Showing papers by "Yi Chen published in 2008"

EpCAM and α-Fetoprotein Expression Defines Novel Prognostic Subtypes of Hepatocellular Carcinoma

Abstract: The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. Recently, we have identified that a hepatic stem cell marker, epithelial cell adhesion molecule (EpCAM), may serve as an early biomarker of HCC because its expression is highly elevated in premalignant hepatic tissues and in a subset of HCC. In this study, we aimed to identify novel HCC subtypes that resemble certain stages of liver lineages by searching for EpCAM-coexpressed genes. A unique signature of EpCAM-positive HCCs was identified by cDNA microarray analysis of 40 HCC cases and validated by oligonucleotide microarray analysis of 238 independent HCC cases, which was further confirmed by immunohistochemical analysis of an additional 101 HCC cases. EpCAM-positive HCC displayed a distinct molecular signature with features of hepatic progenitor cells including the presence of known stem/progenitor markers such as cytokeratin 19, c-Kit, EpCAM, and activated Wnt-beta-catenin signaling, whereas EpCAM-negative HCC displayed genes with features of mature hepatocytes. Moreover, EpCAM-positive and EpCAM-negative HCC could be further subclassified into four groups with prognostic implication by determining the level of alpha-fetoprotein (AFP). These four subtypes displayed distinct gene expression patterns with features resembling certain stages of hepatic lineages. Taken together, we proposed an easy classification system defined by EpCAM and AFP to reveal HCC subtypes similar to hepatic cell maturation lineages, which may enable prognostic stratification and assessment of HCC patients with adjuvant therapy and provide new insights into the potential cellular origin of HCC and its activated molecular pathways.

Circuit and microarchitecture evaluation of 3D stacking magnetic RAM (MRAM) as a universal memory replacement

Abstract: Magnetic random access memory (MRAM) has been considered as a promising memory technology due to many attractive properties. Integrating MRAM with CMOS logic may incur extra manufacture cost, due to its hybrid magnetic-CMOS fabrication process. Stacking MRAM on top of CMOS logics using 3D integration is a way to minimize this cost overhead. In this paper, we discuss the circuit design issues for MRAM, and present the MRAM cache model. Based on the model, we compare MRAM against SRAM and DRAM in terms of area, performance, and energy. Finally we conduct architectural evaluation for 3D microprocessor stacking with MRAM. The experimental results show that MRAM stacking offers competitive IPC performance with a large reduction in power consumption compared to SRAM and DRAM counterparts.

Template bank for gravitational waveforms from coalescing binary black holes: Nonspinning binaries

Abstract: Gravitational waveforms from the inspiral and ring-down stages of the binary black-hole coalescences can be modeled accurately by approximation/perturbation techniques in general relativity. Recent progress in numerical relativity has enabled us to model also the nonperturbative merger phase of the binary black-hole coalescence problem. This enables us to coherently search for all three stages of the coalescence of nonspinning binary black holes using a single template bank. Taking our motivation from these results, we propose a family of template waveforms which can model the inspiral, merger, and ring-down stages of the coalescence of nonspinning binary black holes that follow quasicircular inspiral. This two-dimensional template family is explicitly parametrized by the physical parameters of the binary. We show that the template family is not only effectual in detecting the signals from black-hole coalescences, but also faithful in estimating the parameters of the binary. We compare the sensitivity of a search (in the context of different ground-based interferometers) using all three stages of the black-hole coalescence with other template-based searches which look for individual stages separately. We find that the proposed search is significantly more sensitive than other template-based searches for a substantial mass range, potentially bringing about remarkable improvement in the event rate of ground-based interferometers. As part of this work, we also prescribe a general procedure to construct interpolated template banks using nonspinning black-hole waveforms produced by numerical relativity.

Increased apoptotic potential and dose‐enhancing effect of gold nanoparticles in combination with single‐dose clinical electron beams on tumor‐bearing mice

Abstract: High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P = 0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P < 0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P < 0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (Cancer Sci 2008; 99: 1479–1484)

Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Abstract: The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy gamma-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to gamma-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed.

