bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the Mechanisms of Tumorigenesis in Human Pancreatic Ductal Epithelial Cells
Authors: Chang Zhe , Li Zhongkui , Wang Xiaoyang , Kang Ya'an , Yuan Yuhui , Niu Jiangong , Wang Huamin , Chatterjee Deyali , Fleming Jason B. , Li Min , Abbruzzese James L. , Chiao Paul J. 
Published: January 2013

Abstract
Purpose: The most common genetic lesions in pancreatic ductal adenocarcinoma (PDAC) have been identified. However, significant gaps still exist in our understanding of how such genetic alterations act in concert to induce PDAC development. In this study, we investigated the mechanism of tumorigenic transformation in the immortalized human pancreatic ductal epithelial (HPDE) cell line by sequentially introducing PDAC signature alterations into this cell line.
Experimental Design: The phenotype for stable expression of mutant K-ras, Her2, p16/p14shRNA, and Smad4shRNA in HPDE cells was examined by assays for cell proliferation, migration, invasion, soft agar, and orthotopic tumorigenesis. The mechanisms of tumorigenic transformation were further explored by gene expression profiling and pathway analyses.
Results: The transformed cells exhibited enhanced proliferation, migration, and invasion, displayed anchorage-independent growth in soft agar, and grew orthotopic tumors with some histopathologic features of PDAC. We found that Smad4 played key roles in the tumorigenic transformation of HPDE cells. We further found that MDM2 and Bmi-1 were overexpressed in the tumorigenic HPDE cells and that Bmi-1 overexpression was regulated by Smad4. Ingenuity Pathway Analysis software analysis of microarray data revealed that dysregulation of integrin-linked kinase signaling and the cell cycle were the most significant changes involved in tumorigenic transformation. Altogether, this cell culture model closely recapitulated human pancreatic carcinogenesis from gene lesions, activation of specific signaling pathways, and some histopathologic features.
Conclusion: The combination of activated K-ras and Her2 with inactivated p16/p14 and Smad4 was sufficient and essential to transform HPDE cells, thus revealing the potential tumorigenic mechanism. Clin Cancer Res; 19(3); 549–59. ©2012 AACR.
Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer
Authors: Horak Christine E. , Pusztai Lajos , Xing Guan , Trifan Ovidiu C. , Saura Cristina , Tseng Ling-Ming , Chan Stephen , Welcher Rosanne , Liu David 
Published: January 2013

Abstract
Purpose: Predictive biomarkers offer the potential to improve the benefit:risk ratio of a therapeutic agent. Ixabepilone achieves comparable pathologic complete response (pCR) rates to other active drugs in the neoadjuvant setting. This phase II trial was designed to investigate potential biomarkers that differentiate response to this agent.
Experimental Design: Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received neoadjuvant doxorubicin/cyclophosphamide, followed by 1:1 randomization to ixabepilone (n = 148) or paclitaxel (n = 147). Rates of pCR were compared between treatment arms based on predefined biomarker sets: TUBB3, TACC3, and CAPG gene expression, a 20- and 26-gene expression model, MDR1 protein expression, and other potential markers of sensitivity. βIII-tubulin protein expression is reported separately but is referred to here for completeness. All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis before chemotherapy. Gene expression profiling data were used for molecular subtyping.
Results: There was no significant difference in the rate of pCR in both treatment arms in βIII-tubulin–positive patients. Higher pCR rates were observed among βIII-tubulin–positive patients than in βIII-tubulin–negative patients. Furthermore, no correlation was evident between TUBB3, TACC3, and CAPG gene expression, MDR1 protein expression, multi-gene expression models, and the efficacy of ixabepilone or paclitaxel, even within the estrogen receptor–negative subset.
Conclusion: These results indicate that βIII-tubulin protein and mRNA expression, MDR1 protein expression, TACC3 and CAPG gene expression, and multigene expression models (20- and 26-gene) are not predictive markers for differentiating treatment benefit between ixabepilone and paclitaxel in early-stage breast cancer. Clin Cancer Res; 19(6); 1587–95. ©2013 AACR.
Germany’s Different: Protest, Hegemony, and the European Crisis
Authors: Kaindl Christina 
Published: January 2013

