bluuebunny/crossref_metadata_2025_split huggingface dataset:
VTX-2337 Is a Novel TLR8 Agonist That Activates NK Cells and Augments ADCC
Authors: Lu Hailing , Dietsch Gregory N. , Matthews Maura-Ann H. , Yang Yi , Ghanekar Smita , Inokuma Margaret , Suni Maria , Maino Vernon C. , Henderson Katherine E. , Howbert James Jeffry , Disis Mary L. , Hershberg Robert M. 
Published: December 2011

Abstract
Purpose: We aim to characterize VTX-2337, a novel Toll-like receptor (TLR) 8 agonist in clinical development, and investigate its potential to improve monoclonal antibody–based immunotherapy that includes the activation of natural killer (NK) cells.
Experimental Design: HEK-TLR transfectants were used to compare the selectivity and potency of VTX-2337, imiquimod, CpG ODN2006, and CL075. The ability of VTX-2337 to induce cytokine and chemokine production from human peripheral blood mononuclear cells (PBMC) and activation of specific immune cell subsets was examined. The potential for VTX-2337 to activate NK cell activity through direct and indirect mechanisms was also investigated. Finally, we tested the potential for VTX-2337 to augment antibody-dependent cell-mediated cytotoxicity (ADCC), especially in individuals with low-affinity FcγR3A single-nucleotide polymorphism (SNP).
Results: VTX-2337 selectively activates TLR8 with an EC50 of about 100 nmol/L and stimulates production of TNFα and interleukin (IL)-12 from monocytes and myeloid dendritic cells (mDC). VTX-2337 stimulates IFNγ production from NK cells and increases the cytotoxicity of NK cells against K562 and ADCC by rituximab and trastuzumab. Effects of VTX-2337 on NK cells were, in part, from direct activation as increased IFNγ production and cytotoxic activity were seen with purified NK cells. Finally, VTX-2337 augments ADCC by rituximab in PBMCs with different FcγR3A genotypes (V/V, V/F, and F/F at position 158).
Conclusions: VTX-2337 is a novel small-molecule TLR8 agonist that activates monocytes, DCs, and NK cells. Through the activation of NK cells, it has the potential to augment the effectiveness of monoclonal antibody treatments where a polymorphism in FcγR3A limits clinical efficacy. Clin Cancer Res; 18(2); 499–509. ©2011 AACR.
Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer
Authors: Lee Jih-Hsiang , Giovannetti Elisa , Hwang Jin-Hyeok , Petrini Iacopo , Wang Qiuyan , Voortman Johannes , Wang Yonghong , Steinberg Seth M. , Funel Niccola , Meltzer Paul S. , Wang Yisong , Giaccone Giuseppe 
Published: December 2011

Abstract
Purposes: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted.
Experimental Design: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells.
Results: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G1 accumulation.
Conclusion: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer. Clin Cancer Res; 18(2); 524–33. ©2011 AACR.
Genome-Wide Association and Fine Mapping of Genetic Loci Predisposing to Colon Carcinogenesis in Mice
Authors: Liu Pengyuan , Lu Yan , Liu Hongbo , Wen Weidong , Jia Dongmei , Wang Yian , You Ming 
Published: December 2011

Abstract
To identify the genetic determinants of colon tumorigenesis, 268 male mice from 33 inbred strains derived from different genealogies were treated with azoxymethane (AOM; 10 mg/kg) once a week for six weeks to induce colon tumors. Tumors were localized exclusively within the distal colon in each of the strains examined. Inbred mouse strains exhibit a large variability in genetic susceptibility to AOM-induced colon tumorigenesis. The mean colon tumor multiplicity ranged from 0 to 38.6 (mean = 6.5 ± 8.6) and tumor volume ranged from 0 to 706.5 mm3 (mean = 87.4 ± 181.9) at 24 weeks after the first dose of AOM. AOM-induced colon tumor phenotypes are highly heritable in inbred mice, and 68.8% and 71.3% of total phenotypic variation in colon tumor multiplicity and tumor volume, respectively, are attributable to strain-dependent genetic background. Using 97,854 single-nucleotide polymorphisms, we carried out a genome-wide association study (GWAS) of AOM-induced colon tumorigenesis and identified a novel susceptibility locus on chromosome 15 (rs32359607, P = 6.31 × 10–6). Subsequent fine mapping confirmed five (Scc3, Scc2, Scc12, Scc8, and Ccs1) of 16 linkage regions previously found to be associated with colon tumor susceptibility. These five loci were refined to less than 1 Mb genomic regions of interest. Major candidates in these loci are Sema5a, Fmn2, Grem2, Fap, Gsg1l, Xpo6, Rabep2, Eif3c, Unc5d, and Gpr65. In particular, the refined Scc3 locus shows high concordance with the human GWAS locus that underlies hereditary mixed polyposis syndrome. These findings increase our understanding of the complex genetics of colon tumorigenesis, and provide important insights into the pathways of colorectal cancer development and might ultimately lead to more effective individually targeted cancer prevention strategies. Mol Cancer Res; 10(1); 66–74. ©2011 AACR.
Calcium- and integrin-binding protein 1 regulates megakaryocyte ploidy, adhesion, and migration
Authors: Kostyak John C. , Naik Meghna U. , Naik Ulhas P. 
Published: December 2011

