Showing papers by "Tongji University published in 2012"

Identifying ChIP-seq enrichment using MACS

Abstract: Model-based analysis of ChIP-seq (MACS) is a computational algorithm that identifies genome-wide locations of transcription/chromatin factor binding or histone modification from ChIP-seq data. MACS consists of four steps: removing redundant reads, adjusting read position, calculating peak enrichment and estimating the empirical false discovery rate (FDR). In this protocol, we provide a detailed demonstration of how to install MACS and how to use it to analyze three common types of ChIP-seq data sets with different characteristics: the sequence-specific transcription factor FoxA1, the histone modification mark H3K4me3 with sharp enrichment and the H3K36me3 mark with broad enrichment. We also explain how to interpret and visualize the results of MACS analyses. The algorithm requires ∼3 GB of RAM and 1.5 h of computing time to analyze a ChIP-seq data set containing 30 million reads, an estimate that increases with sequence coverage. MACS is open source and is available from http://liulab.dfci.harvard.edu/MACS/ .

Band Engineering of Thermoelectric Materials

Abstract: Lead chalcogenides have long been used for space-based and thermoelectric remote power generation applications, but recent discoveries have revealed a much greater potential for these materials. This renaissance of interest combined with the need for increased energy efficiency has led to active consideration of thermoelectrics for practical waste heat recovery systems—such as the conversion of car exhaust heat into electricity. The simple high symmetry NaCl-type cubic structure, leads to several properties desirable for thermoelectricity, such as high valley degeneracy for high electrical conductivity and phonon anharmonicity for low thermal conductivity. The rich capabilities for both band structure and microstructure engineering enable a variety of approaches for achieving high thermoelectric performance in lead chalcogenides. This Review focuses on manipulation of the electronic and atomic structural features which makes up the thermoelectric quality factor. While these strategies are well demonstrated in lead chalcogenides, the principles used are equally applicable to most good thermoelectric materials that could enable improvement of thermoelectric devices from niche applications into the mainstream of energy technologies.

Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial

Abstract: Summary Background Afatinib, an irreversible ErbB-family blocker, has shown preclinical activity when tested in EGFR mutant models with mutations that confer resistance to EGFR tyrosine-kinase inhibitors. We aimed to assess its efficacy in patients with advanced lung adenocarcinoma with previous treatment failure on EGFR tyrosine-kinase inhibitors. Methods In this phase 2b/3 trial, we enrolled patients with stage IIIB or IV adenocarcinoma and an Eastern Cooperative Oncology Group performance (ECOG) performance score of 0–2 who had received one or two previous chemotherapy regimens and had disease progression after at least 12 weeks of treatment with erlotinib or gefitinib. We used a computer-generated sequence to randomly allocate patients (2:1) to either afatinib (50 mg per day) or placebo; all patients received best supportive care. Randomisation was done in blocks of three and was stratified by sex and baseline ECOG performance status (0–1 vs 2). Investigators, patients, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival (from date of randomisation to death), analysed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00656136. Findings Between May 26, 2008, and Sept 21, 2009, we identified 697 patients, 585 of whom were randomly allocated to treatment (390 to afatinib, 195 to placebo). Median overall survival was 10·8 months (95% CI 10·0–12·0) in the afatinib group and 12·0 months (10·2–14·3) in the placebo group (hazard ratio 1·08, 95% CI 0·86–1·35; p=0·74). Median progression-free survival was longer in the afatinib group (3·3 months, 95% CI 2·79–4·40) than it was in the placebo group (1·1 months, 0·95–1·68; hazard ratio 0·38, 95% CI 0·31–0·48; p Interpretation Although we recorded no benefit in terms of overall survival with afatinib (which might have been affected by cancer treatments given after progression in both groups), our findings for progression-free survival and response to treatment suggest that afatinib could be of some benefit to patients with advanced lung adenocarcinoma who have failed at least 12 weeks of previous EGFR tyrosine-kinase inhibitor treatment. Funding Boehringer Ingelheim Inc.

