3,356 research outputs found
Residue analysis of tetracyclines in poultry muscle: Shortcomings revealed by a proficiency test
Magnetic friction due to vortex fluctuation
We use Monte Carlo and molecular dynamics simulation to study a magnetic
tip-sample interaction. Our interest is to understand the mechanism of heat
dissipation when the forces involved in the system are magnetic in essence. We
consider a magnetic crystalline substrate composed of several layers
interacting magnetically with a tip. The set is put thermally in equilibrium at
temperature T by using a numerical Monte Carlo technique. By using that
configuration we study its dynamical evolution by integrating numerically the
equations of motion. Our results suggests that the heat dissipation in this
system is closed related to the appearing of vortices in the sample.Comment: 6 pages, 41 figure
Long range molecular dynamics study of regulation of eukaryotic glucosamine-6-phosphate synthase activity by UDP-GlcNAc
Glucosamine-6-phosphate (GlcN-6-P) synthase catalyses the first and practically irreversible step in hexosamine metabolism. The final product of this pathway, uridine 5’ diphospho N-acetyl-D-glucosamine (UDP-GlcNAc), is an essential substrate for assembly of bacterial and fungal cell walls. Moreover, the enzyme is involved in phenomenon of hexosamine induced insulin resistance in type II diabetes, which makes it a potential target for antifungal, antibacterial and antidiabetic therapy. The crystal structure of the isomerase domain of GlcN-6-P synthase from human pathogenic fungus Candida albicans, in complex with UDP-GlcNAc has been solved recently but it has not revealed the molecular mechanism of inhibition taking place under UDP-GlcNAc influence, the unique feature of the eukaryotic enzyme. UDP-GlcNAc is a physiological inhibitor of GlcN-6-P synthase, binding about 1 nm away from the active site of the enzyme. In the present work, comparative molecular dynamics simulations of the free and UDP-GlcNAc-bounded structures of GlcN-6-P synthase have been performed. The aim was to complete static X-ray structural data and detect possible changes in the dynamics of the two structures. Results of the simulation studies demonstrated higher mobility of the free structure when compared to the liganded one. Several amino acid residues were identified, flexibility of which is strongly affected upon UDP-GlcNAc binding. Importantly, the most fixed residues are those related to the inhibitor binding process and to the catalytic reaction. The obtained results constitute an important step toward understanding of mechanism of GlcN-6-P synthase inhibition by UDP-GlcNAc molecule
High frequency longitudinal and transverse dynamics in water
High-resolution, inelastic x-ray scattering measurements of the dynamic
structure factor S(Q,\omega) of liquid water have been performed for wave
vectors Q between 4 and 30 nm^-1 in distinctly different thermodynamic
conditions (T= 263 - 420 K ; at, or close to, ambient pressure and at P = 2
kbar). In agreement with previous inelastic x-ray and neutron studies, the
presence of two inelastic contributions (one dispersing with Q and the other
almost non-dispersive) is confirmed. The study of their temperature- and
Q-dependence provides strong support for a dynamics of liquid water controlled
by the structural relaxation process. A viscoelastic analysis of the
Q-dispersing mode, associated with the longitudinal dynamics, reveals that the
sound velocity undergoes the complete transition from the adiabatic sound
velocity (c_0) (viscous limit) to the infinite frequency sound velocity
(c_\infinity) (elastic limit). On decreasing Q, as the transition regime is
approached from the elastic side, we observe a decrease of the intensity of the
second, weakly dispersing feature, which completely disappears when the viscous
regime is reached. These findings unambiguously identify the second excitation
to be a signature of the transverse dynamics with a longitudinal symmetry
component, which becomes visible in the S(Q,\omega) as soon as the purely
viscous regime is left.Comment: 28 pages, 12 figure
Amorphous carbon nanoparticles: a versatile label for rapid diagnostic (immuno)assays
Carbon nanoparticles (CNPs) labeled with reporter molecules can serve as signaling labels in rapid diagnostic assays as an alternative to gold, colored latex, silica, quantum dots, or up-converting phosphor nanoparticles. Detailed here is the preparation of biomolecule-labeled CNPs and examples of their use as a versatile label. CNPs can be loaded with a range of biomolecules, such as DNA, antibodies, and proteins (e.g., neutravidin or a fusion protein of neutravidin with an enzyme), and the resulting conjugates can be used to detect analytes of high or low molecular mass