Abstract
Megakaryocytes are large, polyploid cells that produce platelets. We have previously reported that calcium- and integrin-binding protein 1 (CIB1) regulates endomitosis in Dami cells. To further characterize the role of CIB1 in megakaryopoiesis, we used a Cib1−/− mouse model. Cib1−/− mice have more platelets and BM megakaryocytes than wild-type (WT) controls (P < .05). Furthermore, subsequent analysis of megakaryocyte-CFU production revealed an increase with Cib1 deletion compared with WT (P < .05). In addition, BM from Cib1−/− mice, cultured with thrombopoietin (TPO) for 24 hours, produced more highly polyploid megakaryocytes than WT BM (P < .05). Subsequent analysis of TPO signaling revealed enhanced Akt and ERK1/2 phosphorylation, whereas FAKY925 phosphorylation was reduced in Cib1−/− megakaryocytes treated with TPO. Conversely, platelet recovery in Cib1−/− mice after platelet depletion was attenuated compared with WT (P < .05). This could be the result of impaired adhesion and migration, as adhesion to fibrinogen and fibronectin and migration toward an SDF-1α gradient were reduced in Cib1−/− megakaryocytes compared with WT (P < .05). In addition, Cib1−/− megakaryocytes formed fewer proplatelets compared with WT (P < .05), when plated on fibrinogen. These data suggest that CIB1 plays a dual role in megakaryopoiesis, initially by negatively regulating TPO signaling and later by augmenting proplatelet production.
Novel tree-based method to generate markers from rare variant data
Authors: Jiang Yuan , Brennan Jennifer S , Calixte Rose , He Yunxiao , Nyirabahizi Epiphanie , Zhang Heping 
Published: December 2011

Abstract
Existing methods for analyzing rare variant data focus on collapsing a group of rare variants into a single common variant; collapsing is based on an intuitive function of the rare variant genotype information, such as an indicator function or a weighted sum. It is more natural, however, to take into account the single-nucleotide polymorphism (SNP) interactions informed directly by the data. We propose a novel tree-based method that automatically detects SNP interactions and generates candidate markers from the original pool of rare variants. In addition, we utilize the advantage of having 200 phenotype replications in the Genetic Analysis Workshop 17 data to assess the candidate markers by means of repeated logistic regressions. This new approach shows potential in the rare variant analysis. We correctly identify the association between gene FLT1 and phenotype Affect, although there exist other false positives in our results. Our analyses are performed without knowledge of the underlying simulating model.
Evaluation of pooled association tests for rare variant identification
Authors: Lin Wan-Yu , Zhang Boshao , Yi Nengjun , Gao Guimin , Liu Nianjun 
Published: December 2011

Abstract
Genome-wide association studies have successfully identified many common variants associated with complex human diseases. However, a large portion of the remaining heritability cannot be explained by these common variants. Exploring rare variants associated with diseases is now catching more attention. Several methods have been recently proposed for identification of rare variants. Among them, the fixed-threshold, weighted-sum, and variable-threshold methods are effective in combining the information of multiple variants into a functional unit; these approaches are commonly used. We evaluate the performance of these three methods. Based on our analyses of the Genetic Analysis Workshop 17 data, we find that no method is universally better than the others. Furthermore, adjusting for potential covariates can not only increase the true-positive proportions but also reduce the false-positive proportions. Our study concludes that there is no uniformly most powerful test among the three methods we compared (the fixed-threshold, weighted-sum, and variable-threshold methods), and their performances depend on the underlying genetic architecture of a disease.
Effect of pH on lignin analysis by Raman spectroscopy
Authors: Warsta Elina , Lähdetie Anni , Jääskeläinen Anna-Stiina , Vuorinen Tapani 
Published: December 2011

