bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4017: Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues
Authors: Martin Eric , Malgor Ramiro , Goetz Douglas , Burdick Monica 
Published: May 2015

Abstract
Accumulating evidence suggests that selectin/selectin ligand interactions are involved in mediating the adhesion of bloodborne circulating tumor cells at distant sites during the later stages of cancer metastasis. Presently, immunostaining is the standard method for detecting selectin ligands expressed on tissue, but this approach cannot ascertain if the selectin ligands are functional. That is, detection of purported selectin ligands by static (no-force) immunostaining under equilibrium conditions does not necessitate that the reactive antigens are able to mediate cell adhesion with hemodynamic flow (force) under non-equilibrium conditions. The relevance of functional selectin ligands as a biomarker is presently unclear because of the lack of adequate detection methods. Recently, we developed a method to detect functional selectin ligands in situ by perfusing selectin-coated microspheres (probes) over cancer tissues in a microfluidic device. This method of tissue interrogation is termed dynamic biochemical tissue analysis (DBTA). Preliminary analysis of signet ring cell colon carcinoma tissue revealed the highest amount of specific probe adhesion relative to negative control probes occurred with a murine E-selectin probe, rather than human E-, P-, or L-selectin probes. Therefore, to investigate the relevance of functional selectin ligand expression on cancer tissue as a biomarker, 196 cases of various solid tumors at primary and metastatic sites were investigated with DBTA using murine E-selectin. Probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, prostate, and stomach cancers, demonstrating the presence of functional selectin ligands. In addition, probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, rectal, and stomach cancer tissues sampled from metastatic sites. Overall, probe adhesion levels for the tissues investigated ranged from 10 specifically adherent probes/mm2 on lung adenosquamous carcinoma to 1170 specifically adherent probes/mm2 on ovarian endometrioid adenocarcinoma, indicating broad levels of functional selectin ligand expression. In summary, DBTA detects functional selectin ligands expressed on tissue from multiple cancer types at both the primary and metastatic sites, data that may provide valuable diagnostic and prognostic information for malignant tumors.
Citation Format: Eric Martin, Ramiro Malgor, Douglas Goetz, Monica Burdick. Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4017. doi:10.1158/1538-7445.AM2014-4017
Abstract 402: Tumor necrosis factor-alpha and apoptosis induction in melanoma cells through histones modification by 3-deazaneplanocin A
Authors: Tanaka Ryo , Donovan Nicholas , Yu Qiang , Irie Reiko , Hoon Dave S.B. 
Published: May 2015

Abstract
Tumor necrosis factor-alpha (TNFα) is cytokine, which influences the tumor microenvironment. While melanoma is known to express variable levels of TNFα, its regulation is not well understood. The objective of the study was to investigate the epigenetic regulation of TNFα in melanoma cells. Melanoma cell lines were treated with 3-Deazaneplanocin A(DZNep), an inhibitor of polycomb-repressive complex 2(PRC2), and analyzed for its effect on the cell viability assay and apoptosis assay. PRC2 and histones H3K27me3, H3K4me2 and H3K9ac activity were assessed pre- and post-DZNep by Western blot on cell lines and tumors. ChIP-qPCR array, chromatin immunoprecipitation, and PCR array analysis of melanoma lines treated with DZNep. DZNep could induce apoptosis in melanoma cells, and up-regulate TNFα expression. Specific histones were associated with the upregulation of TNFα expression by ChIP-qPCR array. The repressive histone mark, H3K27me3, as well as the active histone marks, H3K4me2 and H3K9ac, were correlated with the regulation of TNFα expression. We demonstrated that DZNep can activate TNFα expression in melanoma through histone modification. These findings suggest that epigenetic agents targeting PRC2 can activate TNFα in melanoma cells. The DNA methylation, H3K27me3, H3K4me2, and H3K9ac modification, contribute to TNFα regulation.
Citation Format: Ryo Tanaka, Nicholas Donovan, Qiang Yu, Reiko Irie, Dave S.B. Hoon. Tumor necrosis factor-alpha and apoptosis induction in melanoma cells through histones modification by 3-deazaneplanocin A. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 402. doi:10.1158/1538-7445.AM2014-402
Abstract 4035: A mitochondrial switch promotes tumor metastasis
Authors: Porporato Paolo E. , Payen Valéry L. , Pérez-Escuredo Jhudit , Danhier Pierre , Feron Olivier , Gallez Bernard , Sonveaux Pierre 
Published: May 2015

