2,803 research outputs found
AFM pulling and the folding of donor-acceptor oligorotaxanes: phenomenology and interpretation
The thermodynamic driving force in the self-assembly of the secondary
structure of a class of donor-acceptor oligorotaxanes is elucidated by means of
molecular dynamics simulations of equilibrium isometric single-molecule force
spectroscopy AFM experiments. The oligorotaxanes consist of
cyclobis(paraquat-\emph{p}-phenylene) rings threaded onto an oligomer of
1,5-dioxynaphthalenes linked by polyethers. The simulations are performed in a
high dielectric medium using MM3 as the force field. The resulting force vs.
extension isotherms show a mechanically unstable region in which the molecule
unfolds and, for selected extensions, blinks in the force measurements between
a high-force and a low-force regime. From the force vs. extension data the
molecular potential of mean force is reconstructed using the weighted histogram
analysis method and decomposed into energetic and entropic contributions. The
simulations indicate that the folding of the oligorotaxanes is energetically
favored but entropically penalized, with the energetic contributions overcoming
the entropy penalty and effectively driving the self-assembly. In addition, an
analogy between the single-molecule folding/unfolding events driven by the AFM
tip and the thermodynamic theory of first-order phase transitions is discussed
and general conditions, on the molecule and the cantilever, for the emergence
of mechanical instabilities and blinks in the force measurements in equilibrium
isometric pulling experiments are presented. In particular, it is shown that
the mechanical stability properties observed during the extension are
intimately related to the fluctuations in the force measurements.Comment: 42 pages, 17 figures, accepted to the Journal of Chemical Physic
Design of a fault tolerant airborne digital computer. Volume 2: Computational requirements and technology
This final report summarizes the work on the design of a fault tolerant digital computer for aircraft. Volume 2 is composed of two parts. Part 1 is concerned with the computational requirements associated with an advanced commercial aircraft. Part 2 reviews the technology that will be available for the implementation of the computer in the 1975-1985 period. With regard to the computation task 26 computations have been categorized according to computational load, memory requirements, criticality, permitted down-time, and the need to save data in order to effect a roll-back. The technology part stresses the impact of large scale integration (LSI) on the realization of logic and memory. Also considered was module interconnection possibilities so as to minimize fault propagation
Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation
AbstractCurrent antiretroviral therapy (ART) for HIV/AIDS slows disease progression by reducing viral loads and increasing CD4 counts. Yet ART is not curative due to the persistence of CD4+ T-cell proviral reservoirs that chronically resupply active virus. Elimination of these reservoirs through the administration of synergistic combinations of latency reversing agents (LRAs), such as histone deacetylase (HDAC) inhibitors and protein kinase C (PKC) modulators, provides a promising strategy to reduce if not eradicate the viral reservoir. Here, we demonstrate that largazole and its analogues are isoform-targeted histone deacetylase inhibitors and potent LRAs. Significantly, these isoform-targeted HDAC inhibitors synergize with PKC modulators, namely bryostatin-1 analogues (bryologs). Implementation of this unprecedented LRA combination induces HIV-1 reactivation to unparalleled levels and avoids global T-cell activation within resting CD4+ T-cells.</jats:p
Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing
Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but
limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi),
provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface
in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal
exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing
was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in
recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils
from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed
increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp
during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate
the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo
A rubric to assess opportunities for research engagement in the policy process.
Figure 1. A rubric to assess opportunities for research engagement in the policy process. Examples in the table are illustrative of possible modes of engagement. Source: Ratner, B & Dubois, M. et al 2022
Ion and polymer dynamics in polymer electrolytes PPO-LiClO4: II. 2H and 7Li NMR stimulated-echo experiment
We use 2H NMR stimulated-echo spectroscopy to measure two-time correlation
functions characterizing the polymer segmental motion in polymer electrolytes
PPO-LiClO4 near the glass transition temperature Tg. To investigate effects of
the salt on the polymer dynamics, we compare results for different ether oxygen
to lithium ratios, namely, 6:1, 15:1, 30:1 and infinity. For all compositions,
we find nonexponential correlation functions, which can be described by a
Kohlrausch function. The mean correlation times show quantitatively that an
increase of the salt concentration results in a strong slowing down of the
segmental motion. Consistently, for the high 6:1 salt concentration, a high
apparent activation energy E_a=4.1eV characterizes the temperature dependence
of the mean correlation times at Tg < T< 1.1T_g, while smaller values E_a=2.5eV
are observed for moderate salt contents. The correlation functions are most
nonexponential for 15:1 PPO-LiClO4, whereas the stretching is reduced for
higher and lower salt concentrations. A similar dependence of the correlation
functions on the evolution time in the presence and in the absence of ions
indicates that addition of salt hardly affects the reorientational mechanism.