Abstract
Ultraviolet resonance Raman (UVRR) spectroscopy is a powerful tool for structural lignin analysis in situ: modification or isolation of lignin from biomass is not necessary. UVRR spectroscopy is equally applicable for samples with high lignin content and those with very low lignin content. Monomeric phenolic lignin model compounds and wood pulp samples have been studied at neutral and alkaline pH with UVRR spectroscopy. Concentration of guaiacol correlated well with the relative Raman band intensity, which indicates that lignin-containing solutions can be quantitatively measured with UVRR spectroscopy. A change in pH induced a recordable shift in the aromatic band position in the spectra, which was 25–35 cm-1 with phenolic model compounds without para substitution, 8–12 cm-1 with phenolic model compounds with para substitution, and about 2–7 cm-1 with pulp samples. No shift was detected with a non-phenolic model compound. Increasing the amount of phenolic hydroxyl groups increased the UVRR band shift in pulp samples. Additionally, increasing the pH enhanced the relative aromatic band intensity in the UVRR spectra in solution of the phenolic model compound. Accordingly, pH adjustment is relevant prior to any lignin analysis with Raman spectroscopy.
FEM Analysis of a DCP Implant on a Human Femoral Bone With a Fracture Gap
Authors: Fongsamootr T. , Bernard S. 
Published: December 2011

Abstract
Our research aims to determine the optimal screw configuration of a dynamic compressive plate (DCP) implant on a human femoral bone. The number of screws and the positioning are sensitive parameters of DCP implant stress repartition. Several previous studies have assessed the influence of thescrew configuration of a DCP implant. Using a realistic geometry of a human left femur and the finite element method (FEM), the calculations in those papers were based on a safe femoral bone. This study evaluates the influence of the application of a simulated fracture gap in the diaphyseal part on the stress repartition of the bone, plate, and screws. The main purpose is to complete the existing studies in order to provide surgeons with information on an optimal prosthesis screw configuration. The plate and screws were modeled and assembled on a cracked femoral bone. The hip region of the femur was loaded with vertical and horizontal forces. The femoral bone was cut into two parts because of the gap: the top part, close to thehip, and the bottom part, close to the knee. The FEM analysis shows that the stresses in screws located in the top part of the femoral bone had significantly increased, whereas the stresses on the plate and the bone had been reduced.
Attempt at Quantification of Surface Degradation and Evaluation of Relationship between Outdoor and Accelerated Exposure of Construction Sealants
Authors: Enomoto Noriyoshi , Ito Akihiko , Tanaka Kyoji 
Published: December 2011

Abstract
The weatherability of construction sealants is a highly important performance criterion for the prediction of their service lives. Currently, the evaluation of a sealant’s surface weatherability is carried out mainly via qualitative visual judgment. One objective of this paper is to establish a quantitative method for the assessment of surface degradation. A further objective is the evaluation of the relationship between outdoor and accelerated exposure with regard to surface degradation. The understanding of this relationship is important for the shortening of the development cycle and the prediction of a sealant’s service life. The paper presents information on the weatherability of construction sealants based on a recently developed test specimen design that allows simultaneous exposure of the sealant to forced compression and extension movement in a single specimen with cyclic movement and weathering carried out simultaneously. A quantitative method for the assessment of surface cracks is employed, and the relationship between outdoor and accelerated weathering exposure is evaluated by using metrics that indicate the degree of surface cracking as a new semi-quantitative criterion of surface degradation.
Von modellbasierten Storyboards zu kontextsensitiven Interaction-Cases
Authors: Kühn Romina , Keller Christine , Schlegel Thomas 
Published: December 2011

Zusammenfassung
Storyboarding als Analyseinstrument und Prototyping-Methode für das ”User-Centered Design“ etabliert sich aufgrund der Einfachheit, bildliche Darstellungen zu erstellen und zu verstehen. Da in ubiquitären Umgebungen oftmals sehr komplexe Interaktionen stattfinden, die zusätzlich stark vom Kontext beeinflusst werden, stellen modellgestützte Storyboards eine gute Möglichkeit dar, ubiquitäre interaktive Systeme zu modellieren. Detaillierte Interaktionsabläufe können mit Hilfe von Interaction-Cases aus den Storyboards abgeleitet werden. In dieser Arbeit wird eine Methode vorgestellt, wie anhand von Storyboards Kontext für kontextsensitive ubiquitäre Systeme identifiziert und in kontextadaptive Interaction-Cases überführt werden kann. Dazu werden Ergebnisse einer Benutzerbefragung herangezogen.
Ein UML-basierter Ansatz für die modellgetriebene Generierung grafischer Benutzungsschnittstellen
Authors: Honold Frank , Schüssel Felix , Weber Michael 
Published: December 2011

