bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multitechnique evaluation of topical corticosteroid treatment
Authors: Josse G. , Rouvrais C. , Mas A. , Haftek M. , Delalleau A. , Ferraq Y. , Ossant F. , George J. , Lagarde J. M. , Schmitt A. M. 
Published: August 2008

Background/purpose: Cortiscosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long‐term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during cortiscosteroids treatment. The potential of skin mechanical measurement and ultrasound radio frequency (RF) signal analysis are proposed as new measures more closely related to the functional impairments.Methods: Thirteen young healthy women volunteers had two applications per day on one arm of topical Clobetasol propionate 0.05% for 28 days, and they were followed for 28 days more. Skin modifications were studied by high‐frequency ultrasound imaging, ultrasound RF signal analysis, optical coherence tomography and by the suction test.Results: For all the techniques, a statistically significant change is observed with treatment. Large variations, around 30%, are observed for all techniques, but less for ultrasound imaging (10%). Dermis and epidermis thickness presented stable measurements on the nontreated zone. At the end of the study, measures returned to normal. The dynamic is mainly observed within the first 14 days of treatment and within the first 14 days after its cessation.Conclusion: Similar dynamics of skin modification during cortiscosteroid treatment was observed with very different techniques. Moreover, the potential of RF ultrasound analysis and mechanical skin measurement for characterizing skin structural and functional impairments has been evaluated.
Assessment of moisturizers and barrier function restoration using dynamic methods
Authors: Rosado Catarina , Pinto Pedro , Rodrigues Luis Monteiro 
Published: August 2008

Background/purpose: Dynamic methods, such as the mathematical modelling of the transepidermal water loss curves that result from a plastic occlusion stress test (POST), enable the complete characterization of the dynamic water balance established between the deep and the superficial skin structures. Previous studies have indicated that this methodology was able to detect impaired barrier function and differentiate normal and dry skin. The objective of the present study is to apply the discriminative capacity of the model to the efficacy testing of moisturizing products.Methods: A moisturizing cream containing urea was applied for 2 weeks to the lower leg of volunteers with dry skin. After this period, a POST was performed in the treated and control untreated site and a mathematical model was adjusted to the resulting desorption curves.Results: Results indicate that, after treatment of the skin with the cream for 2 weeks, statistically different kinetic parameters are obtained in the treated site, which suggests an improvement in the water dynamic balance and skin barrier. The data generated by this study was compared with that obtained in a similar investigation that was performed a year earlier. Analysis of the dispersion of results indicates that the method has good reproducibility.Conclusions: These findings confirm that the method has enough sensitivity to assess in vivo the effect of moisturizers on human skin, and also that this evaluation can be performed in a shorter period than that required by the regression method. This methodology can also be considered more informative, because the analysis of the different parameters obtained by the model is indicative of the mechanism of action of the product applied to the skin.
Underfill Filler
Settling Effect on the Die Backside Interfacial Stresses of Flip Chip
Packages
Authors: Chen Cheng-fu , Karulkar Pramod
C. 
Published: August 2008

Abstract
Underfill is usually modeled as an isotropic medium containing uniformly distributed filler particles. However, filler particles tend to settle (or segregate) and thus alter the mechanical response of the flip chip die attachment package. The integrity of such flip chip attachment is different from that with an ideal, isotropic underfill with very uniform distribution of filler. We analyzed the thermomechanical implications of filler settling to the stresses along the die/underfill interface by considering different profiles for the local concentration of filler and calculating their effective material properties by employing the Mori–Tanaka method. As the worst-case scenario, direct silicon die attach with solder bumps was assumed to analyze the interfacial stresses, which were predicted in trend by a simplified multilayered stack model and calculated in detail by finite element simulation. The filler settling has a localized but strong influence on the interfacial peeling stress near the edge of the die. The extent of this influence is determined by the profile of filler settling: (1) if the filler is assumed to settle in the form of a bilayer, then the peeling stress near the die’s edge increases and it is directly proportional to the average volume fraction of the filler; (2) if the filler is assumed to settle gradually, then the magnitude of the peeling stress near the edge of the die becomes smaller as the local filler volume fraction near the die interface increases. The filler settling has no significant effect on the other components of the interfacial stresses. The edge fillet of underfill in pure resin can locally reverse the direction of the interfacial peeling stress and increase the interfacial shearing stress near the die’s edge.
A Convection/Radiation
Temperature Control System for High Power Density Electronic Device
Testing
Authors: Sweetland Matthew , Lienhard John
    H. , Slocum Alexander
H. 
Published: August 2008