Structure-based prediction of protein–protein interactions on a genome-wide scale

Abstract: Protein–protein interactions, essential for understanding how a cell functions, are predicted using a new method that combines protein structure with other computationally and experimentally derived clues The analysis of protein-interaction networks is essential to an understanding of the regulatory processes in a living cell Many methods have been developed with a view to predicting protein–protein interactions (PPIs) at a genome-wide level, although the differences obtained using these approaches suggest that there are still factors unaccounted for Barry Honig and colleagues have developed a new way of predicting PPIs that is based on the proteins' three-dimensional structures and functional data Tests of several predictions of the new algorithm, known as PREPPI, confirm the accuracy of the results The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms1,2 Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification3, as well as from manual curation of experiments on individual systems4 A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein–protein interactions (PPIs)5,6 Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages7,8,9 Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins

Enhanced Adsorptive Removal of Methyl Orange and Methylene Blue from Aqueous Solution by Alkali-Activated Multiwalled Carbon Nanotubes

Abstract: An alkali-acitvated method was explored to synthesize activated carbon nanotubes (CNTs-A) with a high specific surface area (SSA), and a large number of mesopores. The resulting CNTs-A were used as an adsorbent material for removal of anionic and cationic dyes in aqueous solutions. Experimental results indicated that CNTs-A have excellent adsorption capacity for methyl orange (149 mg/g) and methylene blue (399 mg/g). Alkali-activation treatment of CNTs increased the SSA and pore volume (PV), and introduced oxygen-containing functional groups on the surface of CNTs-A, which would be beneficial to improving the adsorption affinity of CNTs-A for removal of dyes. Kinetic regression results shown that the adsorption kinetic was more accurately represented by a pseudo second-order model. The overall adsorption process was jointly controlled by external mass transfer and intra-particle diffusion, and intra-particle diffusion played a dominant role. Freundlich isotherm model showed a better fit with adsorption da...

Carbon-Dot-Based Dual-Emission Nanohybrid Produces a Ratiometric Fluorescent Sensor for In Vivo Imaging of Cellular Copper Ions

Abstract: A sensitive biosensor: A strategy for the intracellular imaging of Cu(2+) ions has been developed by integrating a recognition molecule, N-(2-aminoethyl)-N,N,N'tris(pyridin-2-ylmethyl)ethane-1,2-diamine (AE-TPEA), into a hybrid system composed of carbon and CdSe/ZnS quantum dots.

Robust and efficient subspace segmentation via least squares regression

Abstract: This paper studies the subspace segmentation problem which aims to segment data drawn from a union of multiple linear subspaces. Recent works by using sparse representation, low rank representation and their extensions attract much attention. If the subspaces from which the data drawn are independent or orthogonal, they are able to obtain a block diagonal affinity matrix, which usually leads to a correct segmentation. The main differences among them are their objective functions. We theoretically show that if the objective function satisfies some conditions, and the data are sufficiently drawn from independent subspaces, the obtained affinity matrix is always block diagonal. Furthermore, the data sampling can be insufficient if the subspaces are orthogonal. Some existing methods are all special cases. Then we present the Least Squares Regression (LSR) method for subspace segmentation. It takes advantage of data correlation, which is common in real data. LSR encourages a grouping effect which tends to group highly correlated data together. Experimental results on the Hopkins 155 database and Extended Yale Database B show that our method significantly outperforms state-of-the-art methods. Beyond segmentation accuracy, all experiments demonstrate that LSR is much more efficient.

Carbon dot-based inorganic-organic nanosystem for two-photon imaging and biosensing of pH variation in living cells and tissues.

Abstract: A carbon dot (C-Dot)-based two-photon fluorescent probe has been developed for the monitoring of pH changes across a broad range with high sensitivity and selectivity. The inorganic-organic probe also shows good biocompatibility and cell permeability, and thus can be successfully applied in bioimaging and biosensing of physiological pH in living cells, as well as living tissues at a depth of 65-185 μm.

State of the art of carbon nanotube fibers: opportunities and challenges.

Abstract: The superb mechanical and physical properties of individual carbon nanotubes (CNTs) have provided the impetus for researchers in developing high-performance continuous fibers based upon CNTs. The reported high specific strength, specific stiffness and electrical conductivity of CNT fibers demonstrate the potential of their wide application in many fields. In this review paper, we assess the state of the art advances in CNT-based continuous fibers in terms of their fabrication methods, characterization and modeling of mechanical and physical properties, and applications. The opportunities and challenges in CNT fiber research are also discussed.

