Large deviations of Rouse polymer chain: first passage problem

The purpose of this paper is to investigate several analytical methods of solving first passage (FP) problem for the Rouse model, a simplest model of a polymer chain. We show that this problem has to be treated as a multi-dimensional Kramers' problem, which presents rich and unexpected behavior. We first perform direct and forward-flux sampling (FFS) simulations, and measure the mean first-passage time $\tau(z)$ for the free end to reach a certain distance $z$ away from the origin. The results show that the mean FP time is getting faster if the Rouse chain is represented by more beads. Two scaling regimes of $\tau(z)$ are observed, with transition between them varying as a function of chain length. We use these simulations results to test two theoretical approaches. One is a well known asymptotic theory valid in the limit of zero temperature. We show that this limit corresponds to fully extended chain when each chain segment is stretched, which is not particularly realistic. A new theory based on the well known Freidlin-Wentzell theory is proposed, where dynamics is projected onto the minimal action path. The new theory predicts both scaling regimes correctly, but fails to get the correct numerical prefactor in the first regime. Combining our theory with the FFS simulations lead us to a simple analytical expression valid for all extensions and chain lengths. One of the applications of polymer FP problem occurs in the context of branched polymer rheology. In this paper, we consider the arm-retraction mechanism in the tube model, which maps exactly on the model we have solved. The results are compared to the Milner-McLeish theory without constraint release, which is found to overestimate FP time by a factor of 10 or more.

Ação de extratos aquoso e alcoólico de própolis sobre Malassezia spp isoladas do conduto auditivo de cães

Pós-graduação em Medicina Veterinária - FMVZ

Generation of representation models for complex systems using Lagrangian functions

In this article, a new methodology is presented to obtain representation models for a priori relation z = u(x1, x2, . . . ,xn) (1), with a known an experimental dataset zi; x1i ; x2i ; x3i ; . . . ; xni i=1;2;...;p· In this methodology, a potential energy is initially defined over each possible model for the relationship (1), what allows the application of the Lagrangian mechanics to the derived system. The solution of the Euler–Lagrange in this system allows obtaining the optimal solution according to the minimal action principle. The defined Lagrangian, corresponds to a continuous medium, where a n-dimensional finite elements model has been applied, so it is possible to get a solution for the problem solving a compatible and determined linear symmetric equation system. The computational implementation of the methodology has resulted in an improvement in the process of get representation models obtained and published previously by the authors.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Action Of Essential Oils From Brazilian Native And Exotic Medicinal Species On Oral Biofilms.

Essential oils (EO) obtained from twenty medicinal and aromatic plants were evaluated for their antimicrobial activity against the oral pathogens Candida albicans, Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus sanguis and Streptococcus mitis. The antimicrobial activity of the EO was evaluates by microdilution method determining Minimal Inhibitory Concentration. Chemical analysis of the oils compounds was performed by Gas chromatography-mass spectrometry (CG-MS). The most active EO were also investigated as to their actions on the biolfilm formation. The most of the essential oils (EO) presented moderate to strong antimicrobial activity against the oral pathogens (MIC--Minimal Inhibitory Concentrations values between 0.007 and 1.00 mg/mL). The essential oil from Coriandrum sativum inhibited all oral species with MIC values from 0.007 to 0.250 mg/mL, and MBC/MFC (Minimal Bactericidal/Fungicidal Concentrations) from 0.015 to 0.500 mg/mL. On the other hand the essential oil of C. articulatus inhibited 63.96% of S. sanguis biofilm formation. Through Scanning Eletronic Microscopy (SEM) images no changes were observed in cell morphology, despite a decrease in biofilm formation and changes on biofilm structure. Chemical analysis by Gas Chromatography-Mass Spectrometry (GC-MS) of the C. sativum essential oil revealed major compounds derivatives from alcohols and aldehydes, while Cyperus articulatus and Aloysia gratissima (EOs) presented mono and sesquiterpenes. In conclusion, the crude oil from C. articulatus exhibited the best results of antimicrobial activity e ability to control biofilm formation. The chemical analysis showed the presence of terpenes and monoterpenes such as a-pinene, a-bulnesene and copaene. The reduction of biofilms formation was confirmed from SEM images. The results of this research shows a great potential from the plants studied as new antimicrobial sources.

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Background Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and Methods We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. Results At least one marker was detected by polymerase chain reaction in 96.4%, of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%,, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. Conclusions This simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

Reversal of the silencing of tetracycline-controlled genes requires the coordinate action of distinctly acting transcription factors.

