2,602 research outputs found
Emergence of highly-ordered hierarchical nanoscale aggregates on electrostatic binding of self-assembled multivalent (SAMul) cationic micelles with polyanionic heparin
We report three surfactants, with cationic N,N-di-(3-aminopropyl)-N-methylamine (DAPMA) head groups and aliphatic chains connected via an amide linkage, and investigate their ability to self-assemble and bind polyanionic heparin – a process of potential clinical importance in coagulation control. Modifying the hydrophobic chain length tunes the self-assembly event, with C16-DAPMA having the lowest critical micelle concentration and also being the optimal heparin binder. Remarkably highly structured hierarchical nanoscale aggregates are formed on binding between the spherical cationic micelles and linear polyanionic heparin. C14-DAPMA and C16-DAPMA yield organized polycrystalline assemblies as observed by transmission electron microscopy (TEM), predicted in solution by mesoscale simulations and characterized by small-angle X-ray scattering (SAXS). This confirms that the micelles remain intact during the hierarchical assembly process and become packed in a face-centered cubic manner. The nanoscale assembly formed by C16-DAPMA showed the highest degree of order. Importantly, these studies indicate the impact of hydrophobic modification on self-assembly and heparin binding, demonstrate remarkably high stability of these self-assembled micelles even when forming strong electrostatic interactions with heparin, and provide structural insights into nanoscale hierarchical electrostatic assemblies
Light driven water oxidation by a single site cobalt salophen catalyst
A salophen cobalt(II) complex enables water oxidation at neutral pH
in photoactivated sacrificial cycles under visible light, thus confirming
the high appeal of earth abundant single site catalysis for artificial
photosynthesis
An Integrated Pharmacological Counselling Approach to Guide Decision-Making in the Treatment with CDK4/6 Inhibitors for Metastatic Breast Cancer
A wide inter-individual variability in the therapeutic response to cyclin-dependent kinases 4 and 6 inhibitors (CDKis) has been reported. We herein present a case series of five patients treated with either palbociclib or ribociclib referred to our clinical pharmacological counselling, including therapeutic drug monitoring (TDM), pharmacogenetics, and drug–drug interaction analysis to support clinicians in the management of CDKis treatment for metastatic breast cancer. Patients’ plasma samples for TDM analysis were collected at steady state and analyzed by an LC-MS/MS method for minimum plasma concentration (Cmin) evaluation. Under and overexposure to the drug were defined based on the mean Cmin values observed in population pharmacokinetic studies. Polymorphisms in selected genes encoding for proteins involved in drug absorption, distribution, metabolism, and elimination were analyzed (CYP3A4, CYP3A5, ABCB1, SLCO1B1, and ABCG2). Three of the five reported cases presented a CDKi plasma level above the population mean value and were referred for toxicity. One of them presented a low function ABCB1 haplotype (ABCB1-rs1128503, rs1045642, and rs2032582), possibly causative of both increased drug oral absorption and plasmatic concentration. Two patients showed underexposure to CDKis, and one of them was referred for early progression. In one patient, a CYP3A5*1/*3 genotype was found to be potentially responsible for more efficient drug metabolism and lower drug plasma concentration. This intensified pharmacological approach in clinical practice has been shown to be potentially effective in supporting prescribing oncologists with dose and drug selection and could be ultimately useful for increasing both the safety and efficacy profiles of CDKi treatment
CYP2D6 and CYP2C8 pharmacogenetics and pharmacological interactions to predict imatinib plasmatic exposure in GIST patients
Patients on treatment with oral fixed dose imatinib are frequently under- or overexposed to the drug. We investigated the association between the gene activity score (GAS) of imatinib-metabolizing cytochromes (CYP3A4, CYP3A5, CYP2D6, CYP2C9, CYP2C19, CYP2C8) and imatinib and nor-imatinib exposure. We also investigated the impact of concurrent drug-drug-interactions (DDIs) on the association between GAS and imatinib exposure
Measurement of event shapes in deep inelastic scattering at HERA
Inclusive event-shape variables have been measured in the current region of
the Breit frame for neutral current deep inelastic ep scattering using an
integrated luminosity of 45.0 pb^-1 collected with the ZEUS detector at HERA.