Abstract
The uprising of the Indignados, Democracia Real Ya! and the Occupy movement have brought back protest all over Europe in 2011. In Germany—despite several tens of thousands of people showing up for the international action day on October 15th, the situation has been different. After some demonstrations in 2009 and 2010 organized on a platform of “We won’t pay for your crisis,” there had been mostly smaller local manifestations not backed by broader alliances. This changed with the Blockupy-Frankfurt protests at the end of May 2012 that called for European action days to shut down the financial district. But attempts to include the big unions into alliances opposing the crisis politics of the government have failed; and the women’s movement has been basically non-existent in Germany for about two decades. I will try to shed some light on how the general weakness of the movement is related to the strategies of integration into neo-liberal governance.
Dealing with Disasters in an Age of Globalized Sentiment: Testing the Boundaries of the Cosmopolitan Ideal?
Authors: O’Byrne Darren 
Published: January 2013

AbstractNatural disasters, such as the Japanese earthquake and tsunami of March 2011, have not only tested the fragility of the world capitalist system, but have asked questions of the ‘cosmopolitan ideal’ that underpins the discourse on global civil society prevalent in much literature on globalization. In this article I consider why the global response to such tragedies is markedly different to the more muted response to more overtly political tragedies, such as atrocities committed by states, and suggests that what it demonstrates is not a full cosmopolitanismper se, but a ‘selective cosmopolitanism’ grounded in a ‘de-politicization of feeling’. As a result, the political context of these natural disasters is often ignored and this calls for a repositioning of such disasters within a human rights framework and for an analysis of them informed by a critical globalization studies.
TGFβ signaling regulates lipogenesis in human sebaceous glands cells
Authors: McNairn Adrian J , Doucet Yanne , Demaude Julien , Brusadelli Marion , Gordon Christopher B , Uribe-Rivera Armando , Lambert Paul F , Bouez Charbel , Breton Lionel , Guasch Géraldine 
Published: January 2013

Abstract

Background
Sebaceous glands are components of the skin essential for its normal lubrication by the production of sebum. This contributes to skin health and more importantly is crucial for the skin barrier function. A mechanistic understanding of sebaceous gland cells growth and differentiation has lagged behind that for keratinocytes, partly because of a lack of an in vitro model that can be used for experimental manipulation.

Methods
We have developed an in vitro culture model to isolate and grow primary human sebocytes without transformation that display functional characteristics of sebocytes. We used this novel method to probe the effect of Transforming Growth Factor β (TGFβ) signaling on sebocyte differentiation, by examining the expression of genes involved in lipogenesis upon treatment with TGFβ1. We also repressed TGFβ signaling through knockdown of the TGFβ Receptor II to address if the effect of TGFβ activation is mediated via canonical Smad signal transduction.

Results
We find that activation of the TGFβ signaling pathway is necessary and sufficient for maintaining sebocytes in an undifferentiated state. The presence of TGFβ ligand triggered decreased expression in genes required for the production of characteristics sebaceous lipids and for sebocyte differentiation such as FADS2 and PPARγ, thereby decreasing lipid accumulation through the TGFβ RII-Smad2 dependent pathway.

Conclusion
TGFβ signaling plays an essential role in sebaceous gland regulation by maintaining sebocytes in an undifferentiated state. This data was generated using a novel method for human sebocyte culture, which is likely to prove generally useful in investigations of sebaceous gland growth and differentiation. These findings open a new paradigm in human skin biology with important implications for skin therapies.
C3G forms complexes with Bcr-Abl and p38α MAPK at the focal adhesions in chronic myeloid leukemia cells: implication in the regulation of leukemic cell adhesion
Authors: Maia Vera , Ortiz-Rivero Sara , Sanz María , Gutierrez-Berzal Javier , Álvarez-Fernández Indira , Gutierrez-Herrero Sara , de Pereda Jose María , Porras Almudena , Guerrero Carmen 
Published: January 2013

Abstract

Background
Previous studies by our group and others have shown that C3G interacts with Bcr-Abl through its SH3-b domain.

Results
In this work we show that C3G and Bcr-Abl form complexes with the focal adhesion (FA) proteins CrkL, p130Cas, Cbl and Abi1 through SH3/SH3-b interactions. The association between C3G and Bcr-Abl decreased upon Abi1 or p130Cas knock-down in K562 cells, which suggests that Abi1 and p130Cas are essential partners in this interaction. On the other hand, C3G, Abi1 or Cbl knock-down impaired adhesion to fibronectin, while p130Cas silencing enhanced it. C3G, Cbl and p130Cas-SH3-b domains interact directly with common proteins involved in the regulation of cell adhesion and migration. Immunoprecipitation and immunofluorescence studies revealed that C3G form complexes with the FA proteins paxillin and FAK and their phosphorylated forms. Additionally, C3G, Abi1, Cbl and p130Cas regulate the expression and phosphorylation of paxillin and FAK. p38α MAPK also participates in the regulation of adhesion in chronic myeloid leukemia cells. It interacts with C3G, CrkL, FAK and paxillin and regulates the expression of paxillin, CrkL and α5 integrin, as well as paxillin phosphorylation. Moreover, double knock-down of C3G/p38α decreased adhesion to fibronectin, similarly to the single silencing of one of these genes, either C3G or p38α. These suggest that C3G and p38α MAPK are acting through a common pathway to regulate cell adhesion in K562 cells, as previously described for the regulation of apoptosis.

