A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand‐receptor recognition, ...nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.
The major role of information and communication technology (ICT) in the new economy is well documented: countries worldwide are pouring resources into their ICT infrastructure despite the widely ...acknowledged “productivity paradox”. Evaluating the contribution of ICT investments has become an elusive but important goal of IS researchers and economists. But this area of research is fraught with complexity and we have used Solow's Residual together with time-series analysis tools to overcome some methodological inadequacies of previous studies. Using this approach, we conduct a study of 20 countries to determine if there was empirical evidence to support claims that ICT investments are worthwhile. The results show that ICT contributes to economic growth in many developed countries and newly industrialized economies (NIEs), but not in developing countries. We finally suggest ICT-complementary factors, in an attempt to rectify possible flaws in ICT policies as a contribution towards improvement in global productivity.
Symmetry is a powerful shape regularity that's been exploited by perceptual grouping researchers in both human and computer vision to recover part structure from an image without a priori knowledge ...of scene content. Drawing on the concept of a medial axis, defined as the locus of centers of maximal inscribed discs that sweep out a symmetric part, we model part recovery as the search for a sequence of deformable maximal inscribed disc hypotheses generated from a multiscale super pixel segmentation, a framework proposed by LEV09. However, we learn affinities between adjacent super pixels in a space that's invariant to bending and tapering along the symmetry axis, enabling us to capture a wider class of symmetric parts. Moreover, we introduce a global cost that perceptually integrates the hypothesis space by combining a pair wise and a higher-level smoothing term, which we minimize globally using dynamic programming. The new framework is demonstrated on two datasets, and is shown to significantly outperform the baseline LEV09.
Drosophila Toll-1 and all mammalian Toll-like receptors regulate innate immunity. However, the functions of the remaining eight Toll-related proteins in Drosophila are not fully understood. Here, we ...show that Drosophila Toll-9 is necessary and sufficient for a special form of compensatory proliferation after apoptotic cell loss (undead apoptosis-induced proliferation AiP). Mechanistically, for AiP, Toll-9 interacts with Toll-1 to activate the intracellular Toll-1 pathway for nuclear translocation of the NF-κB-like transcription factor Dorsal, which induces expression of the pro-apoptotic genes reaper and hid. This activity contributes to the feedback amplification loop that operates in undead cells. Given that Toll-9 also functions in loser cells during cell competition, we define a general role of Toll-9 in cellular stress situations leading to the expression of pro-apoptotic genes that trigger apoptosis and apoptosis-induced processes such as AiP. This work identifies conceptual similarities between cell competition and AiP.
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•Toll-9 is required for undead apoptosis-induced proliferation (AiP)•Toll-9 interacts with Toll-1 to activate the intracellular Toll-1 pathway•NF-κB-like transcription factors induce expression of apoptotic genes reaper and hid•Toll-9/Toll-1 signaling establishes an amplification loop for AiP
Shields et al. define a general role of Toll-9 in cellular stress situations leading to the expression of pro-apoptotic genes that trigger apoptosis and apoptosis-induced processes such as apoptosis-induced proliferation. This work identifies conceptual similarities between cell competition and apoptosis-induced proliferation.
Cell banking, disease modeling, and cell therapy applications have placed increasing demands on hiPSC technology. Specifically, the high-throughput derivation of footprint-free hiPSCs and their ...expansion in systems that allow scaled production remains technically challenging. Here, we describe a platform for the rapid, parallel generation, selection, and expansion of hiPSCs using small molecule pathway inhibitors in stage-specific media compositions. The platform supported efficient and expedited episomal reprogramming using just OCT4/SOX2/SV40LT combination (0.5%–4.0%, between days 12 and 16) in a completely feeder-free environment. The resulting hiPSCs are transgene-free, readily cultured, and expanded as single cells while maintaining a homogeneous and genomically stable pluripotent population. hiPSCs generated or maintained in the media compositions described exhibit properties associated with the ground state of pluripotency. The simplicity and robustness of the system allow for the high-throughput generation and rapid expansion of a uniform hiPSC product that is applicable to industrial and clinical-grade use.
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•FRM supports highly efficient minimal factor episomal reprogramming•Clonal derivation of hiPSCs through high-resolution single-cell sorting•FMM supports long-term maintenance of genomically stable, transgene-free hiPSCs•Maintenance of homogeneous pluripotent culture resembling the ground state
Cell therapy and banking applications have placed increasing demands on hiPSC technology. Here, Flynn and colleagues demonstrate a simple multiplex selection and maintenance platform utilizing stage-specific small molecule media additives and flow cytometry sorting to derive minimal factor episomal hiPSCs that are genomically stable and resemble ground state pluripotent stem cells. This platform may serve as a path to generate clinically relevant hiPSCs.
Confined to one cell: A method to detect and isolate single circulating melanoma cells (CMCs; see figure) has been produced by integrating a polymer‐nanofiber‐embedded nanovelcro cell‐affinity assay ...with a laser microdissection (LMD) technique. This method is able to separate CMCs from normal white blood cells (WBCs) and sequence individual cells for a specific mutation related to cancer progression, allowing for more personalized cancer therapy.
