626 research outputs found
Axial and Vector Correlator Mixing in Hot and Dense Hadronic Matter
We study the manifestations of chiral symmetry restoration which have a
significance for the parity mixing. Restricting to pions and nucleons we
establish a formalism for the expression of the vector correlator, which
displays the mixing of the axial correlator into the vector one and unifies the
cases of the heat bath and the dense medium. We give examples of mixing
cross-sections. We also establish a link between the energy integrated mixing
cross-sections and the pion scalar density which governs the quenching factors
of coupling constants, such as the pion decay one, as well as the quark
condensate evolution.Comment: 12 pages, Latex, 4 PostScript Figure
An Olfactory Receptor Pseudogene whose Function emerged in Humans
Human olfactory receptor, hOR17-210, is identified as a pseudogene in the human genome. Experimental data has shown however, that the gene product of cloned hOR17-210 cDNA was able to bind an odorant-binding protein and is narrowly tuned for excitation by cyclic ketones. Supported by experimental results, we used the bioinformatics methods of sequence analysis, computational protein modeling and docking, to show that functionality in this receptor is retained due to sequence-structure features not previously observed in mammalian ORs. This receptor does not possess the first two transmembrane helical domains (of seven typically seen in GPCRs). It however, possesses an additional TM that has not been observed in other human olfactory receptors. By incorporating these novel structural features, we created two putative models for this receptor. We also docked odor ligands that were experimentally shown to bind hOR17-210 model. We show how and why structural modifications of OR17-210 do not hinder this receptor's functionality. Our studies reveal that novel gene rearrangement that result in sequence and structural diversity in has a bearing on OR and GPCR function and evolution
Interactions of cholera toxin with isolated hepatocytes. Effects of low pH, chloroquine and monensin on toxin internalization, processing and action
A phase I pharmacokinetic and safety study of cabazitaxel in adult cancer patients with normal and impaired renal function
Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function.
Cohorts A (normal renal function: creatinine clearance [CrCL]Â >80Â mL/min/1.73Â m), B (moderate renal impairment: CrCL 30 to <50Â mL/min/1.73Â m) and C (severe impairment: CrCLÂ <30Â mL/min/1.73Â m(2)) received cabazitaxel 25Â mg/m (A, B) or 20Â mg/m(2) (C, could be escalated to 25Â mg/m), once every 3Â weeks. Pharmacokinetic parameters and cabazitaxel unbound fraction (F) were assessed using linear regression and mixed models. Geometric mean (GM) and GM ratios (GMRs) were determined using mean CrCL intervals (moderate and severe renal impairment: 40 and 15Â mL/min/1.73Â m) versus a control (90Â mL/min/1.73Â m).
Overall, 25 patients received cabazitaxel (median cycles: 3 [range 1-20]; Cohort A: 5 [2-13]; Cohort B: 3 [1-15]; and Cohort C: 5 [1-20]), of which 24 were eligible for pharmacokinetic analysis (eight in each cohort). For moderate and severe renal impairment versus normal renal function, GMR estimates were: clearance normalized to body surface area (CL/BSA) 0.95 (90% CI 0.80-1.13) and 0.89 (0.61-1.32); area under the curve normalized to dose (AUC/dose) 1.06 (0.88-1.27) and 1.14 (0.76-1.71); and F U 0.99 (0.94-1.04) and 0.97 (0.87-1.09), respectively. Estimated slopes of linear regression of log parameters versus log CrCL (renal impairment) were: CL/BSA 0.06 (-0.15 to 0.28); AUC/dose -0.07 (-0.30 to 0.16); and F U 0.02 (-0.05 to 0.08). Cabazitaxel safety profile was consistent with previous reports.
