Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"Personalised treatment of haematological malignancies through systems medicine based on single molecules in single cells.","authors":"Ehsan Ghayoor Karimiani,&nbsp;Philip Day","doi":"10.1039/c3ib20258e","DOIUrl":"https://doi.org/10.1039/c3ib20258e","url":null,"abstract":"<p><p>Molecular diagnostics in haematological malignancies continues to advance towards more personalized treatment and accordingly demand is increasing for procedures providing quantitative analyses of heterogeneous tissue in malignancies. Circulating leukaemic cells are diverse and comprise discrete clonal populations arising from a common progenitor cell. Some of the current diagnostic techniques possess an attenuated dynamic quantitative range that prevents a clear comprehension of intercellular interactions. Quantitative measurements will facilitate an accurate appreciation of holistic cellular processes, assist with predictions pertaining to perturbations and reveal functional moieties that are truly a facet of the disease, and thus add to current biomarker discovery which often lack assessment of functional involvement in disease mechanisms and processes. This review focuses on quantitative studies related to peripheral blood and haematological malignancies. Data retrieval for either of these diseases is hampered by the high and unchartered degree of heterogeneity typically existing within clinical samples. The likelihood of analysis across single cell populations is highly probable in the near future. This will allow a patient to be readily screened for malignancies and assigned to a risk group based on a quantitative profile of a complex of molecules related to disease. The future analysis of molecular pathology based on detailed molecular dissection looks promising, requiring the integration of various disciplines encompassing morphology, genetics, expression profiling and new and evolving predictive modeling via systems medicine. From this detailed view into patient health, an increasingly personalized treatment plan can be administered, commencing with stratified medicine.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"759-67"},"PeriodicalIF":2.5,"publicationDate":"2013-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib20258e","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40228645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved host-pathogen PPIs. Globally conserved inter-species bacterial PPIs based conserved host-pathogen interactome derived novel target in C. pseudotuberculosis, C. diphtheriae, M. tuberculosis, C. ulcerans, Y. pestis, and E. coli targeted by Piper betel compounds.","authors":"Debmalya Barh,&nbsp;Krishnakant Gupta,&nbsp;Neha Jain,&nbsp;Gourav Khatri,&nbsp;Nidia León-Sicairos,&nbsp;Adrian Canizalez-Roman,&nbsp;Sandeep Tiwari,&nbsp;Ankit Verma,&nbsp;Sachin Rahangdale,&nbsp;Syed Shah Hassan,&nbsp;Anderson Rodrigues dos Santos,&nbsp;Amjad Ali,&nbsp;Luis Carlos Guimarães,&nbsp;Rommel Thiago Jucá Ramos,&nbsp;Pratap Devarapalli,&nbsp;Neha Barve,&nbsp;Marriam Bakhtiar,&nbsp;Ranjith Kumavath,&nbsp;Preetam Ghosh,&nbsp;Anderson Miyoshi,&nbsp;Artur Silva,&nbsp;Anil Kumar,&nbsp;Amarendra Narayan Misra,&nbsp;Kenneth Blum,&nbsp;Jan Baumbach,&nbsp;Vasco Azevedo","doi":"10.1039/c2ib20206a","DOIUrl":"https://doi.org/10.1039/c2ib20206a","url":null,"abstract":"<p><p>Although attempts have been made to unveil protein-protein and host-pathogen interactions based on molecular insights of important biological events and pathogenesis in various organisms, these efforts have not yet been reported in Corynebacterium pseudotuberculosis (Cp), the causative agent of Caseous Lymphadenitis (CLA). In this study, we used computational approaches to develop common conserved intra-species protein-protein interaction (PPI) networks first time for four Cp strains (Cp FRC41, Cp 316, Cp 3/99-5, and Cp P54B96) followed by development of a common conserved inter-species bacterial PPI using conserved proteins in multiple pathogens (Y. pestis, M. tuberculosis, C. diphtheriae, C. ulcerans, E. coli, and all four Cp strains) and E. Coli based experimentally validated PPI data. Furthermore, the interacting proteins in the common conserved inter-species bacterial PPI were used to generate a conserved host-pathogen interaction (HP-PPI) network considering human, goat, sheep, bovine, and horse as hosts. The HP-PPI network was validated, and acetate kinase (Ack) was identified as a novel broad spectrum target. Ceftiofur, penicillin, and two natural compounds derived from Piper betel were predicted to inhibit Ack activity. One of these Piper betel compounds found to inhibit E. coli O157:H7 growth similar to penicillin. The target specificity of these betel compounds, their effects on other studied pathogens, and other in silico results are currently being validated and the results are promising.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"495-509"},"PeriodicalIF":2.5,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20206a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40210556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repositioning through incomplete bi-cliques in an integrated drug-target-disease network.","authors":"Simone Daminelli,&nbsp;V Joachim Haupt,&nbsp;Matthias Reimann,&nbsp;Michael Schroeder","doi":"10.1039/c2ib00154c","DOIUrl":"https://doi.org/10.1039/c2ib00154c","url":null,"abstract":"<p><p>Recently, there has been much interest in gene-disease networks and polypharmacology as a basis for drug repositioning. Here, we integrate data from structural and chemical databases to create a drug-target-disease network for 147 promiscuous drugs, their 553 protein targets, and 44 disease indications. Visualizing and analyzing such complex networks is still an open problem. We approach it by mining the network for network motifs of bi-cliques. In our case, a bi-clique is a subnetwork in which every drug is linked to every target and disease. Since the data are incomplete, we identify incomplete bi-cliques, whose completion introduces novel, predicted links from drugs to targets and diseases. We demonstrate the power of this approach by repositioning cardiovascular drugs to parasitic diseases, by predicting the cancer-related kinase PIK3CG as a novel target of resveratrol, and by identifying for five drugs a shared binding site in four serine proteases and novel links to cancer, cardiovascular, and parasitic diseases.