescue from apoptosis of NK cells. Depletion of TGF‐β1 restored all the NK cell‐mediated functional activities analysed. Taken together these findings suggest that sHLA‐I antigens may downregulate the NK cell‐mediated innate response by inducing TGF‐β1 release.
NKT cells: Friend or foe during viral infections?
Authors: Diana Julien , Lehuen Agnès 
Published: October 2009

AbstractNKT cells are innate‐like T lymphocytes that are found in rodents and primates. They are non‐conventional T cells restricted by the CD1d molecule that presents self and exogenous glycolipids. NKT cells are unique in their ability to promptly secrete copious amounts of cytokines such as IFN‐γ and IL‐4. Once activated, NKT cells can provide maturation signals to downstream cells, including DC, NK cells, and lymphocytes, thereby contributing to both innate and acquired immunity. Accordingly, NKT cells can influence a wide array of immune responses, including tumor surveillance, maintenance of self‐tolerance and anti‐infectious defenses. Studies performed with NKT‐cell‐deficient mice have shown that these cells are critical for the clearance of various pathogens. During bacterial infections, NKT cells can be activated either indirectly by DC or directly by bacterial lipid antigens presented by CD1d. Although viruses do not contain lipid antigens, NKT cells have also been implicated in antiviral responses. The capacity of NKT cells to regulate viral immune‐surveillance, either constitutively or post‐activation, makes them an attractive clinical target. In this review, we summarize recent publications dealing with the functions and relevance of NKT cells in the context of viral infections, both in murine models and in humans.
Metal‐Hydride Bonding in Higher Alkali Metal Boron Monohydrides
Authors: Haywood Joanna , Wheatley Andrew E. H. 
Published: October 2009

AbstractThe recent demonstration that hydride translocation involving alkali metal boron monohydrides can be utilised to trap hydride in metal clusters has led to investigation of the alkali metal salts of triethylborohydride, [Et3BH]–. Treatment of Et3BHM (M = Li, Na, K) with the polydentate donors (L) N,N,N′,N′‐tetramethylethylenediamine (TMEDA) and N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA) is reported. For M = Li, L = TMEDA ion separation is noted, with the metal ion encapsulated by two donor ligands. In contrast, for M = Na, K the TMEDA‐solvates reveal hydride‐bridged centro‐symmetric dimers based on M2H2‐metallocyclic cores. X‐ray diffraction reveals mean Na–H and K–H distances of 2.29 and 2.55 Å, respectively. For M = K, the PMDETA‐solvate is also reported, with the hydride‐bridged dimer motif being retained, with an expanded mean metal–hydride distance of 2.67 Å. Solution data and 1JBH coupling constants are reported in both polar and non‐polar solvents.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Specific Ca2+ Fluorescent Sensor: Signaling by Conformationally Induced PET Suppression in a Bichromophoric Acridinedione
Authors: Ashokkumar Pichandi , Ramakrishnan Vayalakkavoor T. , Ramamurthy Perumal 
Published: October 2009

AbstractA series of acridinedione‐based bichromophoric podand systems 1a–c were synthesized and characterized. Among these, bichromophore 1c shows specific binding of Ca2+ in the presence of other biologically important metal ions like Na+, K+, Mg2+, and Zn2+. The selective complexation was proved by steady‐state emission, time‐resolved emission, and 1H NMR titration. Signaling of the binding event was achieved by Ca2+‐induced folding of the bichromophore, resulting in PET suppression in the acridinedione chromophore. Involvement of a PET process in the optical signaling was confirmed by comparing bichromophores 1a–c with non‐PET compound 2 and monochromophore model compound 3. Non‐PET compound 2 failed to give optical response upon Ca2+ binding as a result of the absence of a PET process in the Ca2+‐bound complex. Monochromophore 3 shows a similar optical response, which is the same as that in 1c. Titration of the metal‐ion‐bound complex of 1c with EDTA released the metal ion from the complex, thereby regaining the original photophysical properties of the bichromophore.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Dehydro‐β‐amino Acid Containing Peptides as Promising Sequences for Drug Development
Authors: Cardillo Giuliana , Gennari Arianna , Gentilucci Luca , Mosconi Elisa , Tolomelli Alessandra , Troisi Stefano 
Published: October 2009

AbstractIn the course of a program devoted to the synthesis of small peptidic molecules mimicking the RGD (Arg‐Gly‐Asp) motif, the allylic amination of enantiomerically pure carbonates with 4‐substituted benzylamines afforded dehydro‐β‐amino esters through an SN2′ mechanism. The reaction performed with 4‐aminobenzylamine occurred with complete chemoselectivity, as the aliphatic amine was much more reactive than the aromatic one. This allowed useful precursors of biologically active compounds to be obtained, avoiding extra protection–deprotection steps. The same reaction performed on glycine‐derived amides gave similar results, allowing a novel type of RGD mimetic to be prepared, whose ability to inhibit cell adhesion was found to be very promising.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Electroanalysis of Bisphenol A at a Multiwalled Carbon Nanotubes‐gold Nanoparticles Modified Glassy Carbon Electrode
Authors: Tu Xinman , Yan Liushui , Luo Xubiao , Luo Shenglian , Xie Qingji 
Published: October 2009