Conclusions
Our results indicate that C3G-p38αMAPK pathway regulates K562 cell adhesion through the interaction with FA proteins and Bcr-Abl, modulating the formation of different protein complexes at FA.
Research Resource: The Endometrium Database Resource (EDR)
Authors: Darlington Yolanda , Jeong Jae-Wook , Lee Kevin Y. , Franco Heather L. , Chen Edward S. , McOwiti Apollo , Mistretta Toni-Ann , Steffen David , Becnel Lauren , DeMayo Francesco J. 
Published: January 2013

Abstract
In order to understand the biology of the endometrium and potentially develop new diagnostic tools and treatments for endometrial diseases, the highly orchestrated gene expression/regulation that occurs within the uterus must first be understood. Even though a wealth of information on endometrial gene expression/regulation is available, this information is scattered across several different resources in formats that can be difficult for the average bench scientist to query, integrate, and utilize. The Endometrium Database Resource (EDR) was created as a single evolving resource for protein- and micro-RNA-encoding genes that have been shown by gene expression microarray, Northern blot, or other experiments in the literature to have their expression regulated in the uterus of humans, mice, rats, cows, domestic pigs, guinea pigs, and sheep. Genes are annotated in EDR with basic gene information (eg, gene symbol and chromosome), gene orthologs, and gene ontologies. Links are also provided to external resources for publication/s, nucleic and amino acid sequence, gene product function, and Gene Expression Omnibus (GEO) phase expression graph information. The resource also allows for direct comparison of relative gene expression in different microarray experiments for genes shown in the literature to be differentially expressed in the uterus. It is available via a user-friendly, web-based interface and is available without charge or restriction to the entire scientific community. The EDR can be accessed at http://edr.research.bcm.edu.
On the failure of BD-ℕ and BD, and an application to the anti-specker property
Authors: Lubarsky Robert S. 
Published: January 2013

AbstractWe give the natural topological model for ¬BD-ℕ, and use it to show that the closure of spaces with the anti-Specker property under product does not imply BD-ℕ. Also, the natural topological model for ¬BD is presented. Finally, for some of the realizability models known indirectly to falsify BD-ℕ, it is brought out in detail how BD-ℕ fails.
Keratoconus associated with Corneal Guttata
Authors: Ramos Isaac C , Valbon Bruno F , Pimentel Leonardo N , Caldas Diogo L 
Published: January 2013

ABSTRACT

Purpose
To describe clinical findings of cases with keratoconus and concomitant corneal guttata.

Setting
Rio de Janeiro Corneal Tomography and Biomechanics Study Group, Brazil.

Materials and methods
In a retrospective study including 138 patients with clinical keratoconus, 22 eyes from 11 (8%) patients with keratoconus were identified with the presence of corneal guttata. Complete ophthalmologic examination was performed in all patients, including Scheimpflug rotation tomography (Pentacam HR, Oculus, Wetzlar, Germany), biomechanical study associated with noncontact tonometry [ocular response analyzer (ORA); Reichert, Depew, USA], and specular microscopy (LSM 12000, Bio-Optics, Oregon, USA). The amount of guttata was correlated with biomechanical and tomographic parameters by nonparametric Spearman test.

