Quantum Computing: Principles and Applications

The development of quantum computers over the past few years is probably one of the significant advancements in the history of quantum computing. D-Wave quantum computer has been available for more than eight years. IBM has made its quantum computer accessible via its cloud service. Also, Microsoft, Google, Intel, and NASA have been heavily investing in the development of quantum computers and their applications. The quantum computer seems to be no longer just for physicists and computer scientists but also for information system researchers. This paper introduces the basic concepts of quantum computing and describes well-known quantum applications for non-physicists. Also, the current status of the developments in quantum computing is presented

Exploring and Evaluating E-Business Models: A Preliminary Study of a Community-Based Website

Social media is the use of the Internet and mobile technologies to share user-generated content. At a broader level, social media has been providing an increasing amount of the information that is presented to very wide audiences. However, hyper-local media is a form of such social media that tries to target a comparably narrow but focused group of audience with timely and related content. OpenAnchorage presents our vision of a hyper-local information site. It was developed to collect community information created by the local providers and present this information on a local area map where interested users can select the data relevant to their hyper-local geographic area. OpenAnchorage website simultaneously requires a process of providing both new technology and new content. The research design is an iterative analysis-adjustment and adaption-data collection with an integrated process of using Business Model Canvas and Customer Development Stack. The goal of this project is to determine the potential business model or models that will serve our site best by using this innovative, iterative, experiment approach. The desire is that, eventually, the site will be able to get a critical mass of participation, to generate socio-economic values to serve our community, and to support its own long-term sustainability

Myxoid liposarcoma-associated EWSR1-DDIT3 selectively represses osteoblastic and chondrocytic transcription in multipotent mesenchymal cells.

BACKGROUND: Liposarcomas are the most common class of soft tissue sarcomas, and myxoid liposarcoma is the second most common liposarcoma. EWSR1-DDIT3 is a chimeric fusion protein generated by the myxoid liposarcoma-specific chromosomal translocation t(12;22)(q13;q12). Current studies indicate that multipotent mesenchymal cells are the origin of sarcomas. The mechanism whereby EWSR1-DDIT3 contributes to the phenotypic selection of target cells during oncogenic transformation remains to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Reporter assays showed that the EWSR1-DDIT3 myxoid liposarcoma fusion protein, but not its wild-type counterparts EWSR1 and DDIT3, selectively repressed the transcriptional activity of cell lineage-specific marker genes in multipotent mesenchymal C3H10T1/2 cells. Specifically, the osteoblastic marker Opn promoter and chondrocytic marker Col11a2 promoter were repressed, while the adipocytic marker Ppar-γ2 promoter was not affected. Mutation analyses, transient ChIP assays, and treatment of cells with trichostatin A (a potent inhibitor of histone deacetylases) or 5-Aza-2'-deoxycytidine (a methylation-resistant cytosine homolog) revealed the possible molecular mechanisms underlying the above-mentioned selective transcriptional repression. The first is a genetic action of the EWSR1-DDIT3 fusion protein, which results in binding to the functional C/EBP site within Opn and Col11a2 promoters through interaction of its DNA-binding domain and subsequent interference with endogenous C/EBPβ function. Another possible mechanism is an epigenetic action of EWSR1-DDIT3, which enhances histone deacetylation, DNA methylation, and histone H3K9 trimethylation at the transcriptional repression site. We hypothesize that EWSR1-DDIT3-mediated transcriptional regulation may modulate the target cell lineage through target gene-specific genetic and epigenetic conversions. CONCLUSIONS/SIGNIFICANCE: This study elucidates the molecular mechanisms underlying EWSR1-DDIT3 fusion protein-mediated phenotypic selection of putative target multipotent mesenchymal cells during myxoid liposarcoma development. A better understanding of this process is fundamental to the elucidation of possible direct lineage reprogramming in oncogenic sarcoma transformation mediated by fusion proteins

Protein expression by each FLAG-tagged expression vector.

<p>Western blotting using an antibody against the N-terminal FLAG epitope tag. Each protein band is indicated by an asterisk (*).</p

Innate mouse multipotent mesenchymal C3H10T1/2 cells expressed multiple lineage-specific marker genes.

