Crawling of a driven adherent membrane.

We discuss motions of an elastic N × M membrane model whose constituents can bind reversibly with strength ε to adhesive sites of a flat substrate. One of the edges of the membrane ("front") is driven in one direction at rate constant p by N stochastically treadmilling short parallel lines ("cortex"). The main conclusions derived from Monte Carlo studies of this model are the following: (a) Since the polymerizing cortex pushes only the leading edge of the membrane, the major part of the membranes is dragged behind. Therefore, the locomotion of the membrane can be described by frictional sliding processes which are asymmetrically distributed between front and rear of the membrane. A signature of this asymmetry is the difference between the life times of adhesion bonds at front and rear, τ(1) and τ(M), respectively, where τ(1) ≫ τ(M). (b) There are four characteristic times for the membrane motion: The first time, T(0) ~ τ(M) ~ e(aε), is the resting time where the displacement of the membrane is practically zero. The second time, T(p) ~ τ(1) ~ M, is the friction time which characterizes the time between two consecutive ruptures of adhesion bonds at the front, and which signalizes the onset of drift ("protrusion") at the leading edge. The third time, T(r) ~ M(γ(ε)) (γ > 1), characterizes the "retraction" of the trailing edge, which is the retarded response to the pulling leading edge. The fourth time, T(L) ~ M(2), is the growth time for fluctuation of the end-to-end distance. (c) The separation of time scales, T(r)/T(p) ~ M(γ(ε) - 1), leads to stretched fluctuations of the end-to-end distance, which are considered as stochastic cycles of protrusion and retraction on the time scale of T(L). (d) The drift velocity v obeys anomalous scaling, v/p~f(p(1/γ(ε))M), where f(z) ~ const. for small drag pM ≪ 1, and f(z) ~ z(-γ(ε)) for pM ≫ 1, which implies v~M(-γ(ε)). These results may also turn out to be useful for the (more difficult) problem of understanding the protrusion-retraction cycle of crawling biological cells. We compare our model and our results to previous two-particle theories for membrane protrusion and to known stochastic friction models.

Dynamics of a driven surface.

We present a Monte Carlo study of an Edwards-Wilkinson type of surface when it is driven by another random surface which drifts with a rate 0

Auditory-motor integration during fast repetition: the neuronal correlates of shadowing.

This fMRI study examined which structures of a proposed dorsal stream system are involved in the auditory-motor integration during fast overt repetition. We used a shadowing task which requires immediate repetition of an auditory-verbal input and is supposed to elicit unconscious imitation effects of phonologically irrelevant speech parameters. Subjects' responses were recorded in the scanner. To examine automated auditory-motor mapping of speech gestures of others onto one's own speech production system we contrasted the shadowing of pseudowords produced by multiple speakers (men, women, and children) with the shadowing of pseudowords produced by a single speaker. Furthermore, we asked whether behavioral variables predicted changes in functional activation during shadowing. Shadowing multiple speakers compared to a single speaker elicited increased bilateral activation predominantly in the superior temporal sulci. These regions may mediate acoustic-phonetic speaker normalization in preparation of a translation of perceptual into motor information. Additional activation in Broca's area and the thalamus may reflect motor effects of the adaptation to multiple speaker models. Item-wise correlational analyses of response latencies with BOLD signal changes indicated that longer latencies were associated with increased activation in the left parietal operculum, suggesting that this area plays a central role in the actual transfer of auditory-verbal information to speech motor representations. A multiple regression of behavioral with imaging data showed activation in a right inferior parietal area near the temporo-parietal boundary which correlated positively with the degree of speech rate imitation and negatively with response latency. This activation may be attributable to attentional and/or paralinguistic processes.

Anomalous diffusion and dynamics of fluorescence recovery after photobleaching in the random-comb model.

We address the problem of diffusion on a comb whose teeth display varying lengths. Specifically, the length ℓ of each tooth is drawn from a probability distribution displaying power law behavior at large ℓ,P(ℓ)∼ℓ^{-(1+α)} (α>0). To start with, we focus on the computation of the anomalous diffusion coefficient for the subdiffusive motion along the backbone. This quantity is subsequently used as an input to compute concentration recovery curves mimicking fluorescence recovery after photobleaching experiments in comblike geometries such as spiny dendrites. Our method is based on the mean-field description provided by the well-tested continuous time random-walk approach for the random-comb model, and the obtained analytical result for the diffusion coefficient is confirmed by numerical simulations of a random walk with finite steps in time and space along the backbone and the teeth. We subsequently incorporate retardation effects arising from binding-unbinding kinetics into our model and obtain a scaling law characterizing the corresponding change in the diffusion coefficient. Finally, we show that recovery curves obtained with the help of the analytical expression for the anomalous diffusion coefficient cannot be fitted perfectly by a model based on scaled Brownian motion, i.e., a standard diffusion equation with a time-dependent diffusion coefficient. However, differences between the exact curves and such fits are small, thereby providing justification for the practical use of models relying on scaled Brownian motion as a fitting procedure for recovery curves arising from particle diffusion in comblike systems.