Renal impairment had no clinically meaningful effect on cabazitaxel pharmacokinetics.This study was supported by Sanofi. Javier Garcia-Corbacho acknowledges clinical fellowship support from SEOM. Experimental Cancer Medicine Centre (ECMC) and NIHR Biomedical Research Centre (BRC) funding is also acknowledged for the Cambridge Cancer Centre
Pharmacokinetic (Pk) Activity of Cabazitaxel (Cbz) in Patients (Pts) with Renal Impairment (Ri)
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Meson-induced correlations of nucleons in nuclear Compton scattering
The non-resonant (seagull) contribution to the nuclear Compton amplitude at
low energies is strongly influenced by nucleon correlations arising from meson
exchange. We study this problem in a modified Fermi gas model, where nuclear
correlation functions are obtained with the help of perturbation theory. The
dependence of the mesonic seagull amplitude on the nuclear radius is
investigated and the influence of a realistic nuclear density on this amplitude
is dicussed. We found that different form factors appear for the static part
(proportional to the enhancement constant ) of the mesonic seagull
amplitude and for the parts, which contain the contribution from
electromagnetic polarizabilities.Comment: 15 pages, Latex, epsf.sty, 9 eps figures
Articulating practice through the interview to the double
The paper aims to realise the critical potential of the practice lens by contributing to the
development of a coherent set of methodologies for investigating work and
organisational activity. It does so by introducing and critically assessing the "interview
to the double" as a method to articulate and represent practice.
After briefly illustrating its history and usage, the paper analyses in depth the setting
generated by this unusual interview method. It argues that the nature of the encounter
produces narratives that are often morally connoted and idealised in character. As a
consequence the method is especially useful to capture the going concerns which orient
the conduct of the members and the normative and moral dimension of practice. The
paper also shows that because it mimics familiar instruction-giving discursive practices,
the method constitutes an effective textual device to convey this moral and normative
dimension in a way which remains faithful to its situated and contingent nature of
practice
Electromagnetic Polarizabilities of Nucleons bound in Ca, O and He
Differential cross sections for elastic scattering of photons have been
measured for Ca at energies of 58 and 74 MeV and for O and He
at 61 MeV, in the angular range from 45 to 150. Evidence is obtained
that there are no significant in-medium modifications of the electromagnetic
polarizabilities except for those originating from meson exchange currents.Comment: 20 pages including 5 Figure
Analysis of current perioperative management with HaemateÂź P/Humate PÂź in von Willebrand disease
Introduction: Patients with Von Willebrand disease (VWD) are regularly treated with VWF-containing concentrates in case of acute bleeding, trauma and dental or surgical procedures.
Aim: In this multicentre retrospective study, current perioperative management with a von Willebrand factor (VWF)/Factor VIII (FVIII) concentrate (HaemateÂź P) in patients with VWD was evaluated. Patients/Methods: Patients with VWD undergoing minor or major surgery between 2000 and 2015, requiring treatment with a VWF/FVIII concentrate (HaemateÂź P), were included. Achieved VWF activity (VWF:Act) and FVIII during FVIII-based treatment regimens were compared to predefined target levels in national guidelines.
Results: In total, 103 patients with VWD (148 surgeries) were included: 54 type 1 (73 surgeries), 43 type 2 (67 surgeries) and 6 type 3 (8 surgeries). Overall, treatment resulted in high VWF:Act and FVIII levels, defined as â„0.20 IU/mL above predefined levels. In patients with type 1 VWD, respectively, 65% and 91% of trough VWF:Act and FVIII levels were higher than target levels. In patients with type 2 and type 3 VWD, respectively, 53% and 57% of trough VWF:Act and 72% and 73% of trough FVIII levels were higher than target level. Furthermore, FVIII accumulation over time was observed, while VWF:Act showed a declining trend, leading to significantly higher levels of FVIII than VWF:Act.
Conclusion: High VWF:Act and accumulation of FVIII were observed after perioperative FVIII-based replacement therapy in patients with VWD, both underlining the necessity of personalization of dosing regimens to optimize perioperative treatment
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