Abstract
Cancers evolve a subpopulation of tumor cells that metabolically rely on glycolysis uncoupled from oxidative phosphorylation irrespectively of oxygen availability (aerobic glycolysis). Given that most metastases are abnormally avid for glucose (which is the rationale for their clinical detection using FDG-PET) and because clinical data show a positive correlation between lactate production and tumor metastasis, we reasoned that cells performing aerobic glycolysis could constitute a population of metastatic progenitor cells that would remain glycolytic in the blood stream. We found a different metabolic phenotype, though. Indeed, using serial rounds of in vitro selection of highly invasive tumor cells (starting from wild-type SiHa human cervix adenocarcinoma cells) and in vivo selection of supermetastatic tumor cells (starting from B16-F10 mouse melanoma cells), we identified a mitochondrial switch corresponding to an overload of the TCA cycle with preserved mitochondrial functions (including ATP production) but increased mitochondrial superoxide production. The switch provided a metastatic advantage which was phenocopied by moderate OXPHOS inhibition associated with mild mitochondrial superoxide increase. Thus, two different events, OXPHOS overload or moderate OXPHOS inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis; demonstrating the central role of mitochondrial superoxide generation in the pathogenesis of metastasis. Consequently, we report that mitochondria-specific superoxide scavenging (using mitoTEMPO or mitoQ) inhibits metastatic dissemination from primary mouse and human tumors, which opens a new avenue for the therapeutic prevention of tumor metastasis.
Citation Format: Paolo E. Porporato, Valéry L. Payen, Jhudit Pérez-Escuredo, Pierre Danhier, Olivier Feron, Bernard Gallez, Pierre Sonveaux. A mitochondrial switch promotes tumor metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4035. doi:10.1158/1538-7445.AM2014-4035
Abstract 4048: GFRα1 is required for GDNF-induced viability, migration, and signaling through RET in breast cancer cells
Authors: Ferrante Catherine A. , DeAngelis Nikki , Verona Raluca 
Published: May 2015

Abstract
Hormone resistance is a major challenge in treating breast cancer patients. Although anti-estrogens, such as tamoxifen, are initially successful controlling disease in estrogen receptor alpha positive (ERα+) tumors, patients with metastatic disease and as many as 40 % of patients receiving adjuvant tamoxifen acquire resistance to treatment, relapse, and die. The receptor tyrosine kinase, RET, its co-receptor, GFRα1, and their ligand, GDNF, are proteins that are emerging as potential contributors to hormone resistance in breast cancer. RET and GFRα1 were recently shown to be overexpressed in a subset of ERα+ breast cancer tumors, and GFRα1 expression was associated with lymphovascular invasion. In vitro, silencing RET with siRNA increased MCF7 cells' sensitivity to tamoxifen and, in the absence of estrogens, treatment of MCF7 cells with GDNF induced upregulation of ERα target genes. Additionally, GDNF stimulation of MCF7 cells enhanced proliferation, survival, and cell scattering. Together, clinical and preclinical data suggest that this pathway plays an important role in driving breast cancer invasion, metastasis, and hormone resistance. However, the role of GFRα1 has not been examined in tumor cell invasion and metastasis. In this study we tested the functional consequences of silencing GFRα1 in ERα + MCF7 cells on tumor cell migration, invasion, and RET signaling. We showed that targeted reduction of GFRα1 significantly inhibited GDNF-induced migration in both a transwell (p=&lt;0.001) and scratch wound assay (p=&lt;0.001 at 24 hours). In addition, GDNF-induced increases in viability were significantly decreased when MCF7 cells were treated with neutralizing antibodies against GFRα1 (p=&lt;0.001). Silencing GFRα1 in GDNF-treated MCF7 cells led to reduced invasion through collagen I, although this difference was not significant. Lastly, siRNA targeted reduction of GFRα1 in MCF7 cells inhibited GDNF-induced phosphorylation of RET. Together the data demonstrate that GFRα1 is important in migration and cell viability as well as RET signaling in breast cancer cells.
Citation Format: Catherine A. Ferrante, Nikki DeAngelis, Raluca Verona. GFRα1 is required for GDNF-induced viability, migration, and signaling through RET in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4048. doi:10.1158/1538-7445.AM2014-4048
Abstract 4068: Overexpression of anillin in colorectal cancer promotes the cell proliferation, cell mobility and cell invasion
Authors: Chuang Hui Y. , Ou Yu Hsuan 
Published: May 2015