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"778-88"},"PeriodicalIF":2.5,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib00154c","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40186672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is newer better?--evaluating the effects of data curation on integrated analyses in Saccharomyces cerevisiae.","authors":"Katherine James, Anil Wipat, Jennifer Hallinan","doi":"10.1039/c2ib00123c","DOIUrl":"10.1039/c2ib00123c","url":null,"abstract":"<p><p>Recent high-throughput experiments have produced a wealth of heterogeneous datasets, each of which provides information about different aspects of the cell. Consequently, integration of diverse data types is essential in order to address many biological questions. The quality of any integrated analysis system is dependent upon the quality of its component data, and upon the Gold Standard data used to evaluate it. It is commonly assumed that the quality of data improves as databases grow and change, particularly for manually curated databases. However, the validity of this assumption can be questioned, given the constant changes in the data coupled with the high level of noise associated with high-throughput experimental techniques. One of the most powerful approaches to data integration is the use of Probabilistic Functional Integrated Networks (PFINs). Here, we systematically analyse the changes in four highly-curated and widely-used online databases and evaluate the extent to which these changes affect the protein function prediction performance of PFINs in the yeast Saccharomyces cerevisiae. We find that the global trend in network performance improves over time. Where individual areas of biology are concerned, however, the most recent files do not always produce the best results. Individual datasets have unique biases towards different biological processes and by selecting and integrating relevant datasets performance can be improved. When using any type of integrated system to answer a specific biological question careful selection of raw data and Gold Standard is vital, since the most recent data may not be the most appropriate.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"715-27"},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40177395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.","authors":"Dooyoung Lee,&nbsp;Jiyeon Kim,&nbsp;Michael T Beste,&nbsp;Gary A Koretzky,&nbsp;Daniel A Hammer","doi":"10.1039/c2ib00002d","DOIUrl":"https://doi.org/10.1039/c2ib00002d","url":null,"abstract":"<p><p>T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"606-14"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib00002d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40548667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation, characterization, and surface immobilization of native vesicles obtained by mechanical extrusion of mammalian cells.","authors":"Huawen Wu,&nbsp;Ann E Oliver,&nbsp;Viviane N Ngassam,&nbsp;Chanel K Yee,&nbsp;Atul N Parikh,&nbsp;Yin Yeh","doi":"10.1039/c2ib20022h","DOIUrl":"https://doi.org/10.1039/c2ib20022h","url":null,"abstract":"<p><p>Native vesicles or \"reduced protocells\" derived by mechanical extrusion concentrate selected plasma membrane components, while downsizing complexities of whole cells. We illustrate this technique, characterize the physical-chemical properties of these reduced configurations of whole cells, and demonstrate their surface immobilization and patternability. This simple detergent-free vesicularized membrane preparation should prove useful in fundamental studies of cellular membranes, and may provide a means to engineer therapeutic cells and enable high-throughput devices containing near-native, functional proteolipidic assemblies.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"685-92"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20022h","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40191670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of morphogenesis and neural differentiation of human mesenchymal stem cells using carbon nanotube sheets.","authors":"Jeong Ah Kim,&nbsp;Eui Yun Jang,&nbsp;Tae June Kang,&nbsp;Sungjun Yoon,&nbsp;Raquel Ovalle-Robles,&nbsp;Won Jong Rhee,&nbsp;Taewoo Kim,&nbsp;Ray H Baughman,&nbsp;Yong Hyup Kim,&nbsp;Tai Hyun Park","doi":"10.1039/c2ib20017a","DOIUrl":"https://doi.org/10.1039/c2ib20017a","url":null,"abstract":"<p><p>In order to successfully utilize stem cells for therapeutic applications in regenerative medicine, efficient differentiation into a specific cell lineage and guidance of axons in a desired direction is crucial. Here, we used aligned multi-walled carbon nanotube (MWCNT) sheets to differentiate human mesenchymal stem cells (hMSCs) into neural cells. Human MSCs present a preferential adhesion to aligned CNT sheets with longitudinal stretch parallel to the CNT orientation direction. Cell elongation was 2-fold higher than the control and most of the cells were aligned on CNT sheets within 5° from the CNT orientation direction. Furthermore, a significant, synergistic enhancement of neural differentiation was observed in hMSCs cultured on the CNT sheets. Axon outgrowth was also controlled using nanoscale patterning of CNTs. This CNT sheet provides a new cellular scaffold platform that can regulate morphogenesis and differentiation of stem cells, which could open up a new approach for tissue and stem cell regeneration.