This article interprets the work of cultural theorists Steven Connor and Sianne Ngai in terms of their efforts to reevaluate certain key presumptions of aesthetic theory that inherits the ...surprisingly resilient biases of the 18th century, in particular the work of Immanuel Kant and Edmund Burke. Focusing on the work of Ngai and Connor, I think through the implications this recent theory has for the previously peripheral position occupied by gustatory taste and the cultural objects and experiences it implicates. I discuss the possibility that ideas and examples drawn from the work of Connor and Ngai might form the basis for an alternative area of analysis that is better adapted to the peculiarities of gustatory taste and the culinary. In particular, I argue that the visceral element, which tends to accompany gustatory taste, ought to be interpreted in terms of its generative contribution to the creation of concepts through metaphor, rather than as a muddying influence that prevents clarity of discrimination. Similarly, the close relationship between the edible and the domestic is deserving of a more generous reading than is commonly found in aesthetic theory underwritten by the categories of the sublime and the beautiful.
The interval between suspected cancer and diagnosis for symptomatic patients is often fragmented, leading to diagnosis delays and increased patient stress. We conducted an exploratory qualitative ...study to explore barriers and facilitators to implementing and sustaining current initiatives across Canada that optimize early cancer diagnosis, with particular relevance for symptomatic patients.
The national study included a document review and key informant interviews with purposefully recruited participants. Data were analyzed by two researchers using descriptive statistics and thematic analysis.
Twenty-two participants from eight provinces participated in key informant interviews and reported on 17 early cancer diagnosis initiatives. Most initiatives (88%) were in early phases of implementation. Two patient-facing and eight provider/organization barriers to implementation (e.g., lack of stakeholder buy-in and limited resources) and five facilitators for implementation and sustainability were identified. Opportunities to improve early cancer diagnosis initiatives included building relationships with stakeholders, co-creating initiatives, developing initiatives for Indigenous and underserved populations, optimizing efficiency and sustainability, and standardizing metrics to evaluate impact.
Early cancer diagnosis initiatives in Canada are in early implementation phases. Lack of stakeholder buy-in and limited resources pose a challenge to sustainability. We present opportunities for funders and policymakers to optimize the use and potential impact of early cancer diagnosis initiatives.
In Escherichia coli thymidylate synthase (EcTS), rate-determining hydride transfer from the cofactor 5,10-methylene-5,6,7,8-tetrahydrofolate to the intermediate 5-methylene-2′-deoxyuridine ...5′-monophosphate occurs by hydrogen tunneling, requiring precise alignment of reactants and a closed binding cavity, sealed by the C-terminal carboxyl group. Mutations that destabilize the closed conformation of the binding cavity allow small molecules such as β-mercaptoethanol (β-ME) to enter the active site and compete with hydride for addition to the 5-methylene group of the intermediate. The C-terminal deletion mutant of EcTS produced the β-ME adduct in proportions that varied dramatically with cofactor concentration, from 50% at low cofactor concentrations to 0% at saturating cofactor conditions, suggesting communication between active sites. We report the 2.4 Å X-ray structure of the C-terminal deletion mutant of E. coli TS in complex with a substrate and a cofactor analogue, CB3717. The structure is asymmetric, with reactants aligned in a manner consistent with hydride transfer in only one active site. In the second site, CB3717 has shifted to a site where the normal cofactor would be unlikely to form 5-methylene-2′-deoxyuridine 5′-monophosphate, consistent with no formation of the β-ME adduct. The structure shows how the binding of the cofactor at one site triggers hydride transfer and borrows needed stabilization from substrate binding at the second site. It indicates pathways through the dimer interface that contribute to allostery relevant to half-sites reactivity.
•Computational social science supports study of e-commerce policy analytics issues.•Advances have been made for the discovery of new policy-related insights.•Areas covered are: business, consumer and ...social public and private settings.•Machine-based methods are combined with explanatory econometrics and statistics.•Empirical illustrations are in four contemporary e-commerce research issue areas.•Mobile phone stock trading, music popularity, TV viewing, video-on-demand services.
Computational Social Science (CSS) has become a mainstream approach in the empirical study of policy analytics issues in various domains of e-commerce research. This article is intended to represent recent advances that have been made for the discovery of new policy-related insights in business, consumer and social settings. The approach discussed is fusion analytics, which combines machine-based methods from Computer Science (CS) and explanatory empiricism involving advanced Econometrics and Statistics. It explores several efforts to conduct research inquiry in different functional areas of Electronic Commerce and Information Systems (IS), with applications that represent different functional areas of business, as well as individual consumer, social and public issues. Recent developments and shifts in the scientific study of technology-related phenomena and Social Science issues in the presence of historically-large datasets prompt new forms of research inquiry. They include blended approaches to research methodology, and more interest in the production of research results that have direct application to industry contexts. This article showcases the methods shifts and several contemporary applications. They discuss: (1) feedback effects in mobile phone-based stock trading; (2) sustainability of top-rank chart popularity of music tracks; (3) household TV viewing patterns; and (4) household sampling and purchases of video-on-demand (VoD) services. The range of applicability of the ideas goes beyond the scope of these illustrations, to include issues in public services, healthcare, product and service deployment, public opinion and elections, electronic auctions, and travel and tourism services. In fact, the coverage is as broad as for-profit and for-non-profit, private and public, and governmental and non-governmental institutions.
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