Supercooled confined water and the Mode Coupling crossover temperature
We present a Molecular Dynamics study of the single particle dynamics of
supercooled water confined in a silica pore. Two dynamical regimes are found:
close to the hydrophilic substrate molecules are below the Mode Coupling
crossover temperature, , already at ambient temperature. The water closer
to the center of the pore (free water) approaches upon supercooling as
predicted by Mode Coupling Theories. For free water the crossover temperature
and crossover exponent are extracted from power-law fits to both the
diffusion coefficient and the relaxation time of the late region.Comment: To be published, Phys. Rev. Lett., 4 pages, 3 figures, revTeX, minor
changes in the figures, references added, changes in the tex
Molecular dynamics simulation of polymer helix formation using rigid-link methods
Molecular dynamics simulations are used to study structure formation in
simple model polymer chains that are subject to excluded volume and torsional
interactions. The changing conformations exhibited by chains of different
lengths under gradual cooling are followed until each reaches a state from
which no further change is possible. The interactions are chosen so that the
true ground state is a helix, and a high proportion of simulation runs succeed
in reaching this state; the fraction that manage to form defect-free helices is
a function of both chain length and cooling rate. In order to demonstrate
behavior analogous to the formation of protein tertiary structure, additional
attractive interactions are introduced into the model, leading to the
appearance of aligned, antiparallel helix pairs. The simulations employ a
computational approach that deals directly with the internal coordinates in a
recursive manner; this representation is able to maintain constant bond lengths
and angles without the necessity of treating them as an algebraic constraint
problem supplementary to the equations of motion.Comment: 15 pages, 14 figure
Diagnostic accuracy of follow-up tests for detecting colorectal cancer recurrences in primary care:A systematic review and meta-analysis
Introduction
Traditionally, follow-up of colorectal cancer (CRC) is performed in secondary care. In new models of care, the screening part care could be replaced to primary care. We aimed to synthesise evidence on the diagnostic accuracy of commonly used screeners in CRC follow-up applicable in primary care: carcinoembryonic antigen (CEA), ultrasound and physical examination.
Methods
Medline, EMBASE, Cochrane Trial Register and Web of Science databases were systematically searched. Studies were included if they provided sufficient data for a 2 Ă— 2 contingency tables. QUADAS-2 was used to assess methodological quality. We performed bivariate random effects meta-analysis, generated a hypothetical cohort, and reported sensitivity and specificity.
Results
We included 12 studies (n = 3223, median recurrence rate 19.6%). Pooled estimates showed a sensitivity for CEA (≤ 5 μg/l) of 59% [47%–70%] and a specificity of 89% [80%–95%]. Only few studies reported sensitivities and specificities for ultrasound (36–70% and 97–100%, respectively) and clinical examination (23% and 27%, respectively).
Conclusion
In practice, GPs could perform CEA screening. Radiological examination in a hospital setting should remain part of the surveillance strategy. Personalised algorithms accounting for recurrence risk and changes of CEA-values over time might add to the diagnostic value of CEA in primary care
Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins
Bioinorganic canon states that active-site
thiolate coordination promotes rapid electron transfer (ET)
to and from type 1 copper proteins. In recent work, we have
found that copper ET sites in proteins also can be constructed
without thiolate ligation (called “type zero” sites). Here we
report multifrequency electron paramagnetic resonance
(EPR), magnetic circular dichroism (MCD), and nuclear
magnetic resonance (NMR) spectroscopic data together with
density functional theory (DFT) and spectroscopy-oriented
configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type
zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers
relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1
centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the
orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding
- …