Facile Ultrasonic Synthesis of CoO Quantum Dot/Graphene Nanosheet Composites with High Lithium Storage Capacity

Abstract: In this paper, we report a facile ultrasonic method to synthesize well-dispersed CoO quantum dots (3-8 nm) on graphene nanosheets at room temperature by employing Co(4)(CO)(12) as cobalt precursor. The prepared CoO/graphene composites displayed high performance as an anode material for lithium-ion battery, such as high reversible lithium storage capacity (1592 mAh g(-1) after 50 cycles), high Coulombic efficiency (over 95%), excellent cycling stability, and high rate capability (1008 mAh g(-1) with a total retention of 77.6% after 50 cycles at a current density of 1000 mA g(-1), dramatically increased from the initial 50 mA g(-1)). The extraordinary performance arises from the structure advantages of the composites: the nanosized CoO quantum dots with high dispersity on conductive graphene substrates supply not only large quantity of accessible active sites for lithium-ion insertion but also good conductivity and short diffusion length for lithium ions, which are beneficial for high capacity and rate capability. Meanwhile, the isolated CoO quantum dots anchored tightly on the graphene nanosheets can effectively circumvent the volume expansion/contraction associated with lithium insertion/extraction during discharge/charge processes, which is good for high capacity as well as cycling stability. Moreover, regarding the anomalous behavior of capacity increase with cycles (activation effect) observed, we proposed a tentative hypothesis stressing the competition between the conductivity increase and the amorphorization of the composite electrodes during cycling in determining the trends of the capacity, in the hope to gain a fuller understanding of the inner working of the novel nanostructured electrode-based lithium-ion batteries.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver - Update 2012

Abstract: Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative

Abstract: Background: This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women participating in the Women’s Health Initiative (WHI). Methods: The WHI recruited 161 808 postmenopausal women aged 50 to 79 years at 40 clinical centers across the United States from 1993 to 1998 with ongoingfollow-up.Thecurrentanalysisincludesdatathrough 2005. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. Cox proportional hazards models were used to estimate the risk of DM by statin use, with adjustmentsforpropensityscoreandotherpotentialconfounding factors. Subgroup analyses by race/ethnicity, obesity status, and age group were conducted to uncover effect modification. Results: This investigation included 153840 women without DM and no missing data at baseline. At baseline,7.04%reportedtakingstatinmedication.Therewere 10242incidentcasesofself-reportedDMover1004466 person-years of follow-up. Statin use at baseline was associatedwithanincreasedriskofDM(hazardratio[HR], 1.71; 95% CI, 1.61-1.83). This association remained afteradjustingforotherpotentialconfounders(multivariateadjusted HR,1.48; 95% CI, 1.38-1.59) and was observedforalltypesofstatinmedications.Subsetanalyses evaluating the association of self-reported DM with longitudinal measures of statin use in 125575 women confirmed these findings. Conclusions: Statin medication use in postmenopausalwomenisassociatedwithanincreasedriskforDM. This may be a medication class effect. Further study by statintypeanddosemayrevealvaryingrisklevelsfornewonset DM in this population.

Controlling Complex Networks: How Much Energy Is Needed?

Abstract: The outstanding problem of controlling complex networks is relevant to many areas of science and engineering, and has the potential to generate technological breakthroughs as well. We address the physically important issue of the energy required for achieving control by deriving and validating scaling laws for the lower and upper energy bounds. These bounds represent a reasonable estimate of the energy cost associated with control, and provide a step forward from the current research on controllability toward ultimate control of complex networked dynamical systems.

GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data

Abstract: Motivation: RNA-seq has been widely used to transcriptome analysis to effectively measure gene expression levels. Although sequencing costs are rapidly decreasing, almost 70% of all the human RNA-seq samples in the Gene Expression Omnibus (GEO) do not have biological replicates and more unreplicated RNA-seq data were published than replicated RNA-seq data in 2011. Despite the large amount of single replicate studies, there is currently no satisfactory method for detecting differentially expressed genes when only a single biological replicate is available. Results: We present the GFOLD (generalized fold change) algorithm to produce biologically meaningful rankings of differentially expressed genes from RNA-seq data. GFOLD assigns reliable statistics for expression changes based on the posterior distribution of log fold change. In this way GFOLD overcomes the shortcomings of p-value and fold change calculated by existing RNA-seq analysis methods and gives more stable and biological meaningful gene rankings when only a single biological replicate is available. Availability: The open source C/C++ program is available at http://www.tongji.edu.cn/~zhanglab/GFOLD/index.html

Correlation Between the Microstructure and Electrical Properties in High‐Performance (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3 Lead‐Free Piezoelectric Ceramics