Results
The mean age was 51.8 ± 20.9 (from 25 to 81) years, nine patients were female (81.9%). The mean of corrected distance visual acuity was 0.20 (20/32) ± 0.49 [from 0 (20/20) to 1.9 (10/800)] LogMar. Eleven eyes had corneal guttae grade I, six eyes grade II, four eyes grade III, and one eye grade IV. The average central keratometric readings were 44.45 ± 2.54 (from 39.70 to 50.60) for flattest K (K1), 46.08 ± 2.69 (from 42.40 to 53.50) for steepest K (K2) and 45.24 ± 2.52 (from 42.00 to 52.20) for average K (Km). Maximal keratometric value (Kmax) averaged 47.63 ± 3.10 (from 43.5 to 55.8) D. The mean CCT was 482.54 ± 52.13 µm (from 398 to 585) and in the thinnest point 474.45 ± 50.32 µm (from 387 to 577). The mean of pachymetric progression indices were 0.83 ± 0.41 (from 0.2 to 2.03) (PPI Min), 1.24 ± 0.53 (from 0.7 to 2.73) (PPI Avg), and 1.79 ± 0.92 (from 0.88 to 4.67) (PPI Max). The mean of ART Min was 710.54 ± 372.47 (from 190.64 to 1985), of ART Avg was 433.18 ± 140.96 (from 141.75 to 678.37), and of ART Max was 315.64 ± 122.69 (from 102.78 to 539.78). The mean of front and back elevation at the thinnest point (using best fit sphere to 8 mm) was 5.35 ± 6.77 (from −4 to 20) and 19.15 ± 16.41 (from 1 to 50) respectively. Belin-Ambrósio deviation index (BAD D) was 3.05 ± 3 (from −0.34 to 11.55). The mean corneal hysteresis (CH) was 8.23 ± 2.05 (from 4.1 to 10.9), corneal resistance factor (CRF) was 7.67 ± 2.4 (from 3.4 to 11.3). The amount of guttata was statistically correlated with Km and K1 (Spearman, p > 0.05).

Conclusion
Keratoconus and cornea guttata can coexist in the same patient. This association can camouflage corneal thinning and protrusion associated with ectasia, but elevation, relational thickness, along with combined tomographic indices and biomechanical properties are altered. The diagnosis should be considered in the complete ophthalmic examination, including corneal topography, and tomographic characterization, along specular documentation of corneal endothelium.

How to cite this article
Ramos IC, Belin MW, Valbon BF, Luz A, Pimentel LN, Caldas DL, Ambrósio R Jr. Keratoconus associated with Corneal Guttata. Int J Kerat Ect Cor Dis 2012;1(3):173-178.
The Impacts of Cation Stoichiometry and Substrate Surface Quality on Nucleation, Structure, Defect Formation, and Intermixing in Complex Oxide Heteroepitaxy–LaCrO3 on SrTiO3(001)
Authors: Qiao L. , Zhang K. H. L. , Bowden M. E. , Varga T. , Shutthanandan V. , Colby R. , Du Y. , Kabius B. , Sushko P. V. , Biegalski M. D. , Chambers S. A. 
Published: January 2013

AbstractThe ability to design and fabricate electronic devices with reproducible properties using complex oxides is critically dependent on our ability to controllably synthesize these materials in thin‐film form. Structure‐property relationships are intimately tied to film and interface composition. Here the effect of cation stoichiometry on structural quality and defect formation in LaCrO3 heteroepitaxial films prepared using molecular beam epitaxy is reported. From first principles the regions of stability of various candidate defects, along with the predicted effects of these defects on structural parameters, are calculated as a function of Cr and O chemical potential. Epitaxial LaCrO3 films readily nucleate and remain coherently strained on SrTiO3(001) over a wide range of La‐to‐Cr atom ratios, but La‐rich films are of considerably lower structural quality than stoichiometric and Cr‐rich films. Cation imbalances are accompanied by anti‐site defect formation. Cation mixing occurs at the interface for all La‐to‐Cr ratios investigated and is not quenched by deposition on SrTiO3(001) at ambient temperature. Indiffused La atoms occupy Sr sites. Intermixing is effectively quenched by using molecular beam epitaxy to deposit LaCrO3 at ambient temperature on defect free Si(001). However, analogous pulsed laser deposition on Si is accompanied by cation mixing.
Photochemical Transformation of Fullerenes
Authors: Wang Jia , Enevold Jenny , Edman Ludvig 
Published: January 2013