Abstract
Colorectal cancer (CRC) is the third most prevalent cancer in the developed countries, accounting for more than 50,000 cancer deaths per year. We used microarray to analyze gene expression in patients with different stages of colorectal cancer. Among the 157 metastasis-related genes, RT-PCR and quantitative real-time PCR (qPCR) were used to verify 11 genes. The roles of anillin (ANLN), one of 11 metastasis-associated genes, in colorectal cancer are not clear. Therefore, we focused on ANLN in this study. We found that the expression levels of anillin are higher in tumor specimens, even in metastasis tumor grade compared with those of adjacent normal tissues by real-time PCR. In order to understand the roles of anillin in tumorigenesis and metastasis of colorectal cancer, we used anillin overexpressed HT29 and shRNA-knockdowned SW480. Our data indicated that anillin overexpressed HT29 showed faster replication kinetics probably due to prolonged G2/M phase. Next, we found that the number and size of colony were increased in anillin over expressed cells in soft agar assay suggesting a role of anillin in tumorgenesis of colorectal cancer. Notably, anillin overexpressed SW480 and HT29 lines demonstrated increased migration and invasion. This increased mobility in anillin overexpressed SW480 and HT29 lines partially correlated with reduced E-cadherin levels. By confocal analysis of philloidin stained cells, we also found increased F-actin bundles accumulation in anillin overexpressed HT29 cells. We hypothesize that anillin may promote partial EMT and cell migration through induced cytoskeleton remodeling. Taken together, we suggest that anillin is involved in enhancement of proliferation, mobility, invasion of colorectal cancer cell lines, which may lead to enhanced tumorgenesis and metastasis potential.
Citation Format: Hui Yu Chuang, Yu Hsuan Ou. Overexpression of anillin in colorectal cancer promotes the cell proliferation, cell mobility and cell invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4068. doi:10.1158/1538-7445.AM2014-4068
Tumoricidal Effects of Macrophage-Activating Immunotherapy in a Murine Model of Relapsed/Refractory Multiple Myeloma
Authors: Jensen Jeffrey Lee , Rakhmilevich Alexander , Heninger Erika , Broman Aimee Teo , Hope Chelsea , Phan Funita , Miyamoto Shigeki , Maroulakou Ioanna , Callander Natalie , Hematti Peiman , Chesi Marta , Bergsagel P. Leif , Sondel Paul , Asimakopoulos Fotis 
Published: May 2015

Abstract
Myeloma remains a virtually incurable malignancy. The inevitable evolution of multidrug-resistant clones and widespread clonal heterogeneity limit the potential of traditional and novel therapies to eliminate minimal residual disease (MRD), a reliable harbinger of relapse. Here, we show potent anti-myeloma activity of macrophage-activating immunotherapy (αCD40+CpG) that resulted in prolongation of progression-free survival (PFS) and overall survival (OS) in an immunocompetent, preclinically validated, transplant-based model of multidrug-resistant, relapsed/refractory myeloma (t-Vκ*MYC). αCD40+CpG was effective in vivo in the absence of cytolytic natural killer, T, or B cells and resulted in expansion of M1-polarized (cytolytic/tumoricidal) macrophages in the bone marrow. Moreover, we show that concurrent loss/inhibition of Tpl2 kinase (Cot, Map3k8), a MAP3K that is recruited to activated CD40 complex and regulates macrophage activation/cytokine production, potentiated direct, ex vivo anti-myeloma tumoricidal activity of αCD40+CpG–activated macrophages, promoted production of antitumor cytokine IL12 in vitro and in vivo, and synergized with αCD40+CpG to further prolong PFS and OS in vivo. Our results support the combination of αCD40-based macrophage activation and TPL2 inhibition for myeloma immunotherapy. We propose that αCD40-mediated activation of innate antitumor immunity may be a promising approach to control/eradicate MRD following cytoreduction with traditional or novel anti-myeloma therapies. Cancer Immunol Res; 3(8); 881–90. ©2015 AACR.
Crença, razão e entendimento segundo o realismo de F. H. Jacobi
Authors: Leite Thiago Magalhães 
Published: May 2015

