Assembling of G-strands into novel tetra-molecular parallel G4-DNA nanostructures using avidin–biotin recognition

We describe a method for the preparation of novel long (hundreds of nanometers), uniform, inter-molecular G4-DNA molecules composed of four parallel G-strands. The only long continuous G4-DNA reported so far are intra-molecular structures made of a single G-strand. To enable a tetra-molecular assembly of the G-strands we developed a novel approach based on avidin–biotin biological recognition. The steps of the G4-DNA production include: (i) Enzymatic synthesis of long poly(dG)-poly(dC) molecules with biotinylated poly(dG)-strand; (ii) Formation of a complex between avidin-tetramer and four biotinylated poly(dG)-poly(dC) molecules; (iii) Separation of the poly(dC) strands from the poly(dG)-strands, which are connected to the avidin; (iv) Assembly of the four G-strands attached to the avidin into tetra-molecular G4-DNA. The average contour length of the formed structures, as measured by AFM, is equal to that of the initial poly(dG)-poly(dC) molecules, suggesting a tetra-molecular mechanism of the G-strands assembly. The height of tetra-molecular G4-nanostructures is larger than that of mono-molecular G4-DNA molecules having similar contour length. The CD spectra of the tetra- and mono-molecular G4-DNA are markedly different, suggesting different structural organization of these two types of molecules. The tetra-molecular G4-DNA nanostructures showed clear electrical polarizability. This suggests that they may be useful for molecular electronics

Reducing uncertainty in health-care resource allocation

A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful

Switching Transport through Nanopores with pH-Responsive Polymer Brushes for Controlled Ion Permeability

Several nanoporous platforms were functionalized with pH-responsive poly(methacrylic acid) (PMAA) brushes using surface-initiated atom transfer radical polymerization (SI-ATRP). The growth of the PMAA brush and its pH-responsive behavior from the nanoporous platforms were confirmed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). The swelling behavior of the pH-responsive PMAA brushes grafted only from the nanopore walls was investigated by AFM in aqueous liquid environment with pH values of 4 and 8. AFM images displayed open nanopores at pH 4 and closed ones at pH 8, which rationalizes their use as gating platforms. Ion conductivity across the nanopores was investigated with current–voltage measurements at various pH values. Enhanced higher resistance across the nanopores was observed in a neutral polymer brush state (lower pH values) and lower resistance when the brush was charged (higher pH values). By adding a fluorescent dye in an environment of pH 4 or pH 8 at one side of the PMAA-brush functionalized nanopore array chips, diffusion across the nanopores was followed. These experiments displayed faster diffusion rates of the fluorescent molecules at pH 4 (PMAA neutral state, open pores) and slower diffusion at pH 8 (PMAA charged state, closed pores) showing the potential of this technology toward nanoscale valve applications

Advances in the treatment of chronic myeloid leukemia

Although imatinib is firmly established as an effective therapy for newly diagnosed patients with chronic myeloid leukemia (CML), the field continues to advance on several fronts. In this minireview we cover recent results of second generation tyrosine kinase inhibitors in newly diagnosed patients, investigate the state of strategies to discontinue therapy and report on new small molecule inhibitors to tackle resistant disease, focusing on agents that target the T315I mutant of BCR-ABL. As a result of these advances, standard of care in frontline therapy has started to gravitate toward dasatinib and nilotinib, although more observation is needed to fully support this. Stopping therapy altogether remains a matter of clinical trials, and more must be learned about the mechanisms underlying the persistence of leukemic cells with treatment. However, there is good news for patients with the T315I mutation, as effective drugs such as ponatinib are on their way to regulatory approval. Despite these promising data, accelerated or blastic phase disease remains a challenge, possibly due to BCR-ABL-independent resistance

DMSO and Betaine Greatly Improve Amplification of GC-Rich Constructs in De Novo Synthesis

In Synthetic Biology, de novo synthesis of GC-rich constructs poses a major challenge because of secondary structure formation and mispriming. While there are many web-based tools for codon optimizing difficult regions, no method currently exists that allows for potentially phenotypically important sequence conservation. Therefore, to overcome these limitations in researching GC-rich genes and their non-coding elements, we explored the use of DMSO and betaine in two conventional methods of assembly and amplification. For this study, we compared the polymerase (PCA) and ligase-based (LCR) methods for construction of two GC-rich gene fragments implicated in tumorigenesis, IGF2R and BRAF. Though we found no benefit in employing either DMSO or betaine during the assembly steps, both additives greatly improved target product specificity and yield during PCR amplification. Of the methods tested, LCR assembly proved far superior to PCA, generating a much more stable template to amplify from. We further report that DMSO and betaine are highly compatible with all other reaction components of gene synthesis and do not require any additional protocol modifications. Furthermore, we believe either additive will allow for the production of a wide variety of GC-rich gene constructs without the need for expensive and time-consuming sample extraction and purification prior to downstream application

Epigenetic reprogramming of breast cancer cells with oocyte extracts

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.</p> <p>Results</p> <p>We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.</p> <p>Conclusions</p> <p>This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.</p