AbstractA sensitive electrochemical method was developed for the determination of bisphenol A (BPA) at a glassy carbon electrode (GCE) modified with a multiwalled carbon nanotubes (MWCNTs)‐gold nanoparticles (GNPs) hybrid film, which was prepared based on the electrostatic interaction between positively charged cetyltrimethylammonium bromide (CTAB) and negatively charged MWCNTs and GNPs. The MWCNT‐GNPs/GCE exhibited an enhanced electroactivity for BPA oxidation versus unmodified GCE and MWCNTs/GCE. The experimental parameters, including the amounts of modified MWCNTs and GNPs, the pH of the supporting electrolyte, scan rate and accumulation time, were examined and optimized. Under the optimal conditions, the differential pulse voltammetric anodic peak current of BPA was linear with the BPA concentration from 2.0×10−8 to 2×10−5 mol L−1, with a limit of detection of 7.5 nmol L−1. The proposed procedure was applied to determine BPA leached from real plastic samples with satisfactory results.
Novel device for quick measurement of glucose in POCT areas without pre‐analytical steps based on a multi‐way glucose biosensor
Authors: Zahn Dorothea , Szeponik Jan , Gandhi Adrian 
Published: October 2009

AbstractProfessional Point of Care testing demands rapid analysis and professional quality. To assure rapid analysis of high quality the analytical tool ideally should be able to work without sample pre‐treatment and should offer the opportunity to calibrate and/or control the analytical performance of the tool. In contrast to an enormous number of different disposable‐strips used for patient self monitoring today and based on an extended knowledge with respect to multi‐way biosensors used in laboratory analyzers we decided to develop a professional Point of Care Testing system for glucose analysis based on a multi‐way biosensor. The multi‐way glucose biosensor placed in the instrument for 30 days did reduce the lag time between blood withdrawal and availability of a result of lab quality in a bedside area to about 10 seconds. No pre‐analytical steps are necessary for measuring capillary whole blood, no crossing over was observed, and the data could be transferred into a laboratory information system or a hospital information system. Thus, we were able to realize tools for professional health control able to measure glucose values in laboratory quality at places outside laboratories: e.g., in doctor's offices, hospital wards, critical care units, and training units of athletes. By combining the advantages of laboratory analyzers (high quality and low sample price) and the advantages of disposable strips (simple procedure and immediate results after sample withdrawal) with the Glukometer 3000 and LactatProfi 3000 we did start to fill the gap between the two basic technologies available on the market for diagnosis today. Glukometer 3000 and LactatProfi 3000 are worldwide the first and only mobile glucose and lactate measuring instruments for decentralized locations based on multi‐way biosensors.
Testing of dynamically substructured, base‐isolated systems using adaptive control techniques
Authors: Tu J. Y. , Lin P. Y. , Stoten D. P. , Li G. 
Published: October 2009

AbstractExperimental techniques for testing dynamically substructured systems are currently receiving attention in a wide range of structural, aerospace and automotive engineering environments. Dynamic substructuring enables full‐size, critical components to be physically tested within a laboratory (as physical substructures), while the remaining parts are simulated in real‐time (as numerical substructures). High quality control is required to achieve synchronization of variables at the substructuring interfaces and to compensate for additional actuator system(s) dynamics, nonlinearities, uncertainties and time‐varying parameters within the physical substructures. This paper presents the substructuring
approach and associated controller designs for performance testing of an aseismic, base‐isolation system, which is comprised of roller‐pendulum isolators and controllable, nonlinear magnetorheological dampers. Roller‐pendulum isolators are typically mounted between the protected structure and its foundation and have a fundamental period of oscillation far‐removed from the predominant periods of any earthquake. Such semi‐active damper systems can ensure safety and performance requirements, whereas the implementation of purely active systems can be problematic in this respect. A linear inverse dynamics compensation and an adaptive controller are tailored for the resulting nonlinear synchronization problem. Implementation results favourably compare the effectiveness of the adaptive substructuring method against a conventional shaking‐table technique. A 1.32% error resulted compared with the shaking‐table response. Ultimately, the accuracy of the substructuring method compared with the response of the shaking‐table is dependent upon the fidelity of the numerical substructure. Copyright © 2009 John Wiley & Sons, Ltd.
Unfavorable prognosis of CRTC1‐MAML2 positive mucoepidermoid tumors with CDKN2A deletions
Authors: Anzick Sarah L. , Chen Wei‐Dong , Park Yoonsoo , Meltzer Paul , Bell Diana , El‐Naggar Adel K. , Kaye Frederic J. 
Published: October 2009