Mechanisms of discourse comprehension impairment after right hemisphere brain damage: suppression in inferential ambiguity resolution.

This study examined the generality of a previous finding indicating that difficulty suppressing or inhibiting context-inappropriate interpretations is an important predictor of narrative discourse comprehension for adults with right brain damage (RBD) (C. A. Tompkins, A. Baumgaertner, M. T. Lehman, & W. Fassbinder, 2000). Forty adults with RBD and 39 without brain damage listened to two-sentence stimuli and judged whether a probe word fit with the overall stimulus meaning. An ambiguous initial sentence elicited both dominant and less preferred inferences, and the second sentence resolved the ambiguity toward the initially less-likely interpretation. Probes represented the dominant inference for the first sentence and were presented at two poststimulus intervals. Probe judgment response times indicated that neither group suppressed the eventually inappropriate inferences in the time intervals studied. However, multiple regression analysis demonstrated that for individual participants with RBD, the extent of suppression from one interval to the next was a significant predictor of performance on a specialized measure of inference comprehension. The discussion evaluates these findings and identifies directions for future research.

Mechanisms of discourse comprehension impairment after right hemisphere brain damage: suppression in lexical ambiguity resolution.

Normal comprehension skill is linked with the proficiency of a suppression mechanism, which functions to dampen mental activation that becomes irrelevant or inappropriate to a final interpretation. This study investigated suppression and discourse comprehension in adults with right brain damage (RBD). To index suppression function, 40 adults with RBD and 40 without brain damage listened to sentence stimuli that biased the meaning of a sentence-final lexical ambiguity (e.g., SPADE), then judged whether a probe word (e.g., CARDS) fit the overall sentence meaning. Probes represented the contextually inappropriate meanings of the ambiguities and were presented in two conditions: 175 ms and 1000 ms post-stimulus. The same probes were used with unambiguous comparison stimuli. Probe judgment response times indicated that only the group without brain damage suppressed inappropriate interpretations over time. In a multiple regression analysis, suppression function added significantly to predicting performance on a general measure of narrative discourse comprehension for participants with RBD. The discussion addresses how suppression deficits may account more broadly for comprehension difficulties after RBD; it also considers several unresolved issues concerning the suppression construct and the suppression deficit hypothesis.

Malignant melanoma of the anal region.

Malignant melanoma (MM) of the anal region is an uncommon disease. In many cases, the disease is undetected or mistaken for a benign polyp or haemorrhoids until it reaches an advanced state. Owing to delayed diagnosis and early metastases, the prognosis is often poor. In contrast to melanomas of the skin, a history of sun exposure does not seem to have an impact in development of MM in this region. Anorectal melanomas (AM) are most common in the rectum, followed by the anal canal and anal verge. Ras mutations, especially in codon 61 of the N-ras oncogene, are common in CM and rare in melanomas of the vulva and anorectum. The diagnosis of an AM is usually made using a biopsy. Histopathological examinations show spindle-shaped and pleomorphic cells. Adjuvant immunohistological markers are the calcium-binding protein S-100, the melanoma antigen HMB-45, the melanoma-expressed protein Melan A, and microphthalmia-associated transcription factor (MiTF). To date, there are few published guidelines for the correct management of AM, and surgery remains the mainstay of treatment. We report on a 39-year old man who presented with a 5-week history of recurrent prolapse of an anal tumour. The tumour was histologically confirmed to be malignant melanoma.

Autocatalytic polymerization generates persistent random walk of crawling cells.

The autocatalytic polymerization kinetics of the cytoskeletal actin network provides the basic mechanism for a persistent random walk of a crawling cell. It is shown that network remodeling by branching processes near the cell membrane is essential for the bimodal spatial stability of the network which induces a spontaneous breaking of isotropic cell motion. Details of the phenomena are analyzed using a simple polymerization model studied by analytical and simulation methods.

Shape and motility of a model cell: a computational study.