Zusammenfassung
Die Erstellung der Benutzungsschnittstelle nimmt mittlerweile einen großen Teil im Entwicklungsprozess ein. Je komplexer Anwendungen werden, desto zeit- und kostenintensiver wird es, geeignete Oberflächen zu erstellen. Eine automatisierte Lösung könnte hier Abhilfe schaffen. Vorhandene Techniken bieten maximal eine Teilautomatisierung und sind zudem nicht in den Arbeitsprozess der Entwickler ohne Störungen einzubinden, da sie oftmals eigene Modellierungssprachen voraussetzen. Der hier vorgestellte Ansatz basiert auf dem Cameleon Reference Framework und verwendet als Ausgangsbasis für die Generierung die UML. So kann das Verfahren ohne aufwendiges Einarbeiten angewendet werden. GUIs für unterschiedliche Zielplattformen können automatisch aus UML-Diagrammen erzeugt werden. Durch den Einsatz von Beautifications ist es zudem möglich, wiederverwendbare Anpassungen der Oberflächen zu erstellen und so Expertenwissen bezüglich Interaktion und Gestaltung einzubringen.
Automatiserte Generierung von WIMP-UIs basierend auf Kommunikationsmodellen
Authors: Falb Jürgen , Kaindl Hermann , Popp Roman , Raneburger David 
Published: December 2011

Zusammenfassung
Manuelles Erstellen von User Interfaces (UIs) ist teuer und zeitaufwändig, insbesondere für UIs, die auf mehreren Endgeräten mit verschiedenen Eigenschaften (z.B. Größe bzw. Auflösung des Bildschirms) ablaufen sollen. Etwa sind Webseiten, die für PCs konzipiert wurden, oft nur schlecht auf einem Smartphone zu bedienen. Daher wird es im Allgemeinen für gute Bedienbarkeit nötig sein, verschiedene UIs für verschiedene Geräte zu erstellen. Eine Möglichkeit zur Verbesserung ist die automatisierte Generierung von UIs aus Modellen mit hoher Abstraktion. Dies sind meist Task-basierte Modelle. Wir definieren hingegen Kommunikationsmodelle zur Spezifikation kommunikativer Interaktion durch Diskurse im Sinne von (Klassen von) Dialogen. Ähnlich wie bei einigen Task-basierten Ansätzen verwenden auch wir automatisierte Modell-Transformationen in immer konkretere Modelle und letztlich Code für die UIs. Unser Ansatz zeichnet sich allerdings durch Optimierungen aus, die automatisch für gegebene Geräte-Spezifikationen erfolgen. Konkret ergeben sich dadurch sogar spezielle Anpassungen für verschiedene Smartphones (iPhone vs. Android-basierte Geräte).
User Experience Monitoring: Über die Notwendigkeit geschäftskritische Online-Prozesse permanent zu überwachen
Authors: Hartmann Juliane 
Published: December 2011

Zusammenfassung
Das Konzept der User Experience erfreut sich in Forschung und Praxis anhaltend großer Beliebtheit und ist in Online-Prozessen zu einem zentralen Baustein für den langfristigen Erfolg eines Webangebots geworden. User Experience Monitoring ermöglicht es – anders als es durch etablierte Tools oder bekannte Messinstrumente geschieht – die User Experience eines Online-Prozesses permanent zu überwachen. So wird es möglich, Veränderungen im Nutzungsverhalten genau nachzuvollziehen und den Erfolg von Website-Optimierungsmaßnahmen direkt zu kontrollieren. Geschäftskritische Prozesse (z.B. Buchungs-, Kauf- oder Registrierungsprozesse) können so um ein Vielfaches schneller und effizienter als bisher möglich visualisiert, analysiert und optimiert werden.
Musikhören und Arbeiten im Einklang
Authors: Chien Wei-Chi , Hassenzahl Marc , Mehnert Kurt 
Published: December 2011

