Positive Feedback Regulation Results in Spatial Clustering and Fast Spreading of Active Signaling Molecules on a Cell Membrane

Positive feedback regulation is ubiquitous in cell signaling networks, often leading to binary outcomes in response to graded stimuli. However, the role of such feedbacks in clustering, and in spatial spreading of activated molecules, has come to be appreciated only recently. We focus on the latter, using a simple model developed in the context of Ras activation with competing negative and positive feedback mechanisms. We find that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength). The advancing fronts of the clusters of the activated species are rough, with scaling consistent with the Kardar-Parisi-Zhang (KPZ) equation in one dimension. Our minimal model is general enough to describe signal transduction in a wide variety of biological networks where activity in the membrane-proximal region is subject to feedback regulation.Comment: 37 pages, 8 figures. Journal of Chemical Physics (in press

Structure Space of Model Proteins --A Principle Component Analysis

We study the space of all compact structures on a two-dimensional square lattice of size $N=6\times6$. Each structure is mapped onto a vector in $N$-dimensions according to a hydrophobic model. Previous work has shown that the designabilities of structures are closely related to the distribution of the structure vectors in the $N$-dimensional space, with highly designable structures predominantly found in low density regions. We use principal component analysis to probe and characterize the distribution of structure vectors, and find a non-uniform density with a single peak. Interestingly, the principal axes of this peak are almost aligned with Fourier eigenvectors, and the corresponding Fourier eigenvalues go to zero continuously at the wave-number for alternating patterns ($q=\pi$). These observations provide a stepping stone for an analytic description of the distribution of structural points, and open the possibility of estimating designabilities of realistic structures by simply Fourier transforming the hydrophobicities of the corresponding sequences.Comment: 14 pages, 12 figures, Conclusion has been modifie

First Passage Distributions in a Collective Model of Anomalous Diffusion with Tunable Exponent

We consider a model system in which anomalous diffusion is generated by superposition of underlying linear modes with a broad range of relaxation times. In the language of Gaussian polymers, our model corresponds to Rouse (Fourier) modes whose friction coefficients scale as wavenumber to the power $2-z$. A single (tagged) monomer then executes subdiffusion over a broad range of time scales, and its mean square displacement increases as $t^\alpha$ with $\alpha=1/z$. To demonstrate non-trivial aspects of the model, we numerically study the absorption of the tagged particle in one dimension near an absorbing boundary or in the interval between two such boundaries. We obtain absorption probability densities as a function of time, as well as the position-dependent distribution for unabsorbed particles, at several values of $\alpha$. Each of these properties has features characterized by exponents that depend on $\alpha$. Characteristic distributions found for different values of $\alpha$ have similar qualitative features, but are not simply related quantitatively. Comparison of the motion of translocation coordinate of a polymer moving through a pore in a membrane with the diffusing tagged monomer with identical $\alpha$ also reveals quantitative differences.Comment: LaTeX, 10 pages, 8 eps figure

Synthesis and biological activity of some heterocyclic compounds contains N-benzylidene heterocycle and beta-lactam moiety

A number of N-benzylidene heterocycle derivatives have been synthesized and their antibacterial activities tested. The new chemical structures synthesized compounds were verified on the basis of spectral and elemental methods of analyses.the antimicrobial activity of the compounds was done by disc diffusion method We synthesized two different types of compounds, a combination of compounds based on the structure of isatin and other compounds based on the structure of thiazole. Synthesis of thiazole was performed using green chemistry method and a three-step reaction was used in the synthesis of isatin compounds. We used the Stoell-Becker method to synthesize compounds based on the isatin structure. The synthesized product was characterized by its physical properties, melting point, TLC and then subjected to the in vitro antibacterial activities against gram-positive and gram-negative strains of microbe

Synthesis, structural characterization and biological activity of Cu(II), Co(II) and Ni(II) complexes derived from 2-(thiazol-2-ylimino)thiazolidin-4-one ligand

A novel series of metal complexes of 2-(thiazol-2-ylimino) thiazolidin-4-one ligand were prepared; the corresponding ligand was synthesized from reaction 2-Chloro-N-(thiazol-2-yl) acetamide with ammonium thiocyanate. The complexes are characterized by FTIR, UV-Vis, molar conductance and mass spectroscopy. The low molar conductance values indicate that the complexes are non-electrolytes.Spectroscopic studies confirmed that the ligand bonded to the metals through the sulphur atoms. Coordination number of copper and nickel complexes is four with square planar geometry, while the cobalt complex has octahedral geometry.In vitro antibacterial activity of ligand and its metal complexes was evaluated using well diffusion method and compared to the standard drug (tetracycline). The antibacterial activitywas examined against Escherichia coli, and pseudomonas aeruginosa, as gram negative bacteria and Staphylococcus aureus as gram positive bacteria. It was found that Nickel complex has the highest antibacterial activity among the synthesized compounds with Zone inhibition diameter in the range 25-29 mm