Search for gravitational waves from binary inspirals in S3 and S4 LIGO data

Abstract: We report on a search for gravitational waves from the coalescence of compact binaries during the third and fourth LIGO science runs. The search focused on gravitational waves generated during the inspiral phase of the binary evolution. In our analysis, we considered three categories of compact binary systems, ordered by mass: (i) primordial black hole binaries with masses in the range 0.35M_⊙

Adsorptive removal of aromatic organosulfur compounds over the modified Na-Y zeolites

Abstract: The adsorptive removal of organosulfur compounds including dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT) on the various ion-exchanged Na-Y zeolites (with single Cu2+, Zn2+, Ag+ and the combined Cu2+–Zn2+, Zn2+–Nd3+, Ni2+–Nd3+) in the model systems (the n-octane solutions of sulfur compounds and in some cases with small fraction of benzene/toluene) has been systematically compared. The pre-oxidation of the sulfur compounds together with adsorption procedure over Ag-Y and CuZn-Y adsorbents and the solo-oxidation of the sulfur compounds without adsorption were also performed for comparison. It was observed that the desulfurization efficiency follows the order of direct adsorption > oxidation-adsorption > direct-oxidation. The CuZu-Y was found to be a promising competitor to Ag-Y in terms of the desulfurization performance, and the former is more stable than the latter. The influence of various parameters on desulfurization of Ag-Y and CuZn-Y was investigated. The characterization results of the fresh and used samples provide insights into the characteristics of various adsorbents and the sort of interactions between the adsorbed sulfur compounds and the exchanged metal ions. A full regeneration of used Ag-Y can be achieved by air-calcination at 450 °C.

VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy.

Abstract: Background: Anti-vascular endothelial growth factor therapy (VEGF) is an important new treatment modality in oncology. We sought to determine the efficacy and safety of the humanized monoclonal anti-VEGF antibody, bevacizumab, and vinorelbine as treatment for refractory breast cancer and to explore the role of plasma VEGF as a predictor of treatment outcome. Experimental Design: Eligible patients had received one or two prior chemotherapy regimens for metastatic breast cancer or recurred within 12 months of adjuvant therapy and had measurable disease and adequate end-organ function. Patients received bevacizumab 10 mg/kg every 2 weeks, and vinorelbine each week, until tumor progression or prohibitive toxicity. Plasma VEGF was measured at baseline. Results: Among 56 women treated on protocol, bevacizumab and vinorelbine yielded a 34% response rate (95% confidence interval, 22-48%) and median time to progression of 5.5 months. Activity was observed regardless of tumor hormone receptor status or type or extent of prior chemotherapy. Side effects included uncomplicated neutropenia, hypertension, nasal congestion/epistaxis, and neuropathy, consistent with well-described side effects of the respective agents. Three patients had impaired wound healing following surgical procedures. There were only rare instances of thrombosis or clinically significant proteinuria. Lower levels of baseline VEGF were associated with longer time to progression. Conclusions: Bevacizumab and vinorelbine are well tolerated and effective as treatment for refractory breast cancer. Plasma VEGF warrants further evaluation as a prognostic marker for treatment outcome in advanced breast cancer patients receiving anti-VEGF therapy.

GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus.

Abstract: The NCBI Gene Expression Omnibus (GEO) represents the largest public repository of microarray data. However, finding data in GEO can be challenging. We have developed GEOmetadb in an attempt to make querying the GEO metadata both easier and more powerful. All GEO metadata records as well as the relationships between them are parsed and stored in a local MySQL database. A powerful, flexible web search interface with several convenient utilities provides query capabilities not available via NCBI tools. In addition, a Bioconductor package, GEOmetadb that utilizes a SQLite export of the entire GEOmetadb database is also available, rendering the entire GEO database accessible with full power of SQL-based queries from within R. Availability: The web interface and SQLite databases available at http://gbnci.abcc.ncifcrf.gov/geo/. The Bioconductor package is available via the Bioconductor project. The corresponding MATLAB implementation is also available at the same website.

