Dumbbell diffusion in a spatially periodic potential

We present a numerical investigation of the Brownian motion and diffusion of a dumbbell in a two-dimensional periodic potential. Its dynamics is described by a Langevin model including the hydrodynamic interaction. With increasing values of the amplitude of the potential we find along the modulated spatial directions a reduction of the diffusion constant and of the impact of the hydrodynamic interaction. For modulation amplitudes of the potential in the range of the thermal energy the dumbbell diffusion exhibits a pronounced local maximum at a wavelength of about 3/2 of the dumbbell extension. This is especially emphasized for stiff springs connecting the two beads.Comment: 4 pages, 7 figures, published in Phys. Rev. E (2008

Direct measurement of shear-induced cross-correlations of Brownian motion

Shear-induced cross-correlations of particle fluctuations perpendicular and along stream-lines are investigated experimentally and theoretically. Direct measurements of the Brownian motion of micron-sized beads, held by optical tweezers in a shear-flow cell, show a strong time-asymmetry in the cross-correlation, which is caused by the non-normal amplification of fluctuations. Complementary measurements on the single particle probability distribution substantiate this behavior and both results are consistent with a Langevin model. In addition, a shear-induced anti-correlation between orthogonal random-displacements of two trapped and hydrodynamically interacting particles is detected, having one or two extrema in time, depending on the positions of the particles.Comment: 4 pages, 4 figure

\u3ci\u3e Quantification of protoporphyrin IX accumulation in glioblastoma cells – A new technique \u3c/i\u3e

Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After treatment with a series of 5-ALA doses, both PpIX and YFP fluorescence were measured. The ratio of PpIX to YFP fluorescence was calculated. Results. YFP fluorescence permitted the quantification of cell numbers and did not interfere with 5-ALA metabolism. The PpIX/YFP fluorescence ratio provided accurate relative PpIX levels, allowing for the assessment of PpIX accumulation in tissue. Conclusion. Constitutive YFP expression strongly correlates with cell number and permits PpIX quantification. Absolute PpIX fluorescence alone does not provide information regarding PpIX accumulation within the cells. Our research indicates that our PpIX/YFP ratio assay may be a promising model for in vitro 5-ALA testing and its interactions with other compounds during FGR surgery

Stripe-hexagon competition in forced pattern forming systems with broken up-down symmetry

We investigate the response of two-dimensional pattern forming systems with a broken up-down symmetry, such as chemical reactions, to spatially resonant forcing and propose related experiments. The nonlinear behavior immediately above threshold is analyzed in terms of amplitude equations suggested for a $1:2$ and $1:1$ ratio between the wavelength of the spatial periodic forcing and the wavelength of the pattern of the respective system. Both sets of coupled amplitude equations are derived by a perturbative method from the Lengyel-Epstein model describing a chemical reaction showing Turing patterns, which gives us the opportunity to relate the generic response scenarios to a specific pattern forming system. The nonlinear competition between stripe patterns and distorted hexagons is explored and their range of existence, stability and coexistence is determined. Whereas without modulations hexagonal patterns are always preferred near onset of pattern formation, single mode solutions (stripes) are favored close to threshold for modulation amplitudes beyond some critical value. Hence distorted hexagons only occur in a finite range of the control parameter and their interval of existence shrinks to zero with increasing values of the modulation amplitude. Furthermore depending on the modulation amplitude the transition between stripes and distorted hexagons is either sub- or supercritical.Comment: 10 pages, 12 figures, submitted to Physical Review

A Genetically Hard-Wired Metabolic Transcriptome in Plasmodium falciparum Fails to Mount Protective Responses to Lethal Antifolates

Genome sequences of Plasmodium falciparum allow for global analysis of drug responses to antimalarial agents. It was of interest to learn how DNA microarrays may be used to study drug action in malaria parasites. In one large, tightly controlled study involving 123 microarray hybridizations between cDNA from isogenic drug-sensitive and drug-resistant parasites, a lethal antifolate (WR99210) failed to over-produce RNA for the genetically proven principal target, dihydrofolate reductase-thymidylate synthase (DHFR-TS). This transcriptional rigidity carried over to metabolically related RNA encoding folate and pyrimidine biosynthesis, as well as to the rest of the parasite genome. No genes were reproducibly up-regulated by more than 2-fold until 24 h after initial drug exposure, even though clonal viability decreased by 50% within 6 h. We predicted and showed that while the parasites do not mount protective transcriptional responses to antifolates in real time, P. falciparum cells transfected with human DHFR gene, and adapted to long-term WR99210 exposure, adjusted the hard-wired transcriptome itself to thrive in the presence of the drug. A system-wide incapacity for changing RNA levels in response to specific metabolic perturbations may contribute to selective vulnerabilities of Plasmodium falciparum to lethal antimetabolites. In addition, such regulation affects how DNA microarrays are used to understand the mode of action of antimetabolites