AbstractThe CRTC1‐MAML2 fusion oncogene underlies the etiology of mucoepidermoid salivary gland carcinoma (MEC) where it confers a favorable survival outcome as compared with fusion‐negative MEC. While these analyses suggested that detection of CRTC1‐MAML2 serves as a useful prognostic biomarker, we recently identified outlier cases of fusion‐positive MEC associated with advanced‐staged lethal disease. To identify additional genetic alterations that might cooperate with CRTC1‐MAML2 to promote disease progression, we performed a pilot high‐resolution oligonucleotide array CGH (aCGH) and PCR‐based genotyping study on 23 MEC samples including 14 fusion‐positive samples for which we had clinical outcome information. Unbiased aCGH analysis identified inactivating deletions within CDKN2A as a candidate poor prognostic marker which was confirmed by PCR‐based analysis (CDKN2A deletions in 5/5 unfavorable fusion‐positive cases and 0/9 favorable fusion‐positive cases). We did not detect either activating EGFR mutations, nor copy number gains at the EGFR or ERBB2 loci as poor prognostic features for fusion‐positive MEC in any of the tumor specimens. Prospective studies with larger case series will be needed to confirm that combined CRTC1‐MAML2 and CDKN2A genotyping will optimally stage this disease. © 2009 Wiley‐Liss, Inc.
FAU regulates carboplatin resistance in ovarian cancer
Authors: Moss Esther L. , Mourtada‐Maarabouni Mirna , Pickard Mark R. , Redman Charles W. , Williams Gwyn T. 
Published: October 2009

AbstractThe development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel‐Biskis‐Reilly murine sarcoma virus (FBR‐MuSV)‐associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short‐interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin‐induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal‐Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin‐induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P < 0.0001). The expression of FAU was examined by quantitative real‐time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal‐Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum‐resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer. © 2009 Wiley‐Liss, Inc.
Mapping quantitative traits in unselected families: algorithms and examples
Authors: Dupuis Josée , Shi Jianxin , Manning Alisa K. , Benjamin Emelia J. , Meigs James B. , Cupples L. Adrienne , Siegmund David 
Published: October 2009

AbstractLinkage analysis has been widely used to identify from family data genetic variants influencing quantitative traits. Common approaches have both strengths and limitations. Likelihood ratio tests typically computed in variance component analysis can accommodate large families but are highly sensitive to departure from normality assumptions. Regression‐based approaches are more robust but their use has primarily been restricted to nuclear families. In this paper, we develop methods for mapping quantitative traits in moderately large pedigrees. Our methods are based on the score statistic, which in contrast to the likelihood ratio statistic can use nonparametric estimators of variability to achieve robustness of the false‐positive rate against departures from the hypothesized phenotypic model. Because the score statistic is easier to calculate than the likelihood ratio statistic, our basic mapping methods utilize relatively simple computer code that performs statistical analysis on output from any program that computes estimates of identity by descent. This simplicity also permits development and evaluation of methods to deal with multivariate and ordinal phenotypes, and with gene‐gene and gene‐environment interaction. We demonstrate our methods on simulated data and on fasting insulin, a quantitative trait measured in the Framingham Heart Study. Genet. Epidemiol. 33:617–627, 2009. © 2009 Wiley‐Liss, Inc.
Extracapsular spread in oral squamous cell carcinoma
Authors: Shaw Richard J. , Lowe Derek , Woolgar Julia A. , Brown James S. , Vaughan E. David , Evans Christopher , Lewis‐Jones Huw , Hanlon Rebecca , Hall Gillian L. , Rogers Simon N. 
Published: October 2009

AbstractBackgroundExtracapsular spread (ECS) in the cervical lymph nodes represents the most significant adverse prognostic indicator in oral squamous cell carcinoma (OSCC).MethodsIn a consecutive cohort of OSCC treated by primary surgery, ECS was seen in 25% (101) of 400 patients.ResultsECS doubled the incidence of local recurrence and distant metastases, but tripled regional failure. The recurrences occurred sooner in ECS than in non‐ECS cases (206 vs 334 days, p = .04). Patients with macroscopic ECS had a 5‐year overall survival (OS) of 19% compared with 31% in microscopic ECS. MRI neck staging offered poor sensitivity, especially in microscopic ECS. Age >75 years, smoking, and heavy use of alcohol were independent predictors of ECS, which may implicate a failure of immunosurveillance by the host as much as adverse biology of the tumor.ConclusionsReporting of ECS is essential in accurate prognostication, and we advocate that all patients with OSCC and ECS should be grouped as pN3 on the basis of their prognosis. © 2009 Wiley Periodicals, Inc. Head Neck, 2010