AbstractExperimental findings and associated theoretical insights regarding the photochemical transformation of fullerenes are reported, which challenge the conventional wisdom in the field and point out a viable path towards improved fullerene‐based electronic devices. It is shown that the efficiency of the photochemical monomer‐to‐dimer transformation of the fullerene [6,6′]‐phenyl‐C61‐butyric acid methyl ester (PCBM) is strongly dependent on the light intensity, and this is utilized to demonstrate that direct patterning of an electroactive PCBM film can be effectuated by sub‐second UV‐light exposure followed by development in a tuned developer solution. By straightforward analytical reasoning, it is demonstrated that the observed intensity‐dependent monomer‐to‐dimer transformation dictates that a significant back‐reaction to the ground state must be in effect, which presumably originates from the excited‐triplet state. By a combination of numerical modeling and analytical argumentation, it is further shown that the final dimer formation must constitute a bi‐excited reaction between two neighboring monomers photo‐excited to the triplet state.
Possible Chelating Agents for Iron and Aluminium – 4‐Hydroxy‐5‐methyl‐ and 4‐Hydroxy‐1,5‐dimethyl‐3‐pyridinecarboxylic Acid
Authors: Dean Annalisa , Sija Éva , Zsigó Éva , Ferlin Maria Grazia , Marton Daniele , Gandin Valentina , Marzano Cristina , Badocco Denis , Pastore Paolo , Venzo Alfonso , Bertani Roberta , Kiss Tamás , Di Marco Valerio 
Published: January 2013

Abstract4‐Hydroxy‐5‐methyl‐3‐pyridinecarboxylic acid (DQ5) and 4‐hydroxy‐1,5‐dimethyl‐3‐pyridinecarboxylic acid (DQ715) were synthesized and evaluated for possible application in iron and aluminium chelation therapy. Metal ion/ligand solution chemistry, electrochemistry, cytotoxicity and chelation efficiency in vitro were studied. The solution chemistry of each ligand with FeIII or AlIII was investigated in aqueous NaCl solution (0.6 m) at 25 °C by means of potentiometric titrations, UV/Vis spectrophotometry, ESI‐MS and (in the case of AlIII) by 1H NMR measurements. Accordingly, the effects of the 5‐methyl substitution of 4‐hydroxy‐3‐pyridinecarboxylic acid on the stability of Fe and Al complexes were rationalized. Electrochemical measurements allowed to obtain the standard reduction potentials of some FeIII/DQ715 complexes and their kinetic constants. These results indicate that FeIII/DQ715 complexes do not redox cycle in vivo and complex formation is not kinetically limited. The lack of cytotoxicity of DQ715 was demonstrated on human embryonic kidney cells (HEK‐293): the IC50 values calculated from the dose–survival curves were 1.4 (after 24 h treatment) and 0.8 mmol/L (after 48 h treatment). The treatment of cells with DQ715 in the presence of FeIII sensibly reduced antiproliferative activity promoted by the metal ion, which suggests an FeIII chelate effect induced by DQ715. According to our results, DQ715 is a chelator for both metal ions, whereas DQ5 is more suitable as a selective Al chelator.
Influence of the Morphology of Lithiated Copper(I) Sulfides with the Formal Composition “Li2Cu4S3” on Their Stability in Electrochemical Cycling
Authors: Eichhöfer Andreas , Sommer Heino , Andrushko Vasyl , Indris Sylvio , Malik Sharali 
Published: January 2013

AbstractTwo different approaches were developed for the synthesis of lithiated copper(I) sulfide with the formal composition “Li2Cu4S3”. In the first approach, thiolato‐bridged copper cluster complexes [Li(dme)3]2[Cu4(SPh)6] (dme = dimethoxyethane) and [Li(diglyme)2]2[Cu4(SPh)6] (diglyme = diethylene glycol dimethyl ether) were decomposed/thermolized at 400 °C to form the lithiated copper(I) sulfides upon cleavage of the ether ligands and 3 equiv. of SPh2. In the second approach, Li2S and 2 equiv. of Cu2S were allowed to react in quartz ampoules sealed under vacuum at 400 °C. The as‐synthesized powders reveal complex room‐temperature XRD powder patterns with clear differences between the two materials. Scanning electron microscopy reveals that the material synthesized by thermolysis of the cluster material is composed of a porous network of agglomerated nanoparticles, whereas the other material is composed of compact micron‐sized crystals. The initial specific capacities for galvanostatic charging and discharging of nanostructured and porous “Li2Cu4S3” cathodes vs. lithium metal anodes in a limited range between 1.7 and 3 V are ca. 143 A h kg–1. This is 97.3 % of the theoretical value for the exchange of two lithium ions and 5 % higher than for the compact material at ca. 136 A h kg–1. However, we observed that upon prolonged cycling the capacity of the nanostructured and porous “Li2Cu4S3” fades much faster than that of the compact material. This means that after 100 cycles the nanostructured and porous material had faded by 67 %, whereas the compact material still reaches a specific capacity of 109 A h kg–1.