7,345 research outputs found
Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin
A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures.
Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted
Analytic Representations of Yang-Mills Amplitudes
Scattering amplitudes in Yang-Mills theory can be represented in the
formalism of Cachazo, He and Yuan (CHY) as integrals over an auxiliary
projective space---fully localized on the support of the scattering equations.
Because solving the scattering equations is difficult and summing over the
solutions algebraically complex, a method of directly integrating the terms
that appear in this representation has long been sought. We solve this
important open problem by first rewriting the terms in a manifestly
Mobius-invariant form and then using monodromy relations (inspired by analogy
to string theory) to decompose terms into those for which combinatorial rules
of integration are known. The result is a systematic procedure to obtain
analytic, covariant forms of Yang-Mills tree-amplitudes for any number of
external legs and in any number of dimensions. As examples, we provide compact
analytic expressions for amplitudes involving up to six gluons of arbitrary
helicities.Comment: 29 pages, 43 figures; also included is a Mathematica notebook with
explicit formulae. v2: citations added, and several (important) typos fixe
Proving the Turing Universality of Oritatami Co-Transcriptional Folding (Full Text)
We study the oritatami model for molecular co-transcriptional folding. In
oritatami systems, the transcript (the "molecule") folds as it is synthesized
(transcribed), according to a local energy optimisation process, which is
similar to how actual biomolecules such as RNA fold into complex shapes and
functions as they are transcribed. We prove that there is an oritatami system
embedding universal computation in the folding process itself.
Our result relies on the development of a generic toolbox, which is easily
reusable for future work to design complex functions in oritatami systems. We
develop "low-level" tools that allow to easily spread apart the encoding of
different "functions" in the transcript, even if they are required to be
applied at the same geometrical location in the folding. We build upon these
low-level tools, a programming framework with increasing levels of abstraction,
from encoding of instructions into the transcript to logical analysis. This
framework is similar to the hardware-to-algorithm levels of abstractions in
standard algorithm theory. These various levels of abstractions allow to
separate the proof of correctness of the global behavior of our system, from
the proof of correctness of its implementation. Thanks to this framework, we
were able to computerize the proof of correctness of its implementation and
produce certificates, in the form of a relatively small number of proof trees,
compact and easily readable and checkable by human, while encapsulating huge
case enumerations. We believe this particular type of certificates can be
generalized to other discrete dynamical systems, where proofs involve large
case enumerations as well
Properties of the Scale Invariant Lipatov Kernel
We study the scale-invariant kernel which appears as an infra-red
contribution in the BFKL evolution equation and is constructed via
multiparticle -channel unitarity. We detail the variety of Ward identity
constraints and infra-red cancellations that characterize its infrared
behaviour. We give an analytic form for the full non-forward kernel. For the
forward kernel controlling parton evolution at small-x, we give an impact
parameter representation, derive the eigenvalue spectrum, and demonstrate a
holomorphic factorisation property related to conformal invariance. The results
show that, at next-to-leading-order, the transverse momentum infra-red region
may produce a strong reduction of the BFKL small-x behavior.Comment: 41 pages in latex, 16 figs. in a uu-encoded ps-fil
Distinguishing between SU(5) and flipped SU(5)
We study in detail the d=6 operators for proton decay in the two possible
matter unification scenarios based on SU(5) gauge symmetry. We investigate the
way to distinguish between these two scenarios. The dependence of the branching
ratios for the two body decays on the fermion mixing is presented in both
cases. We point out the possibility to make a clear test of flipped SU(5)
through the decay channel p \to \pi^+ \bar{\nu}, and the ratio \tau(p \to K^0
e^+_{\alpha}) / \tau(p \to \pi^0 e^+_{\alpha}).Comment: 10 pages, minor correction
Magnetometry with nitrogen-vacancy ensembles in diamond based on infrared absorption in a doubly resonant optical cavity
We propose to use an optical cavity to enhance the sensitivity of
magnetometers relying on the detection of the spin state of high-density
nitrogen-vacancy ensembles in diamond using infrared optical absorption. The
role of the cavity is to obtain a contrast in the absorption-detected magnetic
resonance approaching unity at room temperature. We project an increase in the
photon shot-noise limited sensitivity of two orders of magnitude in comparison
with a single-pass approach. Optical losses can limit the enhancement to one
order of magnitude which could still enable room temperature operation.
Finally, the optical cavity also allows to use smaller pumping power when it is
designed to be resonant at both the pump and the signal wavelength
Structural analysis of the adenovirus type 2 E3/19K protein using mutagenesis and a panel of conformation-sensitive monoclonal antibodies
The E3/19K protein of human adenovirus type 2 (Ad2) was the first viral protein shown to interfere with antigen presentation. This 25 kDa transmembrane glycoprotein binds to major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER), thereby preventing transport of newly synthesized peptide–MHC complexes to the cell surface and consequently T cell recognition. Recent data suggest that E3/19K also sequesters MHC class I like ligands intracellularly to suppress natural killer (NK) cell recognition. While the mechanism of ER retention is well understood, the structure of E3/19K remains elusive. To further dissect the structural and antigenic topography of E3/19K we carried out site-directed mutagenesis and raised monoclonal antibodies (mAbs) against a recombinant version of Ad2 E3/19K comprising the lumenal domain followed by a C-terminal histidine tag. Using peptide scanning, the epitopes of three mAbs were mapped to different regions of the lumenal domain, comprising amino acids 3–13, 15–21 and 41–45, respectively. Interestingly, mAb 3F4 reacted only weakly with wild-type E3/19K, but showed drastically increased binding to mutant E3/19K molecules, e.g. those with disrupted disulfide bonds, suggesting that 3F4 can sense unfolding of the protein. MAb 10A2 binds to an epitope apparently buried within E3/19K while that of 3A9 is exposed. Secondary structure prediction suggests that the lumenal domain contains six β-strands and an α-helix adjacent to the transmembrane domain. Interestingly, all mAbs bind to non-structured loops. Using a large panel of E3/19K mutants the structural alterations of the mutations were determined. With this knowledge the panel of mAbs will be valuable tools to further dissect structure/function relationships of E3/19K regarding down regulation of MHC class I and MHC class I like molecules and its effect on both T cell and NK cell recognition
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