<p>F. H. Jacobi permanece uma figura controversa na história da filosofia. Mesmo substancialmente presente nos debates que seguiram à publicação da <em>Crítica da Razão Pura</em>, sendo um dos mais radicais críticos da <em>Crítica</em>, Jacobi segue como uma figura de fundo, como se o seu ponto de vista não viesse de um corpo filosófico próprio. Entretanto, um olhar atento a suas obras mostra o contrário. Razão e entendimento, lógica e os fundamentos da ciência, são reconsiderados sob uma nova luz: a <em>crença </em>é a base de todo conhecimento, e nesse sentido a própria ciência é um saber de “segunda mão”. Gostaríamos aqui de apresentar tais conceitos e mostrar a maneira pela qual eles se voltam contra o idealismo crítico. <strong></strong></p>
A estrutura básica como objeto da justiça: liberdades básicas e as bases sociais do autorrespeito
Authors: Werle Denílson Luis 
Published: May 2015

<p>O artigo parte do pressuposto de que para fazer um diagnóstico das injustiças, vulnerabilidades e carências das pessoas uma teoria crítica da justiça deve tomar como ponto de partida a posição real das pessoas no mundo, seus contextos de socialização e suas relações sociais de interdependência. Para isso, o objeto primário de uma teoria da justiça não deve ser diretamente os indivíduos e suas capacidades, mas sim a estrutura básica da sociedade, formada pelas principais instituições sociais, econômicas e políticas, isto é, os contextos intersubjetivos das relações interpessoais de cooperação social e de socialização que são determinantes na vida concreta das pessoas e principalmente na realização igual de suas liberdades e na formação do sentido interno do que significa ser autônomo.</p>
Return to Work in Out-of-Hospital Cardiac Arrest Survivors
Authors: Kragholm Kristian , Wissenberg Mads , Mortensen Rikke Normark , Fonager Kirsten , Jensen Svend Eggert , Rajan Shahzleen , Lippert Freddy Knudsen , Christensen Erika Frischknecht , Hansen Poul Anders , Lang-Jensen Torsten , Hendriksen Ole Mazur , Kober Lars , Gislason Gunnar , Torp-Pedersen Christian , Rasmussen Bodil Steen 
Published: May 2015

Background—
Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors.

Methods and Results—

In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001–2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18–65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1–3, 46–59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1–3, 1–19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001–2005 versus 78.1% in 2006–2011;
P
=0.002). In multivariable Cox regression analysis, factors associated with return to work with ≥6 months of sustainable employment were as follows: (1) arrest during 2006–2011 versus 2001–2005, hazard ratio (HR), 1.38 (95% CI, 1.05–1.82); (2) male sex, HR, 1.48 (95% CI, 1.06–2.07); (3) age of 18 to 49 versus 50 to 65 years, HR, 1.32 (95% CI, 1.02–1.68); (4) bystander-witnessed arrest, HR, 1.79 (95% CI, 1.17–2.76); and (5) bystander cardiopulmonary resuscitation, HR, 1.38 (95% CI, 1.02–1.87).

Conclusions—
Of 30-day survivors employed before arrest, 76.6% returned to work. The percentage of survivors returning to work increased significantly, along with improved survival during 2001–2011, suggesting an increase in the proportion of survivors with preserved function over time.
Effect of Turbulence Parameterization on Assessment of Cloud Organization
Authors: Machado Luiz A. T. , Chaboureau Jean-Pierre 
Published: May 2015