Abstract
Active control of die-level temperature is required during production testing of high power microprocessors in order to ensure accurate performance classification, but control is becoming more difficult as the device power densities increase. With power densities approaching 100 W/cm2, the current passive control systems are no longer able to maintain the required temperature tolerance for production testing. This paper describes the design and testing of a temperature control system that combines high performance impingement cooling with higher power laser heating with application to packaged integrated circuit devices under dynamic testing conditions. Also presented are system design concepts and experimental results for typical microprocessor thermal test vehicles.
Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration
Authors: Yi K , Mujat M , Park B H , Sun W , Miller J W , Seddon J M , Young L H , de Boer J F , Chen T C 
Published: August 2008

Background/aims:To demonstrate how spectral domain optical coherence tomography (SDOCT) can better evaluate drusen and associated anatomical changes in eyes with non-neovascular age-related macular degeneration (AMD) compared with time domain optical coherence tomography (TDOCT).Methods:Images were obtained from three eyes of three patients with AMD using an experimental SDOCT system. Both a titanium–sapphire (Ti:sapphire) laser and a superluminescent diode (SLD) were used as a broadband light source to achieve cross-sectional images of the retina. A qualitative and quantitative analysis was performed for structural changes associated with non-neovascular AMD. An automated algorithm was developed to analyse drusen area and volume from SDOCT images. TDOCT was performed using the fast macular scan (StratusOCT, Carl Zeiss Meditec, Dublin, California).Results:SDOCT images can demonstrate structural changes associated with non-neovascular AMD. A new SDOCT algorithm can determine drusen area, drusen volume and proportion of drusen.Conclusions:With new algorithms to determine drusen area and volume and its unprecedented simultaneous ultra-high speed ultra-high resolution imaging, SDOCT can improve the evaluation of structural abnormalities in non-neovascular AMD.
AMP-Activated Protein Kinase Signaling Results in Cytoplasmic Sequestration of p27
Authors: Short John D. , Houston Kevin D. , Dere Ruhee , Cai Sheng-Li , Kim Jinhee , Johnson Charles L. , Broaddus Russell R. , Shen Jianjun , Miyamoto Susie , Tamanoi Fuyuhiko , Kwiatkowski David , Mills Gordon B. , Walker Cheryl Lyn 
Published: August 2008

AbstractTuberin, the Tsc2 gene product, integrates the phosphatidylinositol 3-kinase/mitogen-activated protein kinase (mitogenic) and LKB1/AMP-activated protein kinase (AMPK; energy) signaling pathways, and previous independent studies have shown that loss of tuberin is associated with elevated AMPK signaling and altered p27 function. In Tsc2-null tumors and tumor-derived cells from Eker rats, we observed elevated AMPK signaling and concordant cytoplasmic mislocalization of p27. Cytoplasmic localization of p27 in Tsc2-null cells was reversible pharmacologically using inhibitors of the LKB1/AMPK pathway, and localization of p27 to the cytoplasm could be induced directly by activating AMPK physiologically (glucose deprivation) or genetically (constitutively active AMPK) in Tsc2-proficient cells. Furthermore, AMPK phosphorylated p27 in vitro on at least three sites including T170 near the nuclear localization signal, and T170 was shown to determine p27 localization in response to AMPK signaling. p27 functions in the nucleus to suppress cyclin-dependent kinase-2 (Cdk2) activity and has been reported to mediate an antiapoptotic function when localized to the cytoplasm. We found that cells with elevated AMPK signaling and cytoplasmic p27 localization exhibited elevated Cdk2 activity, which could be suppressed by inhibiting AMPK signaling. In addition, cells with elevated AMPK signaling and cytoplasmic p27 localization were resistant to apoptosis, which could be overcome by inhibition of AMPK signaling and relocalization of p27 to the nucleus. These data show that AMPK signaling determines the subcellular localization of p27, and identifies loss of integration of pathways controlling energy balance, the cell cycle, and apoptosis due to aberrant AMPK and p27 function as a feature of cells that have lost the Tsc2 tumor suppressor gene. [Cancer Res 2008;68(16):6496–506]
Octamer 4 Small Interfering RNA Results in Cancer Stem Cell–Like Cell Apoptosis
Authors: Hu Tingsong , Liu Shanrong , Breiter Deborah R. , Wang Fang , Tang Ying , Sun Shuhan 
Published: August 2008