For all compositions, mean jump angles of about 15 degree characterize the
segmental reorientation. In addition, comparison of results from 2H and 7Li NMR
stimulated-echo experiments suggests a coupling of ion and polymer dynamics in
15:1 PPO-LiClO4.Comment: 14 pages, 12 figure
Inelastic Proton‐Proton Scattering at Very High Energy
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87855/2/99_1.pd
Effects Of Length, Complexity, And Grammatical Correctness On Stuttering In Spanish-Speaking Preschool Children
Purpose: To explore the effects of utterance length, syntactic complexity, and grammatical correctness on stuttering in the spontaneous speech of young, monolingual Spanish-speaking children. Method: Spontaneous speech samples of 11 monolingual Spanish-speaking children who stuttered, ages 35 to 70 months, were examined. Mean number of syllables, total number of clauses, utterance complexity (i.e., containing no clauses, simple clauses, or subordinate and/or conjoined clauses), and grammatical correctness (i.e., the presence or absence of morphological and syntactical errors) in stuttered and fluent utterances were compared. Results: Findings revealed that stuttered utterances in Spanish tended to be longer and more often grammatically incorrect, and contain more clauses, including more subordinate and/or conjoined clauses. However, when controlling for the interrelatedness of syllable number and clause number and complexity, only utterance length and grammatical incorrectness were significant predictors of stuttering in the spontaneous speech of these Spanish-speaking children. Use of complex utterances did not appear to contribute to the prediction of stuttering when controlling for utterance length. Conclusions: Results from the present study were consistent with many earlier reports of English-speaking children. Both length and grammatical factors appear to affect stuttering in Spanish-speaking children. Grammatical errors, however, served as the greatest predictor of stuttering.Communication Sciences and Disorder
Immobilization of Polyethylene Oxide Surfactants for Non-Fouling Biomaterial Surfaces Using an Argon Glow Discharge Treatment
A non-fouling (protein-resistant) polymer surface is achieved by the covalent immobilization of polyethylene oxide (PEO) surfactants using an inert gas discharge treatment. Treated surfaces have been characterized using electron spectroscopy for chemical analysis (ESCA), static secondary ion mass spectrometry (SSIMS), water contact angle measurement, fibrinogen adsorption, and platelet adhesion. This paper is intended to review our recent work in using this simple surface modification process to obtain wettable polymer surfaces in general, and non-fouling biomaterial surfaces in particular
The Formal Dynamism of Categories: Stops vs. Fricatives, Primitivity vs. Simplicity
Minimalist Phonology (MP; Pöchtrager 2006) constructs its theory based on the phonological epistemological principle (Kaye 2001) and exposes the arbitrary nature of standard Government Phonology (sGP) and strict-CV (sCV), particularly with reference to their confusion of melody and structure.
For Pöchtrager, these are crucially different, concluding that place of articulation is melodic (expressed with elements), while manner of articulation is structural. In this model, the heads (xN and xO) can license and incorporate the length of the other into their own interpretation, that is xN influences xO projections as well as its own and vice versa. This dynamism is an aspect of the whole framework and this paper in particular will show that stops and fricatives evidence a plasticity of category and that, although fricatives are simpler in structure, stops are the more primitive of the two.
This will be achieved phonologically through simply unifying the environment of application of the licensing forces within Pöchtrager's otherwise sound onset structure. In doing so, we automatically make several predictions about language acquisition and typology and show how lenition in Qiang (Sino-Tibetan) can be more elegantly explained
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