An enterprise engineering approach for the alignment of business and information technology strategy

Information systems and information technology (IS/IT, hereafter just IT) strategies usually depend on a business strategy. The alignment of both strategies improves their strategic plans. From an external perspective, business and IT alignment is the extent to which the IT strategy enables and drives the business strategy. This article reviews strategic alignment between business and IT, and proposes the use of enterprise engineering (EE) to achieve this alignment. The EE approach facilitates the definition of a formal dialog in the alignment design. In relation to this, new building blocks and life-cycle phases have been defined for their use in an enterprise architecture context. This proposal has been adopted in a critical process of a ceramic tile company for the purpose of aligning a strategic business plan and IT strategy, which are essential to support this process. © 2011 Taylor & Francis.Cuenca, L.; Boza, A.; Ortiz, A. (2011). An enterprise engineering approach for the alignment of business and information technology strategy. International Journal of Computer Integrated Manufacturing. 24(11):974-992. https://doi.org/10.1080/0951192X.2011.579172S9749922411(1993). CIMOSA: Open System Architecture for CIM. doi:10.1007/978-3-642-58064-2Ang, J., Shaw, N., & Pavri, F. (1995). Identifying strategic management information systems planning parameters using case studies. International Journal of Information Management, 15(6), 463-474. doi:10.1016/0268-4012(95)00049-dAvison, D., Jones, J., Powell, P., & Wilson, D. (2004). Using and validating the strategic alignment model. The Journal of Strategic Information Systems, 13(3), 223-246. doi:10.1016/j.jsis.2004.08.002Avgerou, & McGrath. (2007). Power, Rationality, and the Art of Living through Socio-Technical Change. MIS Quarterly, 31(2), 295. doi:10.2307/25148792Bergeron, F., Raymond, L., & Rivard, S. (2004). Ideal patterns of strategic alignment and business performance. Information & Management, 41(8), 1003-1020. doi:10.1016/j.im.2003.10.004Bernus, P., Nemes, L., & Schmidt, G. (Eds.). (2003). Handbook on Enterprise Architecture. doi:10.1007/978-3-540-24744-9Bleistein, S. J., Cox, K., Verner, J., & Phalp, K. T. (2006). B-SCP: A requirements analysis framework for validating strategic alignment of organizational IT based on strategy, context, and process. Information and Software Technology, 48(9), 846-868. doi:10.1016/j.infsof.2005.12.001Buchanan, S., & Gibb, F. (1998). The information audit: An integrated strategic approach. International Journal of Information Management, 18(1), 29-47. doi:10.1016/s0268-4012(97)00038-8Buchanan, S., & Gibb, F. (2007). The information audit: Role and scope. International Journal of Information Management, 27(3), 159-172. doi:10.1016/j.ijinfomgt.2007.01.002Chen, D., & Vernadat, F. (2004). Standards on enterprise integration and engineering—state of the art. International Journal of Computer Integrated Manufacturing, 17(3), 235-253. doi:10.1080/09511920310001607087Chen, D., Doumeingts, G., & Vernadat, F. (2008). Architectures for enterprise integration and interoperability: Past, present and future. Computers in Industry, 59(7), 647-659. doi:10.1016/j.compind.2007.12.016Chen, H.-M., Kazman, R., & Garg, A. (2005). BITAM: An engineering-principled method for managing misalignments between business and IT architectures. Science of Computer Programming, 57(1), 5-26. doi:10.1016/j.scico.2004.10.002Cuenca, L., Ortiz, A., & Vernadat, F. (2006). From UML or DFD models to CIMOSA partial models and enterprise components. International Journal of Computer Integrated Manufacturing, 19(3), 248-263. doi:10.1080/03081070500065841Davis, G. B. (2000). Information Systems Conceptual Foundations: Looking Backward and Forward. IFIP Advances in Information and Communication Technology, 61-82. doi:10.1007/978-0-387-35505-4_5Gindy, N., Morcos, M., Cerit, B., & Hodgson, A. (2008). Strategic technology alignment roadmapping STAR® aligning R&D investments with business needs. International Journal of Computer Integrated Manufacturing, 21(8), 957-970. doi:10.1080/09511920801927148Goethals, F. G., Lemahieu, W., Snoeck, M., & Vandenbulcke, J. A. (2007). The data building blocks of the enterprise architect. Future Generation Computer Systems, 23(2), 269-274. doi:10.1016/j.future.2006.05.004Greefhorst, D., Koning, H., & Vliet, H. van. (2006). The many faces of architectural descriptions. Information Systems Frontiers, 8(2), 103-113. doi:10.1007/s10796-006-7975-xGregor, S., Hart, D., & Martin, N. (2007). Enterprise