Abstract
Octamer 4 (Oct4), a member of the POU family of transcription factors, plays a key role in the maintenance of pluripotency and proliferation potential of embryonic stem cells. Cancer stem cell–like cells (CSCLC) are reported to be a minor population in tumors or even in tumor cell lines which also express Oct4. The role of Oct4 in CSCLCs still remains to be defined. In our study, we show that, in vitro, almost all murine Lewis lung carcinoma 3LL cells and human breast cancer MCF7 cells express Oct4 at high levels. This expression of Oct4 is successfully reduced by small interfering RNA, which eventually results in cell apoptosis. The signal pathway Oct4/Tcl1/Akt1 has been observed to be involved in this event. The repression of Oct4 reduces Tcl1 expression and further down-regulates the level of p-Ser.473-Akt1. In vivo, only ∼5% of tumor cells were detected to express Oct4 in established 3LL and MCF7 tumor models, respectively. Small interfering RNA against Oct4 successfully decreases the CSCLCs and markedly inhibits tumor growth. In summary, we show that Oct4 might maintain the survival of CSCLCs partly through Oct4/Tcl1/Akt1 by inhibiting apoptosis, which strongly indicates that targeting Oct4 may have important clinical applications in cancer therapy. [Cancer Res 2008;68(16):6533–40]
Inhibition of the Sodium/Potassium ATPase Impairs N-Glycan Expression and Function
Authors: Zavareh Reza Beheshti , Lau Ken S. , Hurren Rose , Datti Alessandro , Ashline David J. , Gronda Marcela , Cheung Pam , Simpson Craig D. , Liu Wei , Wasylishen Amanda R. , Boutros Paul C. , Shi Hui , Vengopal Amudha , Jurisica Igor , Penn Linda Z. , Reinhold Vern N. , Ezzat Shereen , Wrana Jeff , Rose David R. , Schachter Harry , Dennis James W. , Schimmer Aaron D. 
Published: August 2008

Abstract
Aberrant N-linked glycans promote the malignant potential of cells by enhancing the epithelial-to-mesenchymal transition and the invasive phenotype. To identify small molecule inhibitors of N-glycan biosynthesis, we developed a chemical screen based on the ability of the tetravalent plant lectin L-phytohemagglutinin (L-PHA) to bind and crosslink surface glycoproteins with β1,6GlcNAc-branched complex type N-glycans and thereby induce agglutination and cell death. In this screen, Jurkat cells were treated with a library of off-patent chemicals (n = 1,280) to identify molecules that blocked L-PHA–induced death. The most potent hit from this screen was the cardiac glycoside (CG) dihydroouabain. In secondary assays, a panel of CGs was tested for their effects on L-PHA–induced agglutination and cell death. All of the CGs tested inhibited L-PHA–induced death in Jurkat cells, and the most potent CG tested was digoxin with an EC50 of 60 ± 20 nmol/L. Digoxin also increased the fraction of some concanavalin A–binding N-glycans. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, digoxin specifically increased GlcNAc1Man3GlcNAc2Fuc1 and GlcNAc2Man3GlcNAc2Fuc1 oligosaccharides demonstrating an impairment of the N-glycan pathway. Consistent with this effect on the N-glycan pathway, digoxin inhibited N-glycosylation–mediated processes of tumor cell migration and invasion. Furthermore, digoxin prevented distant tumor formation in two mouse models of metastatic prostate cancer. Thus, taken together, our high throughput screen identified CGs as modifiers of the N-glycan pathway. These molecules can be used as tools to better understand the role of N-glycans in normal and malignant cells. Moreover, these results may partly explain the anticancer effect of CGs in cardiovascular patients. [Cancer Res 2008;68(16):6688–96]
Tumors Sound the Alarmin(s)
Authors: Coffelt Seth B. , Scandurro Aline B. 
Published: August 2008