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"587-94"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20017a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40182246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RhoA-induced cytoskeletal tension controls adaptive cellular remodeling to mechanical signaling.","authors":"Soon-Mi Lim,&nbsp;Jerome P Trzeciakowski,&nbsp;Harini Sreenivasappa,&nbsp;Lawrence J Dangott,&nbsp;Andreea Trache","doi":"10.1039/c2ib20008b","DOIUrl":"https://doi.org/10.1039/c2ib20008b","url":null,"abstract":"<p><p>The ability to measure real-time mechanosensitive events at the subcellular level in response to discrete mechanical stimulation is a critical component in understanding mechanically-induced cellular remodeling. Vascular smooth muscle cells (VSMC) were transfected with RhoA constructs (wild type, dominant negative or constitutively active) or treated with ML-7 to induce specific cytoskeletal tension characteristics prior to mechanical stimulation. Tensile stress was applied to live VSMC using an atomic force microscope probe functionalized with extracellular matrix (ECM) proteins. The ECM induces selective integrin activation and focal adhesion formation, enabling direct manipulation of cortical actin through an active ECM-integrin-actin linkage. Therefore, locally induced mechanosensitive events triggered downstream activation of intracellular signaling pathways responsible for actin and focal adhesion remodeling throughout the cell. Integration of mechanical stimulation with simultaneous fluorescence imaging by spinning-disk confocal and total internal reflection fluorescence microscopy enabled visualization and quantification of molecular dynamic events at the sub-cellular level in real-time. Results provide evidence that the pre-existing cytoskeletal tension affects the actomyosin apparatus which in turn coordinates the ability of the cell to adapt to the externally applied stress. RhoA activation induced high cytoskeletal tension that correlated with increased stress fiber formation, cell stiffness, integrin activation and myosin phosphorylation. In contrast, blocking Rho-kinase or myosin function was characterized by low cytoskeletal tension with a decreased level of stress fiber formation, lower cell stiffness and integrin activation. Our findings show that VSMC sense and adapt to physical microenvironmental changes by a coordinated response of the actomyosin apparatus necessary to establish a new homeostatic state.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"615-27"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20008b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40550157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A plant virus substrate induces early upregulation of BMP2 for rapid bone formation.","authors":"Pongkwan Sitasuwan,&nbsp;L Andrew Lee,&nbsp;Peng Bo,&nbsp;Erin N Davis,&nbsp;Yuan Lin,&nbsp;Qian Wang","doi":"10.1039/c2ib20041d","DOIUrl":"https://doi.org/10.1039/c2ib20041d","url":null,"abstract":"<p><p>Many nanoscale materials have been developed to investigate the effects on stem cell differentiations via topographical and chemical cues for applications in tissue engineering and regenerative medicine. The use of plant viruses as cell supporting substrates has been of particular interest due to the rapid induction of bone marrow derived mesenchymal stem cells (BMSCs) towards osteogenic cells. In this study, the role of Tobacco mosaic virus (TMV) and its early effects on osteoinduction with particular emphasis on the regulation of bone morphogenetic protein-2 (BMP2) was examined. We observed that the cells on the virus substrate immediately aggregated and formed bone-like nodules within 24 hours. An immediate increase in BMP2 gene and protein expression for cells on the TMV substrate was observed within 8 hours of osteoinduction. Moreover, BMP2 expression was highly localized to cells within the cell aggregates. This enhanced differentiation only occurred when TMV was coated on a solid support but not upon adding the virus to the media solution. Taken together, the results from this study highlight the potential of virus-based nanomaterials to promote endogenous BMP2 production which may prove to be a unique approach to studying the regulatory mechanisms involved in early osteoblastic differentiation.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"651-60"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20041d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40181618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts.","authors":"Shijun Zhu,&nbsp;Terry W Moore,&nbsp;Xiaoqian Lin,&nbsp;Nao Morii,&nbsp;Alessandra Mancini,&nbsp;Randy B Howard,&nbsp;Deborah Culver,&nbsp;Richard F Arrendale,&nbsp;Prabhakar Reddy,&nbsp;Taylor J Evers,&nbsp;Hongzheng Zhang,&nbsp;Gabriel Sica,&nbsp;Zhuo G Chen,&nbsp;Aiming Sun,&nbsp;Haian Fu,&nbsp;Fadlo R Khuri,&nbsp;Dong M Shin,&nbsp;James P Snyder,&nbsp;Mamoru Shoji","doi":"10.1039/c2ib20007d","DOIUrl":"https://doi.org/10.1039/c2ib20007d","url":null,"abstract":"<p><p>Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5-6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg kg(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 μg mL(-1) or <32 and 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"633-40"},"PeriodicalIF":2.5,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c2ib20007d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40180941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}