BACKGROUND: Regulation of genes transferred to eukaryotic organisms is often limited by the lack of consistent expression levels in all transduced cells, which may result in part from epigenetic gene silencing effects. This reduces the efficacy of ligand-controlled gene switches designed for somatic gene transfers such as gene therapy. METHODS: A doxycycline-controlled transgene was stably introduced in human cells, and clones were screened for epigenetic silencing of the transgene. Various regulatory proteins were targeted to the silent transgene, to identify those that would mediate regulation by doxycycline. RESULTS: A doxycycline-controlled minimal promoter was found to be prone to gene silencing, which prevents activation by a fusion of the bacterial TetR DNA-binding domain with the VP16 activator. DNA modification studies indicated that the silenced transgene adopts a poorly accessible chromatin structure. Several cellular transcriptional activators were found to restore an accessible DNA structure when targeted to the silent transgene, and they cooperated with Tet-VP16 to mediate regulation by doxycycline. CONCLUSIONS: Reversal of the silencing of a tetracycline-regulated minimal promoter requires a chromatin-remodeling activity for subsequent promoter activation by the Tet-VP16 fusion protein. Thus, distinct regulatory elements may be combined to obtain long-term regulation and persistent expression of exogenous genes in eukaryotic cells.

"In vitro" comparative experimental study of antimicrobial action of mouth washing products

Regular use of mouth rinses modifies the oral habitat, since bacterial populations are submitted to a high selective pressure during the treatment exercised by the active presence of the disinfectant. Mostly mouth rinses are based on the antibacterial effect of Chlorhexidine, Triclosan, essential oils and other antibacterials although other pharmaceutical characteristics can also affect their effectiveness. In this paper we compare"in vitro" the antibacterial effect of different oral rinsing solutions. Minimal Inhibitory Concentrations (MIC) and Minimal Bactericidal Concentrations (MBC) were determined as well as the kinetics of bacterial death in the presence of letal concentrations of the mouth rinses. MIC values expressed as Maximal Inhibitory Dilution (MID) of the mouth rinse ranged from 1 to 1/2048 depending on the microorganism and product, whereas Minimal Biocidal Concentration (MBC), expressed as Maximal Biocidal Dilution (MBD) ranged from 1 to 1/1024, being in general one dilution less than MIC. Maximal Biocidal Dilution is a good tool to measure the actual efficiency of mouth washing solutions. However, kinetics of death seems to be better in our work killing curves demonstrate that bacterial populations are mostly eliminated during the first minute after the contact of bacterial suspension and the mouth-washing solution. In all tested bacterial species mouth-washing solutions tested were able to reduce until suspension treated except 1 and 5

Multiloop superstring amplitudes from non-minimal pure spinor formalism

Using the non-minimal version of the pure spinor formalism, manifestly super-Poincare covariant superstring scattering amplitudes can be computed as in topological string theory without the need of picture-changing operators. The only subtlety comes from regularizing the functional integral over the pure spinor ghosts. In this paper, it is shown how to regularize this functional integral in a BRST-invariant manner, allowing the computation of arbitrary multiloop amplitudes. The regularization method simplifies for scattering amplitudes which contribute to ten-dimensional F-terms, i.e. terms in the ten-dimensional superspace action which do not involve integration over the maximum number of theta's.

BFFT formalism applied to the minimal chiral Schwinger model

We consider the minimal chiral Schwinger model, by embedding the gauge non-invariant formulation into a gauge theory following the Batalin-Fradkin-Fradkina-Tyutin point of view. Within the BFFT procedure, the second-class constraints are converted into strongly involutive first-class ones, leading to an extended gauge-invariant formulation. We also show that, like the standard chiral model, in the minimal chiral model the Wess-Zumino action can be obtained by performing a q-number gauge transformation into the effective gauge non-invariant action.

On the meaning of the minimal Wess-Zumino term

The physical meaning of the recently proposed minimal Wess-Zumino (MWZ) term is discussed. It is shown that the only relativistically acceptable MWZ corresponds to a gauged Floreanini-Jackiw chiral boson. This leads to the conclusion that the very mechanism in action is that of closing families like it happens in the standard model, and not that of the WZ term, in the spirit of Faddeev-Shatashvilli.

