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Design, synthesis and characterization of linear unnatural amino acids for skin moisturization
Objectives
This work aimed to design, synthesize and characterize replacement natural moisturizing factor (NMF) composed of modified hygroscopic linear amino acids to pre-empt or repair skin barrier dysfunction.
Methods
Following synthesis and characterization, thermo-gravimetric analysis and quantum mechanics molecular modelling quantified and depicted water binding to the new compounds. Deliquescence relative humidity demonstrated the water-scavenging ability of the compounds, whereas snake skin moisturizing studies showed they increased water uptake into snake skin.
Results
From thermal analysis, N-hydroxyglycine showed greatest water-holding capacity followed by N-hydroxyserine, l-homoserine and α-hydroxyglycine; coupled with quantum mechanics molecular modelling, between 8 and 12 molecules of water could associate with each molecule of either N-hydroxyglycine, N-hydroxyserine or l-homoserine. All of our modified amino acids were efficacious and induced similar or greater water uptake compared with the established moisturizing compounds hyaluronic acid, glycerine and urea in snake skin. Incorporated at 10% in Oilatum, N-hydroxyserine induced >200% greater moisture uptake into dry snake skin compared to treatment with water alone, with efficacy related to the molecule structure and ability to bind to 12 water molecules. Oilatum cream spiked with all our unnatural amino acid hydrotropes increased water uptake into snake skin compared with Oilatum alone.
The compound series was designed to elucidate some structure – efficacy relationships. Amino acid chirality did not affect the water-holding capacity but did affect uptake into skin. Compounds with high melting points and bond energies tended to decrease water-holding capacity. With isosteric replacement, the more electronegative atoms gave greater water-holding capacities.
Conclusions
This work demonstrates the potential of unnatural amino acid hydrotropes as skin moisturizers and has developed some predictive ‘rules’ for further design and refinement of chemical structures
Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L
Purpose Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. Methods We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. Findings Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52–6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3–4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3–4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). Implications Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L
Magnetization relaxation in (Ga,Mn)As ferromagnetic semiconductors
We describe a theory of Mn local-moment magnetization relaxation due to p-d
kinetic-exchange coupling with the itinerant-spin subsystem in the
ferromagnetic semiconductor (Ga,Mn)As alloy. The theoretical Gilbert damping
coefficient implied by this mechanism is calculated as a function of Mn moment
density, hole concentration, and quasiparticle lifetime. Comparison with
experimental ferromagnetic resonance data suggests that in annealed strongly
metallic samples, p-d coupling contributes significantly to the damping rate of
the magnetization precession at low temperatures. By combining the theoretical
Gilbert coefficient with the values of the magnetic anisotropy energy, we
estimate that the typical critical current for spin-transfer magnetization
switching in all-semiconductor trilayer devices can be as low as .Comment: 4 pages, 2 figures, submitted to Rapid Communication
The T2K ND280 Off-Axis Pi-Zero Detector
The Pi-Zero detector (P{\O}D) is one of the subdetectors that makes up the
off-axis near detector for the Tokai-to-Kamioka (T2K) long baseline neutrino
experiment. The primary goal for the P{\O}D is to measure the relevant cross
sections for neutrino interactions that generate pi-zero's, especially the
cross section for neutral current pi-zero interactions, which are one of the
dominant sources of background to the electron neutrino appearance signal in
T2K. The P{\O}D is composed of layers of plastic scintillator alternating with
water bags and brass sheets or lead sheets and is one of the first detectors to
use Multi-Pixel Photon Counters (MPPCs) on a large scale.Comment: 17 pages, submitted to NIM
The T2K Side Muon Range Detector
The T2K experiment is a long baseline neutrino oscillation experiment aiming
to observe the appearance of {\nu} e in a {\nu}{\mu} beam. The {\nu}{\mu} beam
is produced at the Japan Proton Accelerator Research Complex (J-PARC), observed
with the 295 km distant Super- Kamiokande Detector and monitored by a suite of
near detectors at 280m from the proton target. The near detectors include a
magnetized off-axis detector (ND280) which measures the un-oscillated neutrino
flux and neutrino cross sections. The present paper describes the outermost
component of ND280 which is a side muon range detector (SMRD) composed of
scintillation counters with embedded wavelength shifting fibers and Multi-Pixel
Photon Counter read-out. The components, performance and response of the SMRD
are presented.Comment: 13 pages, 19 figures v2: fixed several typos; fixed reference
Nonperturbative renormalization group approach to frustrated magnets
This article is devoted to the study of the critical properties of classical
XY and Heisenberg frustrated magnets in three dimensions. We first analyze the
experimental and numerical situations. We show that the unusual behaviors
