1,722,493 research outputs found
Mass Action at the Single-Molecule Level
No full textWe developed a system to reversibly encapsulate small numbers of molecules in an array of nanofabricated "dimples". This system enables highly parallel, long-term, and attachment-free studies of molecular dynamics via single-molecule fluorescence. In studies of bimolecular reactions of small numbers of confined molecules, we see phenomena that, while expected from basic statistical mechanics, are not observed in bulk chemistry. Statistical fluctuations in the occupancy of sealed reaction chambers lead to steady-state fluctuations in reaction equilibria and rates. These phenomena are likely to be important whenever reactions happen in confined geometries.11Nsciescopu
Focused clamping of a single neuronal SNARE complex by complexin under high mechanical tension
No full textNeuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) catalyze synaptic vesicle fusion with presynaptic membranes through the formation of SNARE complexes. Complexin (Cpx) is the only presynaptic protein that tightly binds to SNAREs and regulates membrane fusion, but how it modulates the energy landscape of SNARE complex assembly, especially under mechanical tension on the complex, remains unclear. Here, using magnetic tweezers, we report how Cpx interacts with single SNARE complexes. The effects of Cpx manifest only under high mechanical tensions above 13 pN. Cpx stabilizes the central four-helix bundle of SNARE motifs and, at the same time, prevents the complete zippering of SNAREs by inhibiting linker-domain assembly. These results suggest that Cpx generates a focused clamp for the neuronal SNARE complex in a linker-open conformation. Our results provide a hint as to how Cpx cooperates with neuronal SNAREs to prime synaptic vesicles in preparation for synchronous neurotransmitter release.11Nsciescopu
Nano-mechanical measurements of protein-DNA interactions with a silicon nitride pulley
No full textProteins adhere to DNA at locations and with strengths that depend on the protein conformation, the underlying DNA sequence and the ionic content of the solution. A facile technique to probe the positions and strengths of protein-DNA binding would aid in understanding these important interactions. Here, we describe a ‘DNA pulley’ for position-resolved nano-mechanical measurements of protein-DNA interactions. A molecule of λ DNA is tethered by one end to a glass surface, and by the other end to a magnetic bead. The DNA is stretched horizontally by a magnet, and a nanoscale knife made of silicon nitride is manipulated to contact, bend and scan along the DNA. The mechanical profile of the DNA at the contact with the knife is probed via nanometer-precision optical tracking of the magnetic bead. This system enables detection of protein bumps on the DNA and localization of their binding sites. We study theoretically the technical requirements to detect mechanical heterogeneities in the DNA itself.Version of Recor
Tension exerted on cells by magnetic nanoparticles regulates differentiation of human mesenchymal stem cells
No full textCells can ???sense??? physical cues in the surrounding microenvironment and ???react??? by changing their function. Previous studies have focused on regulating the physical properties of the matrix, such as stiffness and topog-raphy, thus changing the tension ???felt??? by the cell as a result. In this study, by directly applying a quantified magnetic force to the cell, a correlation between differentiation and tension was shown. The magnetic force, quantified by magnetic tweezers, was applied by incorporating magnetotactic bacteria-isolated magnetic nanoparticles (MNPs) in human mesenchymal stem cells. As the applied tension increased, the expression levels of osteogenic differentiation marker genes and proteins were proportionally upregulated. Additionally, the translocation of YAP and RUNX2, deformation of nucleus, and activation of the MAPK signaling pathway were observed in tension-based osteogenic differentiation. Our findings provide a platform for the quantitative control of tension, a key factor in stem cell differentiation, between cells and the matrix using MNPs. Furthermore, these findings improve the understanding of osteogenic differentiation by mechanotransduction.11Nsciescopu
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Application of Axiomatic Design Theory and Conflict Techniques for the Design of Intersections: Part 1
No full textA non-invasive approach to the resistive switching physical model of ultra-thin organic–inorganic dielectric-based ReRAMs
No full textThe race to next-generation non-volatile memory is on, and ultra-thin (<5 nm) organic–inorganic hybrid dielectric-based ReRAMs are a top contender. However, their extremely small thickness hinders their processability through material characterization techniques, leaving gaps in our understanding of the resistive switching (RS) dynamics in the hybrid dielectric layer. Furthermore, the poor uniformity of key switching parameters remains a persistent issue in ReRAMs, which impedes any trends to be clearly defined through electrical characterization. This work uses electrical manipulation through a ramped-pulse series (RPS) method to improve the voltage and resistance fluctuations in the reset process of ultra-thin Al/Hf-hybrid/Ni devices. By analyzing their electrical behavior under different pulse and temperature conditions, we propose a comprehensive physical model that describes the operating mechanism of the device. Our results confirm the coexistence in the conductive filament (CF) of a hybrid metallic portion composed of Al and Hf3Al2 and an oxygen vacancy portion. The vacancies are found to play a significant role in RS, with most of them generated during the CF forming process and participating to different degrees in the filament rupture of the RPS-processed and non-RPS-processed devices via Joule heating, drift, and Fick forces. Additionally, we identify the cause of switching failure events to be based on the presence of an Al2O3 interlayer in the Al/Hf-hybrid interface.
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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