7,934 research outputs found

    Sulfation-dependent recognition of high endothelial venules (HEV)-ligands by L-selectin and MECA 79, and adhesion-blocking monoclonal antibody.

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    L-selectin is a lectin-like receptor that mediates the attachment of lymphocytes to high endothelial venules (HEV) of lymph nodes during the process of lymphocyte recirculation. Two sulfated, mucin-like glycoproteins known as Sgp50/GlyCAM-1 and Sgp90/CD34 have previously been identified as HEV-associated ligands for L-selectin. These proteins were originally detected with an L-selectin/Ig chimera called LEC-IgG. GlyCAM-1 and CD34 are also recognized by an antiperipheral node addressin (PNAd) mAb called MECA 79, which blocks L-selectin-dependent adhesion and selectively stains lymph node HEV. The present study compares the requirements for the binding of MECA 79 and LEC-IgG to HEV-ligands. Whereas desialylation of GlyCAM-1 and CD34 drastically reduced binding to LEC-IgG, this treatment enhanced the binding of GlyCAM-1 to MECA 79. In contrast, the binding of both MECA 79 and LEC-IgG to GlyCAM-1 and CD34 was greatly decreased when the sulfation of these ligands was reduced with chlorate, a metabolic inhibitor of sulfation. Because MECA 79 stains HEV-like vessels at various sites of inflammation, recognition by L-selectin of ligands outside of secondary lymphoid organs may depend on sulfation. In addition to their reactivity with GlyCAM-1 and CD34, both MECA 79 and LEC-IgG recognize an independent molecule of approximately 200 kD in a sulfate-dependent manner. Thus, this molecule, which we designate Sgp200, is an additional ligand for L-selectin

    Just in time: Rosemary Butcher, making memories and marks

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    What is at stake in the relatively recent urge to document, annotate or archive decision-making processes in creative practices? Others have posed this sort of question (not least Derrida's Archive Fever, 1995), but, ironically enough, they tend to have done so through the written text—just as we are, in part, constrained to do here. Who or what has driven the historically specific urge to document—and who has benefited from it? Writer-researchers tend to be blissfully expert in the sorts of fields that collocate around performance decision-making—not least where university researcher holds sway. Yet surely what some of us may want—almost desperately—to capture, still evades that attempt at wording? What is it that holds centre-field, while researchers run around? Besides, what does the artist or maker really want? What do researchers want from ‘the artist’ when we use the words ’document’, ‘record’, ‘annotate’ and ‘archive’? When do we want it? Plainly Butcher has made the work, but ‘the work’, here, tends to signal the history of the made, rather less than the story of the making. In historical terms, most of Butcher's making processes pre-date this urge to document—except in her own mind, which bears their marks. What does Butcher remember? Perhaps her memories are the work's archive—hence, for whom do we archive, document and annotate, and how? In Derrida, concern was with time (in the beginning, in the end), and the command (do this! do that!), whereas what Butcher seems to recall is a series of questions, for which she continues to have few answers: the apparently simple ‘What was I doing then?’ signals an ongoing enquiry that image, writing and record fail to satisfy

    Just in time: ‘momentary’ events in the making of Rosemary Butcher’s signature practices

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    The notions of ‘ephemerality’, of time and loss, are essentially spectatorial, in the case of live performance. For the performance-maker, the work of making “the work”, over time, has never been ephemeral. Spectators’ performances and those of makers are non-identical, not least in terms of performances’ times. The ‘signature practices’ of the mature expert practitioner tend to emerge just in time, and the work is serial, a momentary instantiation in an ongoing creative enquiry, whereas spectating, in the event, mistakes its experience for “the work itself”. We propose to argue that times, the immutable and the immanent, engage with particular ways of seeing, so as to produce ‘signature practices’, in expert performance-making registers. The processes tend to be punctuated a ‘momentary instantiation’ (Knorr Cetina, 2001): the timely performance outcome that seems initially to end the enquiry, but that will reveal, to the practitioner concerned, a further set of questions to be worked through

    Thermodynamics and Kinetics of Ligand Photodissociation in Heme Proteins and Formation of DNA i-Motif