We have investigated the shape, size, and motility of a minimal model of an adherent biological cell using the Monte Carlo method. The cell is modeled as a two dimensional ring polymer on the square lattice enclosing continuously polymerizing and depolymerizing actin networks. Our lattice model is an approximate representation of a real cell at a resolution of one actin molecule, 5 nm. The polymerization kinetics for the actin network are controlled by appropriate reaction probabilities which correspond to the correct experimental reaction rates. Using the simulation data we establish various scaling laws relating the size of the model cell to the concentration of polymerized and unpolymerized actin molecules and the length of the enclosing membrane. The computed drift velocities, which characterize the motility of the cell, exhibit a maximum at a certain fraction of polymerized actin which agrees with physiological fractions observed in experiments. The appearance of the maximum is related to the competition between the polymerization-induced protrusion of the membrane and the concomitant suppression of membrane fluctuations.

Stability of a melittin pore in a lipid bilayer: a molecular dynamics study.

We have investigated the configuration and the stability of a single membrane pore bound by four melittin molecules and embedded in a fully hydrated bilayer lipid membrane. We used molecular dynamics simulations up to 5.8 ns. It is found that the initial tetrameric configuration decays with increasing time into a stable trimer and one monomer. This continuous transformation is accompanied by a lateral expansion of the aqueous pore exhibiting a final size comparable to experimental findings. The expansion-induced formation of an interface between the pore-lining acyl chains of the lipids and the pore water ("hydrophobic pore") is transformed into an energetically more favorable toroidal pore structure where some lipid heads are translocated from the rim to the central part of the interface ("hydrophilic pore"). The expansion of the pore is supported by the electrostatic repulsion among the alpha-helices. It is hypothesized that pore growth, and hence cell lysis, is induced by a melittin-mediated line tension of the pore.

Event-related fMRI reveals cortical sites involved in contextual sentence integration.

We examined the effects of difficulty of sentential integration on blood oxygenation level-dependent contrast changes. Difficulty of integration was operationalized as the degree to which sentence-final nouns matched the expectations generated by preceding context. Nine young adults read short sentence fragments (e.g., "The pilot flies.") which were completed by highly expected nouns (e.g., "the plane"), unexpected yet semantically legal nouns (e.g., "the kite"), nouns that violated the verbs' selection restriction rules (e.g., "the book"), and pseudowords (e.g., "the foop") and made quick lexical decisions on the sentence-final item. Overall, word completions resulted in higher changes in activation than pseudoword completions. The largest of those changes were observed in left angular and posterior middle temporal gyri, suggesting that despite the lexical nature of the task, word stimuli embedded in sentence contexts triggered integrative-semantic processes beyond a lexical level. A region-of-interest analysis in left inferior frontal and left posterior middle temporal areas revealed activation for both unexpected and anomalous completions when compared to expected completions. Thus, while the underlying processing mechanisms may differ, sentential integration appears similarly effortful for these two types of completions. Our findings are consistent with previous reports of local increases in activation as a function of (syntactic) complexity, while extending the findings to processing demands of semantic integration. Because of its sensitivity to changes in semantic congruence and the implicit nature of the task involved, we argue that the present paradigm is well suited to study patients with potential semantic deficits after brain damage.

Translational diffusion of flexible lipid chains in a Langmuir monolayer: a dynamic Monte Carlo study.

We report a computer simulation study of the lateral diffusion of conformationally disordered lipid molecules in a monolayer structure. The simulations were carried out with dynamic Monte Carlo methods, employing two different representations of the internal motions of the lipid chains. The classical Cohen-Turnbull theory is found to provide a good description of the simulated lateral diffusion coefficients at moderate densities. The substantial deviations found at low densities are attributed to the small density fluctuations needed to create the free volume required for the lateral diffusion process.

Working memory and inference revision in brain-damaged and normally aging adults.

This study examined the association between estimated working memory (WM) capacity and comprehension of passages that required revision of an initial interpretation. Predictions stemmed from the recently elaborated theory of capacity-constrained comprehension (Just & Carpenter, 1992, Psychological Review, 99, 122-149), which includes as a major feature the principle that WM influences comprehension only as processing demands approach or exceed the limits of capacity. As anticipated from task analysis, correlations between unilaterally brain-damaged patients' estimated WM capacity and discourse comprehension performance were minimal for nondemanding measures, and increased in magnitude with task processing requirements. Most notably, a meaningful correlation (/r/ greater than .50) emerged only for the task judged to involve the most demanding comprehension processes, for adults with right hemisphere brain damage. No meaningful associations between estimated WM capacity and task performance were observed for normally aging subjects, who were not expected to have difficulty with any of our comprehension measures. The nature of WM deficits in brain-damaged adults (total capacity, vs. resource allocation, vs. slow or otherwise faulty component processing operations) is considered, and some existing work is interpreted from a cognitive resource perspective. Theoretical implications and clinical applicability of the working memory/resource framework are also discussed.