Zusammenfassung
Musik macht vieles leichter. Auch während geistiger Arbeit am Schreibtisch schätzen viele Menschen Musik, als ein Mittel zur Motivation und gegen das Gefühl des Alleinseins. Wenn die Musik allerdings zu viel Aufmerksamkeit bindet, kann dies die Konzentration stören. Der vorliegende Beitrag beschreibt die Gestaltung eines Konzepts, das den Einklang von Musikhören und geistiger Arbeit unterstützt, indem es die Bindung von Aufmerksamkeit durch die Musik steuerbar macht und es so erlaubt, Musik an die kognitiven Anforderungen der Arbeitsaufgabe anzupassen. Im Vordergrund des Gestaltungsprozesses standen das zu erzeugende Erlebnis und die damit verbundenen Bedürfnisse der Nutzer. Die Interaktion und die formale Gestaltung wurden aus diesem Erlebnis abgeleitet.
High prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus despite different hormonal profiles
Authors: Samara-Boustani Dinane , Colmenares Ana , Elie Caroline , Dabbas Myriam , Beltrand Jacques , Caron Virgile , Ricour Claude , Jacquin Paul , Tubiana-Rufi Nadia , Levy-Marchal Claire , Delcroix Christine , Martin Delphine , Benadjaoud Lila , Jacqz Aigrain Evelyne , Trivin Christine , Laborde Kathleen , Thibaud Elisabeth , Robert Jean-Jacques , Polak Michel 
Published: December 2011

ObjectivesTo compare the pubertal development, the hormonal profiles and the prevalence of hirsutism and menstrual disorders in obese adolescent girls and adolescent girls with type 1 diabetes mellitus (T1DM).MethodsData were collected from 96 obese adolescent girls and 78 adolescent girls with T1DM at Tanner stage IV or V, whose ages ranged between 11.9 and 17.9 years.ResultsHigh prevalence of hirsutism and menstrual disorder was found in the obese adolescent girls (36.5 and 42% respectively) and the adolescent girls with T1DM (21 and 44% respectively). The obese girls were significantly younger at pubarche, thelarche and menarche than the girls with T1DM. Hirsutism in the obese girls and those with T1DM was associated with hyperandrogenaemia and a raised free androgen index (FAI). When the cause of the raised FAI was investigated in both the groups of girls with hirsutism, the raised FAI in the obese girls was due to low serum sex hormone-binding globulin (SHBG) levels. In contrast, the raised FAI of the girls with T1DM and hirsutism was due to hyperandrogenaemia. Menstrual disorders in the T1DM girls were associated also with hyperandrogenaemia unlike obese girls.ConclusionsHirsutism and menstrual disorders are common in obese adolescent girls and adolescent girls with T1DM. Although hyperandrogenaemia is present in both groups of girls, the androgenic profiles of the two groups differ. The hyperandrogenaemia in the obese girls is primarily due to their decreased serum SHBG levels, whereas the hyperandrogenaemia in the girls with T1DM is due to their increased androgen production.
Dimensional Change of Elastomeric Materials after Immersion in Disinfectant Solutions for Different Times
Authors: Carvalhal Cintia Iara Oda , de Mello José Antônio Nunes , Sobrinho Lourenço Correr , Correr Américo Bertolazzo , Sinhoreti Mário Alexandre Coelho 
Published: December 2011

ABSTRACT

Aim
The aim of this study was to evaluate the influence of immersion period in two disinfectant solutions on dimensional change of four elastomeric impression materials.

Materials and methods
Four representative materials of each class of elastomers: Xantopren (polydimethylsiloxane—PDS), Express (polyvinyl siloxane—PVS); Permlastic (polysulfide— PS) and Soft Impregum (polyether—EP) were mixed according to manufacturers’ instructions and then inserted into a metal matrix prepared according to the specification of ISO 4823. The molds were removed from the matrix after 7 minutes and immersed in disinfectant solutions (sodium hypochlorite 0.5 and 2% glutaraldehyde) for 5, 10, 20, 30 and 60 minutes (n = 7), except the control group, which was not immersed. Once removed from solutions, the test samples were washed in water for 15 seconds, dried and measured three times, using a comparative optical microscope, with accuracy of 0.0005 mm. The analysis of variance with three criteria and Tukey's test with significance level of 5% showed that differences in linear dimensions of the materials analyzed were not statistically significant (p > 0.05) after soaking in sodium hypochlorite 0.5 and 2% glutaraldehyde, for the tested periods of time.

Clinical significance
Combinations of molding material and disinfecting solution can be used in the dental clinic for infection control, without changing the dimensional molds, for immersion periods not longer than 20 minutes.

How to cite this article
Carvalhal CIO, de Mello JAN, Sobrinho LC, Correr AB, Sinhoreti MAC. Dimensional Change of Elastomeric Materials after Immersion in Disinfectant Solutions for Different Times. J Contemp Dent Pract 2011;12(4): 252-258.