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    Heme proteins carry out a diverse array of functions in vivo while maintaining a well-conserved 3-over-3 α-helical structure. Human hemoglobin (Hb) is well-known for its oxygen transport function. Type 1 non-symbiotic hemoglobins (nsHb1) in plants and bacterial flavohemoglobins (fHb) from a variety of bacterial species have been predicted to carry out a nitric oxide dioxygenase function. In nsHb1 and fHb this function has been linked to protection from nitrosative stress. Herein, I combine photoacoustic calorimetry (PAC), transient absorption spectroscopy (TA), and classical molecular dynamics (cMD) simulations to characterize molecular mechanism of diatomic ligand interactions with a hexa-coordinate globin from plant (rice hemoglobin), bacterial flavohemoglobins and human hemoglobin. In rice type 1 non-symbiotic hemoglobin (rHb1), the dynamics and energetics of structural changes associated with ligand photodissociation is strongly impacted by solvent and temperature, namely CO escape from the protein matrix is slower at pH = 6.0 compare to neutral pH (ns) due to the CD loop reorganization which forms a pathway for ligand escape. In human hemoglobin, exogenous allosteric effectors modulate energetics of conformational changes associated with the CO and O2 escape although the effectors impact on rate constants for ligand association is small. The conformational dynamics associated with ligand photorelease from fHbs from Cupriavidus necator (FHP) and Staphylococcus aureus (HMPSa) are strongly modulated by the presence of azole drugs indicating that drug association modulates structural properties of the heme binding pocket. In addition, we carried out a study of the formation of the DNA intercalated motif (i-motif). The formation of the structure is strongly favored at acidic pH; therefore, PAC was combined with a 2-nitrobenzaldehyde pH-jump to probe formation of the i-motif on fast timescales. i-Motif folding is two-step process with the initial protonation of cytosine residues being endothermic with ΔHfast=8.5 ± 7.0 kcal mol-1 and ΔVfast=10.4 ± 1.6 mL mol-1 and subsequent nucleation/i-motif folding (τ = 140 ns) with ΔHslow=-51.5 ± 4.8 kcal mol-1 and ΔVslow=-6.6 ± 0.9 mL mol-1. The above results indicate that PAC can be employed to study diverse biochemical reactions such as DNA folding, drug binding and ligand photorelease from proteins

    ‘The voice is the guide to the experience as well as the experience itself’: An interview with non zero one

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Since 2009, non zero one – a London-based collective of artists with a background and interest in theatre but working across media and performance disciplines – has devised a series of unexpected, challenging but also light-hearted and inviting experiences of immersion. Whilst embracing a variety of techniques and contemporary media, one of the key features of the company’s work is the exploration of audience interaction through the use of headphones, typically in promenade and/or site-specific performance contexts. Following a first section that questions the role of voice in (theatrical) sonic immersion, the text unfolds as a dialogue between practitioner-scholar Konstantinos Thomaidis and non zero one artist and theatre director Sarah Butcher. The interview lends an attentive ear to the role of voice in the company’s work, from pre-recorded instruction to live audio interaction

    Using Wave-Packet Interferometry to Monitor the External Vibrational Control of Electronic Excitation Transfer

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    We investigate the control of electronic energy transfer in molecular dimers through the preparation of specific vibrational coherences prior to electronic excitation, and its observation by nonlinear wave-packet interferometry. Laser-driven coherent nuclear motion can affect the instantaneous resonance between site-excited electronic states and thereby influence short-time electronic excitation transfer (EET). We first illustrate this control mechanism with calculations on a dimer whose constituent monomers undergo harmonic vibrations. We then consider the use of nonlinear wave-packet interferometry (nl-WPI) experiments to monitor the nuclear dynamics accompanying EET in general dimer complexes following impulsive vibrational excitation by a sub-resonant control pulse (or control pulse sequence). In measurements of this kind, two pairs of polarized phase-related femtosecond pulses following the control pulse generate superpositions of coherent nuclear wave packets in optically accessible electronic states. Interference contributions to the time- and frequency-integrated fluorescence signal due to overlaps among the superposed wave packets provide amplitude-level information on the nuclear and electronic dynamics. We derive the basic expression for a control-pulse-dependent nl-WPI signal. The electronic transition moments of the constituent monomers are assumed to have a fixed relative orientation, while the overall orientation of the complex is distributed isotropically. We include the limiting case of coincident arrival by pulses within each phase-related pair in which control-influenced nl-WPI reduces to a fluorescence-detected pump-probe difference experiment. Numerical calculations of pump-probe signals based on these theoretical expressions are presented in the following paper

    The living aortic valve: From molecules to function.

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    The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70-90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve
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