Abstract
Recent evidence suggests that inflammatory molecules play critical roles in the development and progression of numerous tumors. However, one specific group of inflammatory molecules whose importance has been established in host immune responses, termed alarmins, has been largely overlooked in cancer biology. The function of several alarmins—including the defensins, LL-37, and HMGB1—in tumor development, progression, or suppression is discussed here. Taken together, these studies indicate that alarmins represent potential new targets for manipulation in a variety of tumors. [Cancer Res 2008;68(16):6482–5]
Variants in the ATM Gene Associated with a Reduced Risk of Contralateral Breast Cancer
Authors: Concannon Patrick , Haile Robert W. , Børresen-Dale Anne-Lise , Rosenstein Barry S. , Gatti Richard A. , Teraoka Sharon N. , Diep Anh T. , Jansen Laila , Atencio David P. , Langholz Bryan , Capanu Marinela , Liang Xiaolin , Begg Colin B. , Thomas Duncan C. , Bernstein Leslie , Olsen Jørgen H. , Malone Kathleen E. , Lynch Charles F. , Anton-Culver Hoda , Bernstein Jonine L. ,   for the Women's Environment, Cancer, and Radiation Epidemiology Study Collaborative Group
Published: August 2008

Abstract
Between 5% and 10% of women who survive a first primary breast cancer will subsequently develop a second primary cancer in the contralateral breast. The Women's Environment, Cancer, and Radiation Epidemiology Study was designed to identify genetic and environmental determinants of contralateral breast cancer (CBC). In this study, 708 women with asynchronous CBC served as cases and 1,397 women with unilateral breast cancer served as controls. ATM, a serine-threonine kinase, controls the cellular response to DNA double-strand breaks, and has been implicated in breast cancer risk. Complete mutation screening of the ATM gene in all 2,105 study participants identified 240 distinct sequence variants; only 15 were observed in &gt;1% of subjects. Among the rare variants, deleterious alleles resulting in loss of ATM function were associated with a nonsignificant increase in risk of CBC. In contrast, carriers of common variants had a statistically significant reduction in risk of CBC. Four of these 15 variants were individually associated with a significantly decreased risk of second primary breast cancer [c.1899-55T&gt;G, rate ratio (RR), 0.5; 95% confidence interval (CI), 0.3–0.8; c.3161C&gt;G, RR, 0.5; 95% CI, 0.3–0.9; c.5558A&gt;T, RR, 0.2; 95% CI, 0.1–0.6; c.6348-54T&gt;C RR, 0.2; 95% CI, 0.1–0.8]. These data suggest that some alleles of ATM may exert an antineoplastic effect, perhaps by altering the activity of ATM as an initiator of DNA damage responses or a regulator of p53. [Cancer Res 2008;68(16):6486–91]
Peptide Aptamers Targeting Mutant p53 Induce Apoptosis in Tumor Cells
Authors: Guida Elisa , Bisso Andrea , Fenollar-Ferrer Cristina , Napoli Marco , Anselmi Claudio , Girardini Javier E. , Carloni Paolo , Del Sal Giannino 
Published: August 2008

Abstract
Mutations in the p53 tumor suppressor gene frequently result in expression of p53 point mutants that accumulate in cancer cells and actively collaborate with tumor progression through the acquisition of novel properties. Interfering with mutant p53 functions may represent a valid alternative for blocking tumor growth and development of aggressive phenotypes. The interactions and activities of selected proteins can be specifically modulated by the binding of peptide aptamers (PA). In the present work, we isolated PAs able to interact more efficiently with p53 conformational mutants compared with wild-type p53. The interaction between mutant p53 and PAs was further characterized using molecular modeling. Transient expression of PAs was able to reduce the transactivation activity of mutant p53 and to induce apoptosis specifically in cells expressing mutant p53. These PAs could provide a potential strategy to inhibit the oncogenic functions of mutant p53 and improve mutant p53-targeted cancer therapies. [Cancer Res 2008;68(16):6550–8]
Role of hMOF-Dependent Histone H4 Lysine 16 Acetylation in the Maintenance of TMS1/ASC Gene Activity
Authors: Kapoor-Vazirani Priya , Kagey Jacob D. , Powell Doris R. , Vertino Paula M. 
Published: August 2008