The variables studied included thrust, jet broadening and invariant jet mass.
The kinematic range covered was 10 < Q^2 < 20,480 GeV^2 and 6.10^-4 < x < 0.6,
where Q^2 is the virtuality of the exchanged boson and x is the Bjorken
variable. The Q dependence of the shape variables has been used in conjunction
with NLO perturbative calculations and the Dokshitzer-Webber non-perturbative
corrections (`power corrections') to investigate the validity of this approach.Comment: 7+25 pages, 6 figure
Dissociation of virtual photons in events with a leading proton at HERA
The ZEUS detector has been used to study dissociation of virtual photons in
events with a leading proton, gamma^* p -> X p, in e^+p collisions at HERA. The
data cover photon virtualities in two ranges, 0.03<Q^2<0.60 GeV^2 and 2<Q^2<100
GeV^2, with M_X>1.5 GeV, where M_X is the mass of the hadronic final state, X.
Events were required to have a leading proton, detected in the ZEUS leading
proton spectrometer, carrying at least 90% of the incoming proton energy. The
cross section is presented as a function of t, the squared four-momentum
transfer at the proton vertex, Phi, the azimuthal angle between the positron
scattering plane and the proton scattering plane, and Q^2. The data are
presented in terms of the diffractive structure function, F_2^D(3). A
next-to-leading-order QCD fit to the higher-Q^2 data set and to previously
published diffractive charm production data is presented
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Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays
The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange
hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6
e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at
the PEP-II collider. The spectrum is used to measure the branching fraction B(B
--> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the
first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm
0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm
0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011
\pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the
photon energy in the B-meson rest frame. Results are also presented for
narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B -->
X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also
unfolded to the B-meson rest frame; that is the frame in which theoretical
predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No
analysis or results have changed from previous version. Some changes to
improve clarity based on interactions with Phys. Rev. D referees, including
one new Figure (Fig. 13), and some minor wording/punctuation/spelling
mistakes fixe
Search for lepton-flavor violation at HERA
A search for lepton-flavor-violating interactions and has been performed with the ZEUS detector using the entire HERA I
data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data
were taken at center-of-mass energies, , of 300 and 318 GeV. No
evidence of lepton-flavor violation was found, and constraints were derived on
leptoquarks (LQs) that could mediate such interactions. For LQ masses below
, limits were set on , where
is the coupling of the LQ to an electron and a
first-generation quark , and is the branching ratio of
the LQ to the final-state lepton ( or ) and a quark . For
LQ masses much larger than , limits were set on the four-fermion
interaction term for LQs that couple to an electron and a quark
and to a lepton and a quark , where and are
quark generation indices. Some of the limits are also applicable to
lepton-flavor-violating processes mediated by squarks in -Parity-violating
supersymmetric models. In some cases, especially when a higher-generation quark
is involved and for the process , the ZEUS limits are the most
stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig.
6) adde
The dependence of dijet production on photon virtuality in ep collisions at HERA
The dependence of dijet production on the virtuality of the exchanged photon,
Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 <
2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of
38.6 pb^-1.
Dijet cross sections were measured for jets with transverse energy E_T^jet >
7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame
in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon
momentum entering the hard process, was used to enhance the sensitivity of the
measurement to the photon structure. The Q^2 dependence of the ratio of low- to
high-xg^obs events was measured.
Next-to-leading-order QCD predictions were found to generally underestimate
the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models
based on leading-logarithmic parton-showers, using a partonic structure for the
photon which falls smoothly with increasing Q^2, provide a qualitative
description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.
Beauty photoproduction measured using decays into muons in dijet events in ep collisions at =318 GeV
The photoproduction of beauty quarks in events with two jets and a muon has
been measured with the ZEUS detector at HERA using an integrated luminosity of
110 pb. The fraction of jets containing b quarks was extracted from the
transverse momentum distribution of the muon relative to the closest jet.
Differential cross sections for beauty production as a function of the
transverse momentum and pseudorapidity of the muon, of the associated jet and
of , the fraction of the photon's momentum participating in
the hard process, are compared with MC models and QCD predictions made at
next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September
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