architectures: enablers of business strategy and IS/IT alignment in government. Information Technology & People, 20(2), 96-120. doi:10.1108/09593840710758031Hartono, E., Lederer, A. L., Sethi, V., & Zhuang, Y. (2003). Key predictors of the implementation of strategic information systems plans. ACM SIGMIS Database, 34(3), 41-53. doi:10.1145/937742.937747Henderson, J. C., & Venkatraman, H. (1993). Strategic alignment: Leveraging information technology for transforming organizations. IBM Systems Journal, 32(1), 472-484. doi:10.1147/sj.382.0472Hirschheim, R., & Sabherwal, R. (2001). Detours in the Path toward Strategic Information Systems Alignment. California Management Review, 44(1), 87-108. doi:10.2307/41166112Hoogervorst, J. A. P. (2009). Enterprise Governance and Enterprise Engineering. doi:10.1007/978-3-540-92671-9Johnson, A. M., & Lederer, A. L. (2010). CEO/CIO mutual understanding, strategic alignment, and the contribution of IS to the organization. Information & Management, 47(3), 138-149. doi:10.1016/j.im.2010.01.002JONKERS, H., LANKHORST, M., VAN BUUREN, R., HOPPENBROUWERS, S., BONSANGUE, M., & VAN DER TORRE, L. (2004). CONCEPTS FOR MODELING ENTERPRISE ARCHITECTURES. International Journal of Cooperative Information Systems, 13(03), 257-287. doi:10.1142/s0218843004000985King, W. R. (1978). Strategic Planning for Management Information Systems. MIS Quarterly, 2(1), 27. doi:10.2307/249104Leonard, J. (2007). Sharing a Vision: comparing business and IS managers’ perceptions of strategic alignment issues. Australasian Journal of Information Systems, 15(1). doi:10.3127/ajis.v15i1.299Luftman, J. N., Lewis, P. R., & Oldach, S. H. (1993). Transforming the enterprise: The alignment of business and information technology strategies. IBM Systems Journal, 32(1), 198-221. doi:10.1147/sj.321.0198Luftman, J., Ben-Zvi, T., Dwivedi, R., & Rigoni, E. H. (2010). IT Governance. International Journal of IT/Business Alignment and Governance, 1(2), 13-25. doi:10.4018/jitbag.2010040102Melville, Kraemer, & Gurbaxani. (2004). Review: Information Technology and Organizational Performance: An Integrative Model of IT Business Value. MIS Quarterly, 28(2), 283. doi:10.2307/25148636Newkirk, H. E., & Lederer, A. L. (2006). Incremental and Comprehensive Strategic Information Systems Planning in an Uncertain Environment. IEEE Transactions on Engineering Management, 53(3), 380-394. doi:10.1109/tem.2006.877446Noran, O. (2003). An analysis of the Zachman framework for enterprise architecture from the GERAM perspective. Annual Reviews in Control, 27(2), 163-183. doi:10.1016/j.arcontrol.2003.09.002Noran, O. (2005). A systematic evaluation of the C4ISR AF using ISO15704 Annex A (GERAM). Computers in Industry, 56(5), 407-427. doi:10.1016/j.compind.2004.12.005Ortiz, A., Lario, F., & Ros, L. (1999). Enterprise Integration—Business Processes Integrated Management: a proposal for a methodology to develop Enterprise Integration Programs. Computers in Industry, 40(2-3), 155-171. doi:10.1016/s0166-3615(99)00021-4Panetto, H., Baïna, S., & Morel, G. (2007). Mapping the IEC 62264 models onto the Zachman framework for analysing products information traceability: a case study. Journal of Intelligent Manufacturing, 18(6), 679-698. doi:10.1007/s10845-007-0040-xPapp, R. (Ed.). (2001). Strategic Information Technology. doi:10.4018/978-1-87828-987-2Peñaranda, N., Mejía, R., Romero, D., & Molina, A. (2010). Implementation of product lifecycle management tools using enterprise integration engineering and action-research. International Journal of Computer Integrated Manufacturing, 23(10), 853-875. doi:10.1080/0951192x.2010.495136Reich, B. H., & Benbasat, I. (2000). Factors That Influence the Social Dimension of Alignment between Business and Information Technology Objectives. MIS Quarterly, 24(1), 81. doi:10.2307/3250980Sledgianowski, D., & Luftman, J. (2005). IT-Business Strategic Alignment Maturity. Journal of Cases on Information Technology, 7(2), 102-120. doi:10.4018/jcit.2005040107Sowa, J. F., & Zachman, J. A. (1992). Extending and formalizing the framework for information systems architecture. IBM Systems Journal, 31(3), 590-616. doi:10.1147/sj.313.0590Van Grembergen, W., & De Haes, S. (2010). A Research Journey into Enterprise Governance of IT, Business/IT Alignment and Value Creation. International Journal of IT/Business Alignment and Governance, 1(1), 1-13. doi:10.4018/jitbag.2010120401Xueying Wang, Xiongwei Zhou, & Longbin Jiang. (2008). A method of business and IT alignment based on Enterprise Architecture. 2008 IEEE International Conference on Service Operations and Logistics, and Informatics. doi:10.1109/soli.2008.468649