All-sky search for periodic gravitational waves in LIGO S4 data

Abstract: We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50–1000 Hz and with the frequency’s time derivative in the range −1×10^(−8) Hz s^(−1) to zero. Data from the fourth LIGO science run (S4) have been used in this search. Three different semicoherent methods of transforming and summing strain power from short Fourier transforms (SFTs) of the calibrated data have been used. The first, known as StackSlide, averages normalized power from each SFT. A “weighted Hough” scheme is also developed and used, which also allows for a multi-interferometer search. The third method, known as PowerFlux, is a variant of the StackSlide method in which the power is weighted before summing. In both the weighted Hough and PowerFlux methods, the weights are chosen according to the noise and detector antenna-pattern to maximize the signal-to-noise ratio. The respective advantages and disadvantages of these methods are discussed. Observing no evidence of periodic gravitational radiation, we report upper limits; we interpret these as limits on this radiation from isolated rotating neutron stars. The best population-based upper limit with 95% confidence on the gravitational-wave strain amplitude, found for simulated sources distributed isotropically across the sky and with isotropically distributed spin axes, is 4.28×10^(−24) (near 140 Hz). Strict upper limits are also obtained for small patches on the sky for best-case and worst-case inclinations of the spin axes.

Entanglement of macroscopic test masses and the Standard Quantum Limit in laser interferometry

Abstract: We show that the generation of entanglement of two heavily macroscopic mirrors is feasible with state of the art techniques of high-precision laser interferometry. The basis of such a demonstration would be a Michelson interferometer with suspended mirrors and simultaneous homodyne detections at both interferometer output ports. We present the connection between the generation of entanglement and the standard quantum limit (SQL) for a free mass. The SQL is a well-known reference limit in operating interferometers for gravitational-wave detection and provides a measure of when macroscopic entanglement can be observed in the presence of realistic decoherence processes.

Search for gravitational-wave bursts from soft gamma repeaters

Abstract: We present a LIGO search for short-duration gravitational waves (GWs) associated with soft gamma ray repeater (SGR) bursts. This is the first search sensitive to neutron star f modes, usually considered the most efficient GW emitting modes. We find no evidence of GWs associated with any SGR burst in a sample consisting of the 27 Dec. 2004 giant flare from SGR 1806-20 and 190 lesser events from SGR 1806-20 and SGR 1900+14. The unprecedented sensitivity of the detectors allows us to set the most stringent limits on transient GW amplitudes published to date. We find upper limit estimates on the model-dependent isotropic GW emission energies (at a nominal distance of 10 kpc) between 3×1045 and 9×1052 erg depending on waveform type, detector antenna factors and noise characteristics at the time of the burst. These upper limits are within the theoretically predicted range of some SGR models.

Search for gravitational waves associated with 39 gamma-ray bursts using data from the second, third, and fourth LIGO runs

Abstract: We present the results of a search for short-duration gravitational-wave bursts associated with 39 gamma-ray bursts (GRBs) detected by gamma-ray satellite experiments during LIGO’s S2, S3, and S4 science runs. The search involves calculating the crosscorrelation between two interferometer data streams surrounding the GRB trigger time. We search for associated gravitational radiation from single GRBs, and also apply statistical tests to search for a gravitational-wave signature associated with the whole sample. For the sample examined, we find no evidence for the association of gravitational radiation with GRBs, either on a single-GRB basis or on a statistical basis. Simulating gravitational-wave bursts with sine-Gaussian waveforms, we set upper limits on the root-sum-square of the gravitational-wave strain amplitude of such waveforms at the times of the GRB triggers. We also demonstrate how a sample of several GRBs can be used collectively to set constraints on population models. The small number of GRBs and the significant change in sensitivity of the detectors over the three runs, however, limits the usefulness of a population study for the S2, S3, and S4 runs. Finally, we discuss prospects for the search sensitivity for the ongoing S5 run, and beyond for the next generation of detectors.