Abstract
This study evaluates the cloud and rain cell organization in space and time as forecasted by a cloud-resolving model. The forecast fields, mainly describing mesoscale convective complexes and cold fronts, were utilized to generate synthetic satellite and radar images for comparison with Meteosat Second Generation and S-band radar observations. The comparison was made using a tracking technique that computed the size and lifetime of cloud and rain distributions and provided histograms of radiative quantities and cloud-top height. The tracking technique was innovatively applied to test the sensitivity of forecasts to the turbulence parameterization. The simulations with 1D turbulence produced too many small cloud systems and rain cells with a shorter lifetime than observed. The 3D turbulence simulations yielded size and lifetime distributions more consistent with the observations. As shown for a case study, 3D turbulence yielded longer mixing length, larger entrainment, and stronger turbulence kinetic energy inside clouds than 1D turbulence. The simulation with 3D turbulence had the best scores in high clouds. These features suggest that 1D turbulence did not produce enough entrainment, allowing the formation of more small cloud and rain cells than observed. Further tests were performed on the sensitivity to the mixing length with 3D turbulence. Cloud organization was very sensitive to in-cloud mixing length and the use of a very small value increased the number of small cells, much more than the simulations with 1D turbulence. With a larger in-cloud mixing length, the total number of cells, mainly the small ones, was strongly reduced.
Relationship of resting heart rate and physical activity with insulin sensitivity in a population-based survey
Authors: Grandinetti Andrew , Liu David MKI , Kaholokula Joseph Keawe‘aimoku 
Published: May 2015

Abstract
Background
Resting heart rate (RHR) has been identified as an independent risk factor for cardiovascular disease and mortality, contributing to atherosclerosis, the progression of heart failure, and myocardial ischemia and infarction. This study examines the association RHR and physical activity has with insulin resistance and insulin secretion in a multiethnic cohort from North Kohala, Hawai‘i.

Methods
Cross-sectional data from 1,440 participants of Native Hawaiian, Japanese, Filipino, Caucasian, and mixed ethnic ancestries were analyzed for the study to include anthropometric measurements, and biochemical markers. Body fat was estimated by calculating body mass indices (BMI); body fat distribution by waist-hip ratios (WHR); and fasting plasma glucose and insulin levels were used to calculate insulin resistance using the Homeostasis Model (HOMA-IR). First phase insulin response was estimated using the insulin secretion ratio (ISR). Associations were estimated using general linear models (GLM).

Results
Caucasians had lower mean RHR than all other ethnic groups; there were no statistically significant differences between other ethnic groups on mean RHR. HOMA-IR was associated with ethnic group, BMI and WHR, PA and RHR, while ISR was associated with age, ethnic group and BMI, but none of the primary risk factors. Both RHR and physical activity level remained significant for insulin resistance.

Conclusions
In a multiethnic cohort from a rural community in Hawai‘i, increased RHR and a lower level of physical activity were both independently associated with increased risk for the development of insulin resistance, suggesting cardiovascular fitness may be as important as physical activity in preventing insulin resistance.
A calculator for Roche lobe properties
Authors: Leahy Denis A , Leahy Janet C 
Published: May 2015

Abstract
Background
The Roche lobe geometry is important to understand and study the properties of the mass-losing component in a semi-detached binary system. However it is not easy to calculate accurately, and existing tables usually do not include the parameters of the binary system under study, nor do they allow for non-synchronous rotation.

Results
A calculator for properties of the Roche lobe is presented in two formats. An easy-to-use Java version has a graphic interface, and a Fortran 90 version has a command line interface. The Fortran version allows for easy modifications by the user. Both versions have two basic output options: one provides values of a set of various quantities (such as the Lagrange points along the binary axis, and area and volume of the Roche lobe); the second provides $R(\theta,\phi)$
R
(
θ
,
ϕ
)
, the distance from the stellar center to the stellar surface for any specified polar angle. A single set of input parameters can be entered directly or a large set of input parameters can be specified in a text file. The calculator includes the options to have non-synchronous rotation of the star, or to have the star underfill its Roche lobe. It can be used to calculate Roche lobe properties for the case of elliptical orbits, with some restrictions.

Conclusions
We present a convenient software tool for quickly and accurately calculating Roche lobe properties for mass ratio in the range 0.01 to 100, for Roche lobe fill-out factor in the range 0.1 to 1.0, and for dimensionless rotation rate of the star in the range 0.1 to 2.0. This will allow anyone working with a binary star system to obtain the Roche lobe or stellar surface geometry for their system.