Abstract: Using three different sintering methods: spark plasma sintering, two-step sintering, and normal sintering (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3 (BCZT) lead-free piezoelectric ceramics with grain sizes in the range of 0.4–32.2 μm were prepared. The effects of grain size on the electrical properties and temperature stability of BCZT ceramics were systematically investigated. Results showed that reducing grain size shifted both the Tc and TT-R to higher temperatures, and tended to enhance the relaxor behavior. A strong dependence of piezoelectric properties on the grain size was observed, and ~10 μm was a critical point for fabricating high-performance BCZT ceramics. For samples with grain sizes >10 μm, excellent piezoelectric properties of kp > 0.48, kt > 0.46, d33 > 470 pC/N and d33* > 950 pm/V were obtained. Moreover, no evident relationship between the grain size and temperature stability existed in this material, and all samples exhibited thermal instability below the Curie temperature. However, increasing grain size was helpful for improving the resistance to thermal depoling. The depolarization was assisted by internal mechanical stresses and the movement of 180° and 90° domain walls, which explained the increased resistance to thermal depoling in coarse-grained samples.

Institution-based barriers to innovation in SMEs in China

Abstract: Despite significant development, small and medium-sized enterprises (SMEs) in China continue to experience institution-based barriers, especially in the area of innovation. What exactly are these barriers? How do these barriers influence innovation? How about the status quo of the institutional environment for SMEs’ innovation and development? We seek to uncover these underexplored areas by developing a model characterized by a cost-risk-opportunity (CRO) innovation triangle. We then enrich this model by interviewing 82 top managers and owners at 41 SMEs. We identify the five key institution-based barriers to innovation in China: (1) competition fairness, (2) access to financing, (3) laws and regulations, (4) tax burden, and (5) support systems. These findings enhance the institution-based view of entrepreneurship by shedding light on how institution-based barriers affect innovation in SMEs.

A Cenozoic record of the equatorial Pacific carbonate compensation depth

Abstract: Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.

Engineered Redox‐Responsive PEG Detachment Mechanism in PEGylated Nano‐Graphene Oxide for Intracellular Drug Delivery

Abstract: In biomedical applications, polyethylene glycol (PEG) functionalization has been a major approach to modify nanocarriers such as nano-graphene oxide for particular biological requirements. However, incorporation of a PEG shell poses a significant diffusion barrier that adversely affects the release of the loaded drugs. This study addresses this critical issue by employing a redox-responsive PEG detachment mechanism. A PEGylated nano-graphene oxide (NGO-SS-mPEG) with redox-responsive detachable PEG shell is developed that can rapidly release an encapsulated payload at tumor-relevant glutathione (GSH) levels. The PEG shell grafted onto NGO sheets gives the nanocomposite high physiological solubility and stability in circulation. It can selectively detach from NGO upon intracellular GSH stimulation. The surface-engineered structures are shown to accelerate the release of doxorubicin hydrochloride (DXR) from NGO-SS-mPEG 1.55 times faster than in the absence of GSH. Confocal microscopy shows clear evidence of NGO-SS-mPEG endocytosis in HeLa cells, mainly accumulated in cytoplasm. Furthermore, upon internalization of DXR-loaded NGO with a disulfide-linked PEG shell into HeLa cells, DXR is effectively released in the presence of an elevated GSH reducing environment, as observed in confocal microscopy and flow cytometric experiments. Importantly, inhibition of cell proliferation is directly correlated with increased intracellular GSH concentrations due to rapid DXR release.

Risk evaluation in failure mode and effects analysis with extended VIKOR method under fuzzy environment

Abstract: Failure mode and effects analysis (FMEA) is a widely used risk assessment tool for defining, identifying, and eliminating potential failures or problems in products, process, designs, and services In traditional FMEA, the risk priorities of failure modes are determined by using risk priority numbers (RPNs), which can be obtained by multiplying the scores of risk factors like occurrence (O), severity (S), and detection (D) However, the crisp RPN method has been criticized to have several deficiencies In this paper, linguistic variables, expressed in trapezoidal or triangular fuzzy numbers, are used to assess the ratings and weights for the risk factors O, S, and D For selecting the most serious failure modes, the extended VIKOR method is used to determine risk priorities of the failure modes that have been identified As a result, a fuzzy FMEA based on fuzzy set theory and VIKOR method is proposed for prioritization of failure modes, specifically intended to address some limitations of the traditional FMEA A case study, which assesses the risk of general anesthesia process, is presented to demonstrate the application of the proposed model under fuzzy environment