Physics at BES-III

Abstract: This physics book provides detailed discussions on important topics in $\tau$-charm physics that will be explored during the next few years at \bes3 . Both theoretical and experimental issues are covered, including extensive reviews of recent theoretical developments and experimental techniques. Among the subjects covered are: innovations in Partial Wave Analysis (PWA), theoretical and experimental techniques for Dalitz-plot analyses, analysis tools to extract absolute branching fractions and measurements of decay constants, form factors, and CP-violation and \DzDzb-oscillation parameters. Programs of QCD studies and near-threshold tau-lepton physics measurements are also discussed.

Apoptosis induced by methylene-blue-mediated photodynamic therapy in melanomas and the involvement of mitochondrial dysfunction revealed by proteomics.

Abstract: Methylene blue (MB) is a widely studied agent currently under investigation for its properties relating to photodynamic therapy (PDT). Recent studies have demonstrated that MB exhibits profound phototoxicity affecting a variety of tumor cell lines. However, the mechanistic explanation for methylene-blue-mediated photodynamic therapy (MB-PDT) in the context of melanoma therapy is still obscure. In the present study, B16F1 melanoma cells were treated by MB-PDT under different conditions, and thereafter subjected to cell viability detection assays. MB-PDT could induce intense apoptotic cell death through a series of steps beginning with the photochemical generation of reactive oxygen species that activate the caspase-9/caspase-3 apoptosis pathway. Blocking activation of caspase-3 and induction of oxidative stress by caspase inhibitor and by glutathione, respectively, markedly reduced apoptotic cell death in vitro. Importantly, proteomics study defining altered protein expression in treated cells suggests the involvement of several mitochondrial proteins playing important roles in electron transfer chain, implying mitochondrial dysfunction during the treatment. Furthermore, a transplantable mouse melanoma model was utilized to estimate the effectiveness of MB-PDT in vivo. The treated mice displayed decreased tumor size and prolonged survival days, which was associated with enhanced apoptotic cell death. These results, offering solid evidence of the induction of mitochondria-related apoptosis in tumor cells, reveal new aspects of MB-PDT having potential to be a palliative treatment of melanoma.

Chromosomal Breakpoints in Primary Colon Cancer Cluster at Sites of Structural Variants in the Genome

Abstract: Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors ( n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants ( P < 2.2e−16). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells. [Cancer Res 2008;68(5):1284–95]

High density reconfigurable spin torque non-volatile memory

Abstract: One time programmable memory units include a magnetic tunnel junction cell electrically coupled to a bit line and a word line. The magnetic tunnel junction cell is pre-programmed to a first resistance state, and is configured to switch only from the first resistance state to a second resistance state by passing a voltage across the magnetic tunnel junction cell. In some embodiments, a transistor is electrically coupled between the magnetic tunnel junction cell and the word line or the bit line. In other embodiments, a device having a rectifying switching characteristic, such as a diode or other non-ohmic device, is electrically coupled between the magnetic tunnel junction cell and the word line or the bit line. Methods of pre-programming the one time programmable memory units and reading and writing to the units are also disclosed.

Search for B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) Decays with 2 fb(-1) of p(p)over-bar Collisions

Abstract: We have performed a search for Bs-->mu+mu- and Bd-->mu+mu- decays in ppbar collisions at sqrt(s) = 1.96TeV using 2fb-1 of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron Collider. The observed number of Bs and Bd candidates is consistent with background expectations. The resulting upper limits on the branching fractions are B(Bs-->mu+mu-) mu+mu-) < 1.8X10^-8 at 95% C.L.

Search of S3 LIGO data for gravitational wave signals from spinning black hole and neutron star binary inspirals

Abstract: We report on the methods and results of the first dedicated search for gravitational waves emitted during the inspiral of compact binaries with spinning component bodies We analyze 788 hours of data collected during the third science run (S3) of the LIGO detectors We searched for binary systems using a detection template family specially designed to capture the effects of the spin-induced precession of the orbital plane We present details of the techniques developed to enable this search for spin-modulated gravitational waves, highlighting the differences between this and other recent searches for binaries with nonspinning components The template bank we employed was found to yield high matches with our spin-modulated target waveform for binaries with masses in the asymmetric range 10M⊙

Multilayered core-shell structure of the dispersed phase in high-impact polypropylene

Abstract: The multiphase morphology of high impact polypropylene (hiPP), which is a reactor blend of polypropylene (PP) with ethylene-propylene copolymer, was investigated by transmission electron microscopy, selected area electron diffraction, atomic force microscopy, and field-emission scanning electron microscopy techniques in conjunction with an analysis of the hiPP composition and chain structure based on solvent fractionation, C-13-NMR, and differential scanning calorimetry measurements.

