Understanding Performance Pedigree.

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Three and four current reversals versus temperature in correlation ratchets with a simple sawtooh potential

Transport of Brownian particles on a simple sawtooth potential subjected to both unbiased thermal and nonequilibrium symmetric three-level Markovian noise is considered. The new effects of three and four current reversals as a function of temperature are established in such correlation ratchets. The parameter space coordinates of the fixed points associated with these current reversals and the necessary and sufficient conditions for the existence of the novel current reversals are found.Comment: 4 pages, 5 figures; some changes introduced; accepted for publication in Physical Review

Diffusion and Current of Brownian Particles in Tilted Piecewise Linear Potentials: Amplification and Coherence

Overdamped motion of Brownian particles in tilted piecewise linear periodic potentials is considered. Explicit algebraic expressions for the diffusion coefficient, current, and coherence level of Brownian transport are derived. Their dependencies on temperature, tilting force, and the shape of the potential are analyzed. The necessary and sufficient conditions for the non-monotonic behavior of the diffusion coefficient as a function of temperature are determined. The diffusion coefficient and coherence level are found to be extremely sensitive to the asymmetry of the potential. It is established that at the values of the external force, for which the enhancement of diffusion is most rapid, the level of coherence has a wide plateau at low temperatures with the value of the Peclet factor 2. An interpretation of the amplification of diffusion in comparison with free thermal diffusion in terms of probability distribution is proposed.Comment: To appear in PR

Gibbs attractor: a chaotic nearly Hamiltonian system, driven by external harmonic force

A chaotic autonomous Hamiltonian systems, perturbed by small damping and small external force, harmonically dependent on time, can acquire a strange attractor with properties similar to that of the canonical distribution - the Gibbs attractor. The evolution of the energy in such systems can be described as the energy diffusion. For the nonlinear Pullen - Edmonds oscillator with two degrees of freedom the properties of the Gibbs attractor and their dependence on parameters of the perturbation are studied both analytically and numerically.Comment: 8 pages RevTeX, 3 figure

MicroRNA-155 expression is independently predictive of outcome in chordoma.

BackgroundChordoma pathogenesis remains poorly understood. In this study, we aimed to evaluate the relationships between microRNA-155 (miR-155) expression and the clinicopathological features of chordoma patients, and to evaluate the functional role of miR-155 in chordoma.MethodsThe miRNA expression profiles were analyzed using miRNA microarray assays. Regulatory activity of miR-155 was assessed using bioinformatic tools. miR-155 expression levels were validated by reverse transcription-polymerase chain reaction. The relationships between miR-155 expression and the clinicopathological features of chordoma patients were analyzed. Proliferative, migratory and invasive activities were assessed by MTT, wound healing, and Matrigel invasion assays, respectively.ResultsThe miRNA microarray assay revealed miR-155 to be highly expressed and biologically active in chordoma. miR-155 expression in chordoma tissues was significantly elevated, and this expression correlated significantly with disease stage (p = 0.036) and the presence of metastasis (p = 0.035). miR-155 expression also correlated significantly with poor outcomes for chordoma patients (hazard ratio, 5.32; p = 0.045). Inhibition of miR-155 expression suppressed proliferation, and the migratory and invasive activities of chordoma cells.ConclusionsWe have shown miR-155 expression to independently affect prognosis in chordoma. These results collectively indicate that miR-155 expression may serve not only as a prognostic marker, but also as a potential therapeutic target in chordoma

