66 research outputs found
Time-domain Brillouin Scattering as a Local Temperature Probe in Liquids
We present results of time-domain Brillouin scattering (TDBS) to determine
the local temperature of liquids in contact to an optical transducer. TDBS is
based on an ultrafast pump-probe technique to determine the light scattering
frequency shift caused by the propagation of coherent acoustic waves in a
sample. Since the temperature influences the Brillouin scattering frequency
shift, the TDBS signal probes the local temperature of the liquid. Results for
the extracted Brillouin scattering frequencies recorded at different liquid
temperatures and at different laser powers - i.e. different steady state
background temperatures- are shown to demonstrate the usefulness of TDBS as a
temperature probe. This TDBS experimental scheme is a first step towards the
investigation of ultrathin liquids measured by GHz ultrasonic probing.Comment: arXiv admin note: substantial text overlap with arXiv:1702.0107
Evaluating QBF Solvers: Quantifier Alternations Matter
We present an experimental study of the effects of quantifier alternations on
the evaluation of quantified Boolean formula (QBF) solvers. The number of
quantifier alternations in a QBF in prenex conjunctive normal form (PCNF) is
directly related to the theoretical hardness of the respective QBF
satisfiability problem in the polynomial hierarchy. We show empirically that
the performance of solvers based on different solving paradigms substantially
varies depending on the numbers of alternations in PCNFs. In related
theoretical work, quantifier alternations have become the focus of
understanding the strengths and weaknesses of various QBF proof systems
implemented in solvers. Our results motivate the development of methods to
evaluate orthogonal solving paradigms by taking quantifier alternations into
account. This is necessary to showcase the broad range of existing QBF solving
paradigms for practical QBF applications. Moreover, we highlight the potential
of combining different approaches and QBF proof systems in solvers.Comment: preprint of a paper to be published at CP 2018, LNCS, Springer,
including appendi
The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria
The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria
Corticosteroid Binding Globulin Structural Basis for Steroid Transport and Proteinase Triggered Release
Corticosteroid binding globulin CBG is a serine proteinase inhibitor serpin family member that transports glucocorticoids in blood and regulates their access to target cells. The 1.9 crystal structure of rat CBG shows that its steroid binding site resembles the thyroxin binding site in the related serpin, thyroxin binding globulin, and mutagenesis studies have confirmed the contributions of key residues that constitute the steroid binding pocket. Unlike thyroxin bound thyroxin binding globulin, the cortisol bound CBG displays an active serpin conformation with the proteinase sensitive, reactive center loop RCL fully expelled from the regulatory amp; 946; sheet A. Moreover, the CBG structure allows us to predict that complete insertion of the proteolytically cleaved RCL into the serpin fold occurs in concert with a displacement and unwinding of helix D that would disrupt the steroid binding site. This allosteric coupling between RCL positioning and occupancy of the CBG steroid binding site, which resembles the ligand glycosamino glycan dependent activation of the thrombin inhibitory serpins heparin cofactor II and anti thrombin RCLs, ensures both optimal recognition of CBG by target proteinases and efficient release of steroid to sites of actio
Copyright Notice
This document describes the congestion management system of Comcast Cable, a large cable broadband Internet Service Provider (ISP) in the U.S. Comcast completed deployment of this congestion management system on December 31, 2008. Status of This Memo This document is not an Internet Standards Track specification; it is published for informational purposes. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Not all documents approved by the IESG are a candidate for any level of Internet Standard; see Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained a
- …