Using RFID technology in produce traceability

Abstract: In recent years, food safety events occur because of epizooty. Many countries build food traceability systems to solve these problems. However, the current food traceability system must be executed by paper work and need a lot of manpower. It also cannot trace and track back the origin and destination of food. Due to the fact that RFID technology can trace object, therefore, it can solve these problems. The research method integrates RFID technologies on the food produce traceability system. Using RFID technology will be easy to trace each object, not only for the goods lots. RFID technology can also record all events automatically and acquire the information about the food production by handhold devices. The research result of this paper is providing an integrated tactility system for the entire food supply chain by RFID technology. The benefit of this research can trace the food production, and let consumers get the complete food production information to choose and buy the safety food.

Double optical spring enhancement for gravitational wave detectors

Abstract: Currently planned second-generation gravitational-wave laser interferometers such as Advanced LIGO exploit the extensively investigated signal-recycling technique. Candidate Advanced LIGO configurations are usually designed to have two resonances within the detection band, around which the sensitivity is enhanced: a stable optical resonance and an unstable optomechanical resonance—which is upshifted from the pendulum frequency due to the so-called optical-spring effect. As an alternative to a feedback control system, we propose an all-optical stabilization scheme, in which a second optical spring is employed, and the test mass is trapped by a stable ponderomotive potential well induced by two carrier light fields whose detunings have opposite signs. The double optical spring also brings additional flexibility in reshaping the noise spectral density and optimizing toward specific gravitational-wave sources. The presented scheme can be extended easily to a multi-optical-spring system that allows further optimization.

A five-year follow-up study of goiter and thyroid nodules in three regions with different iodine intakes in China.

Abstract: Objective: The association between iodine status and the prevalence of goiter and thyroid nodules has been well established but the extent to which different iodine intake levels influence the incidence of goiter and thyroid nodules is unclear. The aim of the study was to determine the incidence of goiter and thyroid nodules in 3 regions with different iodine intake levels: mildly deficient, more than adequate, and excessive. Design, patients and measurements: Of the 3385 un-selected subjects enrolled in 1999 in Panshan, Zhangwu, and Huanghua where median urinary iodine excretion (UIE) was 83.5 μg/l, 242.9 μg/l, and 650.9 μg/l, respectively, 2708 (80.0%) participated in the follow-up study in 2004. The examinations of thyroid ultrasonography, thyroid function, thyroid autoantibodies and UIE were performed at baseline and follow-up. Results: The cumulative incidence of diffuse goiter was 7.1 %, 4.4%, and 6.9%, respectively, higher in Panshan and Huanghua than in Zhangwu (p=0.013 and p=0.015) and that of nodular goiter was 5.0%, 2.4%, and 0.8%, respectively, declining with increasing iodine intake levels (p<0.001). Mild iodine deficiency, chronic iodine excess as well as positive thyroid autoantibodies were associated with the occurrence of goiter [Logistic regression: odds ratio (OR)=1.83 (95% confidence interval (CI) 1.26–2.65), OR=1.46 (95% CI 1.01–2.11 ) and OR=1.68 (95% CI 1.14–2.48), respectively]. The cumulative incidence of single nodule was 4.0%, 5.7%, and 5.6%, respectively and that of multiple nodules was 0.4%, 1.2%, and 1.0%, respectively. Conclusions: The relationship between iodine and the risk for the occurrence of diffuse goiter shows a U-shaped curve. Nodular goiters are more prevalent in iodine-deficient areas.