<p>RT-PCR analysis detected osteoblastic marker Opn (lane 1), chondrocytic marker Col11a2 (lane 3), and adipocytic marker Ppar-γ (lane 5) mRNA transcripts in C3H10T1/2 cells. Mouse osteosarcoma cell line LM8 (lane 2), mouse embryonic skeleton cells (lane 4), and mouse preadipocytic cell line 3T3-L1 (lane 6) were analyzed as positive controls for Opn, Col11a2, and Ppar-γ gene expression, respectively. The β-actin transcript level served as a loading control for each reaction.</p

Interaction of EWSR1-DDIT3 and potential C/EBP-binding sites within Opn and Col11a2 promoters <i>in vivo</i>.

<p>Transient ChIP assays using an antibody against the N-terminal FLAG epitope or normal IgG. C3H10T1/2 cells were transfected with Opn (<b>A</b>) or Col11a2 (<b>B</b>) luciferase reporter plasmids plus FLAG-tagged expression vectors. Promoter DNA fragments containing potential C/EBP-binding sites (open box) were immunoprecipitated with EWSR1-DDIT3 when wild-type Opn (pGL3-Opn) and Col11a2 (pGL3-Col11a2) promoter constructs were analyzed. Either deleting (EWSR1-DDIT3 del LZ, broken line) or mutating (EWSR1-DDIT3 mut LZ, filled box) the LZ dimer forming domain of EWSR1-DDIT3 or mutating potential C/EBP-binding sites within Opn (inverted CCAAT box, pGL3-Opn mut, filled box) and Col11a2 (half C/EBP site, pGL3-Col11a2 mut, filled box) promoters eliminated the protein–DNA interaction. As indicated by the arrows, the forward PCR primers are promoter sequence-specific primers and locate upstream to the potential C/EBP-binding site (open box), while the reverse PCR primer pGL3 is a plasmid-specific primer.</p

EWSR1-DDIT3 affected recruitment of endogenous C/EBPβ to the C/EBP site within Opn and Col11a2 promoters.

<p>Transient ChIP assays using an antibody against C/EBPα, C/EBPβ, or normal IgG. C3H10T1/2 cells were transfected with Opn (<b>A</b>) and Col11a2 (<b>B</b>) luciferase reporter plasmids plus EWSR1-DDIT3 expression vectors. Promoter DNA fragments containing the C/EBP site (open box) were immunoprecipitated with an antibody against C/EBPα or C/EBPβ. Relative values reflecting protein–DNA interactions were calculated by adjusting corresponding signal intensities to those of input levels. Experiments in duplicate were repeated at least three times, and the results are shown as averages below each band. For C/EBPβ, the relative value of immunoprecipitated Opn and Col11a2 promoter fragments significantly decreased after EWSR1-DDIT3 overexpression from 0.71 to 0.30 and 0.76 to 0.35, respectively. Asterisks (*) indicate statistical significance (<i>p</i><0.05) calculated by unpaired <i>t</i>-test, with <i>p</i> values of 0.022 for Opn and 0.0025 for Col11a2. As indicated by the arrows, the forward PCR primers are promoter sequence-specific primers and locate upstream to the C/EBP site (open box), while the reverse PCR primer pGL3 is a plasmid-specific primer.</p

Identification of potential C/EBP-binding sites within Opn and Col11a2 promoters in C3H10T1/2 cells.

<p>(<b>A</b>) An inverted CCAAT box (boxed) of the pGL3-Opn promoter construct was mutated as designated to produce pGL3-Opn mut. The pGL3-Opn mut exhibited significantly reduced promoter activity. (<b>B</b>) A half C/EBP site (boxed) of the pGL3-Col11a2 promoter construct was mutated as designated to produce pGL3-Col11a2 mut. The pGL3-Col11a2 mut exhibited significantly reduced promoter activity. (<b>C</b>) The pGL3-Ppar-γ2 promoter construct containing tandem repeats of C/EBP-binding sites (boxed) and its deletion mutants, pGL3-334 (lacking the distal C/EBP binding site I) and pGL3-320 (lacking both C/EBP-binding sites I and II), exhibited comparable activity. The luciferase activities were expressed as fold inductions; each activity relative to that of the promoter-less reporter vector (pGL3 basic). Transfection in duplicate was repeated at least three times, and the results are shown as averages ± SE. Asterisks (*) indicate statistical significance (<i>p</i><0.05) calculated by unpaired t-test.</p