encountered in these systems, typically nonuniversal scaling, are hardly
compatible with the hypothesis of a second order phase transition. We then
review the various perturbative and early nonperturbative approaches used to
investigate these systems. We argue that none of them provides a completely
satisfactory description of the three-dimensional critical behavior. We then
recall the principles of the nonperturbative approach - the effective average
action method - that we have used to investigate the physics of frustrated
magnets. First, we recall the treatment of the unfrustrated - O(N) - case with
this method. This allows to introduce its technical aspects. Then, we show how
this method unables to clarify most of the problems encountered in the previous
theoretical descriptions of frustrated magnets. Firstly, we get an explanation
of the long-standing mismatch between different perturbative approaches which
consists in a nonperturbative mechanism of annihilation of fixed points between
two and three dimensions. Secondly, we get a coherent picture of the physics of
frustrated magnets in qualitative and (semi-) quantitative agreement with the
numerical and experimental results. The central feature that emerges from our
approach is the existence of scaling behaviors without fixed or pseudo-fixed
point and that relies on a slowing-down of the renormalization group flow in a
whole region in the coupling constants space. This phenomenon allows to explain
the occurence of generic weak first order behaviors and to understand the
absence of universality in the critical behavior of frustrated magnets.Comment: 58 pages, 15 PS figure
Low Q^2 Jet Production at HERA and Virtual Photon Structure
The transition between photoproduction and deep-inelastic scattering is
investigated in jet production at the HERA ep collider, using data collected by
the H1 experiment. Measurements of the differential inclusive jet
cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the
transverse energy and the pseudorapidity of the jets in the virtual
photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3
< y < 0.6. The interpretation of the results in terms of the structure of the
virtual photon is discussed. The data are best described by QCD calculations
which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure
Hadron Production in Diffractive Deep-Inelastic Scattering
Characteristics of hadron production in diffractive deep-inelastic
positron-proton scattering are studied using data collected in 1994 by the H1
experiment at HERA. The following distributions are measured in the
centre-of-mass frame of the photon dissociation system: the hadronic energy
flow, the Feynman-x (x_F) variable for charged particles, the squared
transverse momentum of charged particles (p_T^{*2}), and the mean p_T^{*2} as a
function of x_F. These distributions are compared with results in the gamma^* p
centre-of-mass frame from inclusive deep-inelastic scattering in the
fixed-target experiment EMC, and also with the predictions of several Monte
Carlo calculations. The data are consistent with a picture in which the
partonic structure of the diffractive exchange is dominated at low Q^2 by hard
gluons.Comment: 16 pages, 6 figures, submitted to Phys. Lett.
Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA
An investigation of the hadronic final state in diffractive and
non--diffractive deep--inelastic electron--proton scattering at HERA is
presented, where diffractive data are selected experimentally by demanding a
large gap in pseudo --rapidity around the proton remnant direction. The
transverse energy flow in the hadronic final state is evaluated using a set of
estimators which quantify topological properties. Using available Monte Carlo
QCD calculations, it is demonstrated that the final state in diffractive DIS
exhibits the features expected if the interaction is interpreted as the
scattering of an electron off a current quark with associated effects of
perturbative QCD. A model in which deep--inelastic diffraction is taken to be
the exchange of a pomeron with partonic structure is found to reproduce the
measurements well. Models for deep--inelastic scattering, in which a
sizeable diffractive contribution is present because of non--perturbative
effects in the production of the hadronic final state, reproduce the general
tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil
Measurement of D* Meson Cross Sections at HERA and Determination of the Gluon Density in the Proton using NLO QCD
With the H1 detector at the ep collider HERA, D* meson production cross
sections have been measured in deep inelastic scattering with four-momentum
transfers Q^2>2 GeV2 and in photoproduction at energies around W(gamma p)~ 88
GeV and 194 GeV. Next-to-Leading Order QCD calculations are found to describe
the differential cross sections within theoretical and experimental
uncertainties. Using these calculations, the NLO gluon momentum distribution in
the proton, x_g g(x_g), has been extracted in the momentum fraction range
7.5x10^{-4}< x_g <4x10^{-2} at average scales mu^2 =25 to 50 GeV2. The gluon
momentum fraction x_g has been obtained from the measured kinematics of the
scattered electron and the D* meson in the final state. The results compare
well with the gluon distribution obtained from the analysis of scaling
violations of the proton structure function F_2.Comment: 27 pages, 9 figures, 2 tables, submitted to Nucl. Phys.
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