Microneurography in rats: a minimally invasive method to record single C-fiber action potentials from peripheral nerves in vivo

Microneurography is a method suitable for recording intraneural single or multiunit action potentials in conscious subjects. Microneurography has rarely been applied to animal experiments, where more invasive methods, like the teased fiber recording technique, are widely used. We have tested the feasibility of microneurographic recordings from the peripheral nerves of rats. Tungsten microelectrodes were inserted into the sciatic nerve at mid-thigh level. Single or multiunit action potentials evoked by regular electrical stimulation were recorded, digitized and displayed as a raster plot of latencies. The method allows unambiguous recording and recognition of single C-fiber action potentials from an in vivo preparation, with minimal disruption of the nerve being recorded. Multiple C-fibers can be recorded simultaneously for several hours, and if the animal is allowed to recover, repeated recording sessions can be obtained from the same nerve at the same level over a period of weeks or months. Also, single C units can be functionally identified by their changes in latency to natural stimuli, and insensitive units can be recognized as 'silent' nociceptors or sympathetic efferents by their distinctive profiles of activity-dependent slowing during repetitive electrical stimulation, or by the effect on spontaneous efferent activity of a proximal anesthetic block. Moreover, information about the biophysical properties of C axons can be obtained from their latency recovery cycles. Finally, we show that this preparation is potentially suitable for the study of C-fiber behavior in models of neuropathies and nerve lesions, both under resting conditions and in response to drug administration.

Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells.

Simultaneous recordings from the soma and apical dendrite of layer V neocortical pyramidal cells of young rats show that, for any location of current input, an evoked action potential (AP) always starts at the axon and then propagates actively, but decrementally, backward into the dendrites. This back-propagating AP is supported by a low density (-gNa = approximately 4 mS/cm2) of rapidly inactivating voltage-dependent Na+ channels in the soma and the apical dendrite. Investigation of detailed, biophysically constrained, models of reconstructed pyramidal cells shows the following. (i) The initiation of the AP first in the axon cannot be explained solely by morphological considerations; the axon must be more excitable than the soma and dendrites. (ii) The minimal Na+ channel density in the axon that fully accounts for the experimental results is about 20-times that of the soma. If -gNa in the axon hillock and initial segment is the same as in the soma [as recently suggested by Colbert and Johnston [Colbert, C. M. & Johnston, D. (1995) Soc. Neurosci. Abstr. 21, 684.2]], then -gNa in the more distal axonal regions is required to be about 40-times that of the soma. (iii) A backward propagating AP in weakly excitable dendrites can be modulated in a graded manner by background synaptic activity. The functional role of weakly excitable dendrites and a more excitable axon for forward synaptic integration and for backward, global, communication between the axon and the dendrites is discussed.

Optimal preventive maintenance of leased equipment with corrective minimal repairs

For leased equipment, the lessor carries out the maintenance of the equipment. Usually, the contract of lease specifies the penalty for equipment failures and for repairs not being carried out within specified time limits. This implies that optimal preventive maintenance policies must take these penalty costs into account and properly traded against the cost of preventive maintenance actions. The costs associated with failures are high as unplanned corrective maintenance actions are costly and the resulting penalties due to lease contract terms being violated. The paper develops a model to determine the optimal parameters of a preventive maintenance policy that takes into account all these costs to minimize the total expected cost to the lessor for new item lease. The parameters of the policy are (i) the number of preventive maintenance actions to be carried out over the lease period, (ii) the time instants for such actions, and (iii) the level of action. (c) 2005 Elsevier B.V. All rights reserved.

Restaurant Industry Perspectives on Pro-social Rule Breaking: Intent versus Action

The resounding message extracted from the service literature is that employees serve pivotal functions in the overall guest experience. This is of course due to the simultaneous delivery of personalized service provision with resultant consumption of those services. This simultaneous delivery and consumption cycle is at times challenged by a perceived desire to accommodate guest request that may violate, to a greater or lesser degree, an organizational rule. This is important to note because increased interactions with customers enable frontline employees to have a better sense of what customers want from the company as well as from the company itself (Bitner, et al, 1994). With that platform established, then why are some employees willing to break organizational rules and risk disciplinary action to better service a customer? This study examines the employee personality, degree of autonomy, job meaning, and co-worker influence on an employee's decision to break organizational rules. The results of this study indicate that co-worker influence exerted a minimal influence on employee decision to break rules while the presence of societal consciousness exerted a much stronger influence. Women reported that they were less likely to engage in rule divergence, and significant correlations were present when filtered by years in current position, and years in the industry.