Comparison of QG-Induced Dispersion with Standard Physics Effects

One of the predictions of quantum gravity phenomenology is that, in situations where Planck-scale physics and the notion of a quantum spacetime are relevant, field propagation will be described by a modified set of laws. Descriptions of the underlying mechanism differ from model to model, but a general feature is that electromagnetic waves will have non-trivial dispersion relations. A physical phenomenon that offers the possibility of experimentally testing these ideas in the foreseeable future is the propagation of high-energy gamma rays from GRB's at cosmological distances. With the observation of non-standard dispersion relations within experimental reach, it is thus important to find out whether there are competing effects that could either mask or be mistaken for this one. In this letter, we consider possible effects from standard physics, due to electromagnetic interactions, classical as well as quantum, and coupling to classical geometry. Our results indicate that, for currently observed gamma-ray energies and estimates of cosmological parameter values, those effects are much smaller than the quantum gravity one if the latter is first-order in the energy; some corrections are comparable in magnitude with the second-order quantum gravity ones, but they have a very different energy dependence.Comment: 8 pages; Version to be published in CQG as a letter; Includes some new comments and references, but no changes in the result

Chemical engineering of the peptidyl transferase center reveals an important role of the 2′-hydroxyl group of A2451

The main enzymatic reaction of the large ribosomal subunit is peptide bond formation. Ribosome crystallography showed that A2451 of 23S rRNA makes the closest approach to the attacking amino group of aminoacyl-tRNA. Mutations of A2451 had relatively small effects on transpeptidation and failed to unequivocally identify the crucial functional group(s). Here, we employed an in vitro reconstitution system for chemical engineering the peptidyl transferase center by introducing non-natural nucleosides at position A2451. This allowed us to investigate the peptidyl transfer reaction performed by a ribosome that contained a modified nucleoside at the active site. The main finding is that ribosomes carrying a 2′-deoxyribose at A2451 showed a compromised peptidyl transferase activity. In variance, adenine base modifications and even the removal of the entire nucleobase at A2451 had only little impact on peptide bond formation, as long as the 2′-hydroxyl was present. This implicates a functional or structural role of the 2′-hydroxyl group at A2451 for transpeptidation

Uncommon cause for anterior knee pain - Aggressive aneurysmal bone cyst of the patella

A 56-year-old man presented with a two month history of increasing anterior knee pain without previous trauma. As usual we recommended physiotherapy with stretching exercises of the quadriceps muscle. Since symptoms did not improve after 6 weeks MRI was performed. Surprisingly a hyperintense lobulated mass of the patella with small fluid-filled cavities at the inferior pole was revealed. We performed an open biopsy to exclude any malignancy and diagnosed an aneurysmal bone cyst. Further examination with CT scans showed an aggressive behaviour with cortical breakthrough

An antimicrobial peptide that inhibits translation by trapping release factor trap.

Apidaecin (Api) belongs to the group of proline-rich antimicrobial peptides (PrAMPs), which are produced by insects and mammals and protect the host from bacterial infection. PrAMPs enter the bacterial cell, bind to the ribosome, and inhibit protein synthesis. Biochemical characterization and recent high-resolution crystal structures have shown that most PrAMPs obstruct the nascent peptide exit tunnel and the peptidyl transferase center in the ribosome and block the initiation step of translation. Despite the lack of the structural information about the Api-bound ribosome, its similarities with the other PrAMPs suggested that Api also inhibits translation initiation. However, our toeprinting experiments in a cell free translation system revealed that Api does not inhibit initiation but, instead, stalls the ribosome at the stop codon. Isolation of Api-resistant E. coli mutants with alterations in class-1 release factors RF1 and RF2, indicated that Api may interfere with the functions of these factors and/or their association with the ribosome. Consistently, our high-resolution cryo-EM structures of ribosomes complexed with Api showed that Api establishes interactions with the ribosomal exit tunnel and with the functionally important conserved GGQ motif of RF1. Furthermore, kinetic studies revealed that Api does not prevent the release of the nascent peptide chain but impedes the dissociation of RF from its binding site in the ribosome. By trapping RF1 and RF2 in the ribosome, Api leads to depletion of free class-1 RFs in the cell, resulting in inhibition of protein synthesis and cell growth arrest. Importantly, the Api-dependent depletion of RFs facilitates premature stop codon read-through. We envision the possibility that similar trapping of RFs on eukaryotic ribosomes could aid in relieving the effects of human genetic diseases caused by premature stop-codons

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future