Abstract
Epigenetic silencing of tumor suppressor genes in human cancers is associated with aberrant methylation of promoter region CpG islands and local alterations in histone modifications. However, the mechanisms that drive these events remain unclear. Here, we establish an important role for histone H4 lysine 16 acetylation (H4K16Ac) and the histone acetyltransferase hMOF in the regulation of TMS1/ASC, a proapoptotic gene that undergoes epigenetic silencing in human cancers. In the unmethylated and active state, the TMS1 CpG island is spanned by positioned nucleosomes and marked by histone H3K4 methylation. H4K16Ac was uniquely localized to two sharp peaks that flanked the unmethylated CpG island and corresponded to strongly positioned nucleosomes. Aberrant methylation and silencing of TMS1 was accompanied by loss of the H4K16Ac peaks, loss of nucleosome positioning, hypomethylation of H3K4, and hypermethylation of H3K9. In addition, a single peak of histone H4 lysine 20 trimethylation was observed near the transcription start site. Down-regulation of hMOF or another component of the MSL complex resulted in a gene-specific decrease in H4K16Ac, loss of nucleosome positioning, and silencing of TMS1. Gene silencing induced by H4K16 deacetylation occurred independently of changes in histone methylation and DNA methylation and was reversed on hMOF reexpression. These results indicate that the selective marking of nucleosomes flanking the CpG island by hMOF is required to maintain TMS1 gene activity and suggest that the loss of H4K16Ac, mobilization of nucleosomes, and transcriptional down-regulation may be important events in the epigenetic silencing of certain tumor suppressor genes in cancer. [Cancer Res 2008;68(16):6810–21]
Cross-talk between LPA1 and Epidermal Growth Factor Receptors Mediates Up-regulation of Sphingosine Kinase 1 to Promote Gastric Cancer Cell Motility and Invasion
Authors: Shida Dai , Fang Xianjun , Kordula Tomasz , Takabe Kazuaki , Lépine Sandrine , Alvarez Sergio E. , Milstien Sheldon , Spiegel Sarah 
Published: August 2008

Abstract
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRNA and protein in gastric cancer MKN1 cells but had no effect on SphK2. LPA also up-regulated SphK1 expression in other human cancer cells that endogenously express the LPA1 receptor, such as DLD1 colon cancer cells and MDA-MB-231 breast cancer cells, but not in HT29 colon cancer cells or MDA-MB-453 breast cancer cells, which do not express the LPA1 receptor. An LPA1 receptor antagonist or down-regulation of its expression prevented SphK1 and S1P3 receptor up-regulation by LPA. LPA transactivated the epidermal growth factor receptor (EGFR) in these cells, and the EGFR inhibitor AG1478 attenuated the increased SphK1 and S1P3 expression induced by LPA. Moreover, down-regulation of SphK1 attenuated LPA-stimulated migration and invasion of MNK1 cells yet had no effect on expression of neovascularizing factors, such as interleukin (IL)-8, IL-6, urokinase-type plasminogen activator (uPA), or uPA receptor induced by LPA. Finally, down-regulation of S1P3, but not S1P1, also reduced LPA-stimulated migration and invasion of MKN1 cells. Collectively, our results suggest that SphK1 is a convergence point of multiple cell surface receptors for three different ligands, LPA, EGF, and S1P, which have all been implicated in regulation of motility and invasiveness of cancer cells. [Cancer Res 2008;68(16):6569–77]
Modulation of Protective T Cell Immunity by Complement Inhibitor Expression on Tumor Cells
Authors: Varela Juan C. , Imai Masaki , Atkinson Carl , Ohta Rieko , Rapisardo Michelle , Tomlinson Stephen 
Published: August 2008

Abstract
Complement-inhibitory proteins expressed on cancer cells can provide protection from antitumor antibodies and may potentially modulate the induction of an immune response to tumor-associated antigens. In the current study, we investigated the consequences of complement inhibitor down-regulation on the effector and inductive phases of an immune response. Stable small interfering RNA–mediated down-regulation of the complement inhibitor Crry on MB49 murine bladder cancer cells increased their susceptibility to monoclonal antibody and complement in vitro. In a syngeneic model of metastatic cancer, the down-regulation of Crry on i.v.-injected MB49 cells was associated with a significant decrease in tumor burden and an increase in the survival of challenged mice. However, monoclonal antibody therapy had no additional benefit. There was an antitumor IgG response, but the response was not effected by Crry down-regulation on inoculated tumor cells. Down-regulation of Crry on MB49 cells resulted in an enhanced antitumor T-cell response in challenged mice (measured by lymphocyte IFN-γ secretion), and CD8+ T cell depletion of mice prior to injection of MB49 cells completely abrogated the effect of Crry down-regulation on tumor burden and survival. Deficiency of C3 also abrogated the effect of Crry down-regulation on the survival of MB49-challenged mice, indicating a complement-dependent mechanism. These data indicate that complement inhibitors expressed on a tumor cell can suppress a T cell response and that enhancing complement activation on a tumor cell surface can promote protective T cell immunity. [Cancer Res 2008;68(16):6734–42]