Spin Torque Random Access Memory Down to 22 nm Technology

Abstract: Spin torque random access memory (ST-MRAM) design spaces down to CMOS 22 nm technology node are explored using a dynamic magnetic tunneling junction (MTJ)-CMOS model. The coupled dynamics of MTJ and CMOS is modeled by a combination of MTJ micromagnetic simulation and CMOS SPICE circuit simulation. The paper analyzes trade-offs between MTJ current threshold, MTJ thermal stability and CMOS driving strength. The analysis provides information on physics requirements and technology bottlenecks for MTJ to achieve maximum capacity supported by CMOS 22 nm technology node. Magnetic solutions for MTJ to fully achieve CMOS 22 nm potential capacities are reviewed.

Salvicine Inactivates β1 Integrin and Inhibits Adhesion of MDA-MB-435 Cells to Fibronectin via Reactive Oxygen Species Signaling

Abstract: Integrin-mediated adhesion to the extracellular matrix plays a fundamental role in tumor metastasis. Salvicine, a novel diterpenoid quinone compound identified as a nonintercalative topoisomerase II poison, possesses a broad range of antitumor and antimetastatic activity. Here, the mechanism underlying the antimetastatic capacity of salvicine was investigated by exploring the effect of salvicine on integrin-mediated cell adhesion. Salvicine inhibited the adhesion of human breast cancer MDA-MB-435 cells to fibronectin and collagen without affecting nonspecific adhesion to poly-l-lysine. The fibronectin-dependent formation of focal adhesions and actin stress fibers was also inhibited by salvicine, leading to a rounded cell morphology. Furthermore, salvicine down-regulated β 1 integrin ligand affinity, clustering and signaling via dephosphorylation of focal adhesion kinase and paxillin. Conversely, salvicine induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. The effect of salvicine on β 1 integrin function and cell adhesion was reversed by U0126 and SB203580, inhibitors of MAPK/ERK kinase 1/2 and p38 MAPK, respectively. Salvicine also induced the production of reactive oxygen species (ROS) that was reversed by ROS scavenger N -acetyl-l-cysteine. N -acetyl-l-cysteine additionally reversed the salvicine-induced activation of ERK and p38 MAPK, thereby maintaining functional β 1 integrin activity and restoring cell adhesion and spreading. Together, this study reveals that salvicine activates ERK and p38 MAPK by triggering the generation of ROS, which in turn inhibits β 1 integrin ligand affinity. These findings contribute to a better understanding of the antimetastatic activity of salvicine and shed new light on the complex roles of ROS and downstream signaling molecules, particularly p38 MAPK, in the regulation of integrin function and cell adhesion. (Mol Cancer Res 2008;6(2):194–204)

Synthesis and characterization of smooth ultrananocrystalline diamond films via low pressure bias-enhanced nucleation and growth

Abstract: This letter describes the fundamental process underlying the synthesis of ultrananocrystalline diamond (UNCD) films, using a new low-pressure, heat-assisted bias-enhanced nucleation (BEN)/bias enhanced growth (BEG) technique, involving H2∕CH4 gas chemistry. This growth process yields UNCD films similar to those produced by the Ar-rich/CH4 chemistries, with pure diamond nanograins (3–5nm), but smoother surfaces (∼6nm rms) and higher growth rate (∼1μm∕h). Synchrotron-based x-Ray absorption spectroscopy, atomic force microscopy, and transmission electron microscopy studies on the BEN-BEG UNCD films provided information critical to understanding the nucleation and growth mechanisms, and growth condition-nanostructure-property relationships.

Memory array with read reference voltage cells

Abstract: The present disclosure relates to memory arrays with read reference voltage cells. In particular the present disclosure relates to variable resistive memory cell apparatus and arrays that include a high resistance state reference memory cell and a low resistance state reference memory cell that provides a reliable average reference voltage on chip to compare to a read voltage of a selected memory cell and determine if the selected memory cell is in the high resistance state or low resistance state. These memory arrays are particularly suitable for use with spin-transfer torque memory cells and resolves many systematic issues related to generation of a reliable reference voltage.

Astrophysically triggered searches for gravitational waves: status and prospects

Abstract: In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from γ-ray and x-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational-wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information are also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target.