Monitoring Service Level Workload of Highly Available Applications

Elasticity is a key feature of cloud computation and is a major contributor to its popularity. Elasticity is defined as automatic provisioning/de-provisioning of resources to match workload changes over time. Service High Availability (HA) is among one of cloud computing’s big challenges. High Availability (HA) is defined as providing a minimum of 99.999% service availability. Maintaining service HA while scaling in/out is even more challenging. Recently, an architecture has been proposed for managing HA. Following the proposed architecture, an Elasticity Engine has been introduced that is capable of managing resources based on application level provisioning or de-provisioning alerts while preserving HA. In contrast to the prevailing monitoring solutions where Virtual Machine (VM) level workload is provided, the Elasticity Engine requires a monitoring solution that monitors service-level workload and triggers alerts accordingly. In this thesis, we propose an approach and an architecture for the monitoring of HA applications at the service level. Accordingly, the monitoring approach starts with monitoring the application components in traditional manner. Workload of the components are mapped to each component’s respective service assignment. The resource usages of all the components providing services is aggregated and mapped to the service level workload using a distributed client-server architecture. This approach allows for distinguishing between the different HA states, active or standby that a component can be assigned at runtime and it (the approach) adapts to the situations where switchovers happen under the control of the SA Forum middleware due to failures for example. The proposed monitoring architecture has been implemented and integrated with the Elasticity Engine to test its effectiveness and overhead. It has been shown that the implemented and integrated prototypes achieve elasticity in a cluster based on service level workload while keeping the monitoring overhead within 5% of its total resource

The zona incerta in control of novelty seeking and investigation across species

Many organisms rely on a capacity to rapidly replicate, disperse, and evolve when faced with uncertainty and novelty. But mammals do not evolve and replicate quickly. They rely on a sophisticated nervous system to generate predictions and select responses when confronted with these challenges. An important component of their behavioral repertoire is the adaptive context-dependent seeking or avoiding of perceptually novel objects, even when their values have not yet been learned. Here, we outline recent cross-species breakthroughs that shed light on how the zona incerta (ZI), a relatively evolutionarily conserved brain area, supports novelty-seeking and novelty-related investigations. We then conjecture how the architecture of the ZI\u27s anatomical connectivity - the wide-ranging top-down cortical inputs to the ZI, and its specifically strong outputs to both the brainstem action controllers and to brain areas involved in action value learning - place the ZI in a unique role at the intersection of cognitive control and learning

Comparing efficacy of montelukast versus doxycycline in treatment of moderate acne

Background: Treatment of acne is an important issue for reducing the cosmetic and psychological burden of disease. Regarding the inflammatory effect of LT-B4 in acne lesions and action mechanism of Montelukast, this study was performed to determine the efficacy of Montelukastin acne treatment comparison with doxycycline. Materials and Methods: In a randomized clinical trial that was performed in Dermatology Clinic in a Training Tertiary Health Care Center in Tehran, Iran since January 2012 to May 2014, 52 patients with moderate acne were evaluated. The included patients were randomly assigned to receive doxycycline 100 mg/day plus 1 Clindamycin solution (Group 1) or Montelukast 5 mg daily plus 1 clindamycin solution (Group 2). The acne severity index was measured and compared between two groups at baseline (on admission), 1-month and 3 months later. Independent-Sample-T, Chi-Square, and Repeated-Measure ANOVA tests were used and were considered statistically significant at P < 0.05. Results: The mean age was 26.8 ± 7.1 in Group 1 and25 ± 4.8 in Group 2 (P = 0.1). 73 women and 26.7 4 men in Group 1 and 86.7 women, and 13.3 men in Group 2 (P = 0.01). The mean acne severity index at baseline was 18.2 ± 6.1 and 19 ± 4.2 in Montelukast and doxycycline group, respectively (P = 0.679). The mean acne severity index after 1-month was 10.5 ± 6.2 and 12.9 ± 3.3 in Montelukast and doxycycline group, respectively (P = 0). Finally, the mean acne severity index after 3 months follow-up was 8.6 ± 4.8 and 8.2 ± 1.2 in Montelukast and doxycycline group, respectively (P = 0.01). There was no significant difference between two groups regarding the amount of decrease in acne severity index across the study (P = 0.186). However, each groups showed a significant reduction in the acne severity index, separately (P = 0.001). Conclusion: It may be concluded that Montelukast is an effective and safe medication for moderate-level acne treatment. © 2015, Isfahan University of Medical Sciences(IUMS). All rights reserved

Polymer-mediated entropic forces between scale-free objects

The number of configurations of a polymer is reduced in the presence of a barrier or an obstacle. The resulting loss of entropy adds a repulsive component to other forces generated by interaction potentials. When the obstructions are scale invariant shapes (such as cones, wedges, lines or planes) the only relevant length scales are the polymer size R_0 and characteristic separations, severely constraining the functional form of entropic forces. Specifically, we consider a polymer (single strand or star) attached to the tip of a cone, at a separation h from a surface (or another cone). At close proximity, such that h<<R_0, separation is the only remaining relevant scale and the entropic force must take the form F=AkT/h. The amplitude A is universal, and can be related to exponents \eta governing the anomalous scaling of polymer correlations in the presence of obstacles. We use analytical, numerical and epsilon-expansion techniques to compute the exponent \eta for a polymer attached to the tip of the cone (with or without an additional plate or cone) for ideal and self-avoiding polymers. The entropic force is of the order of 0.1 pN at 0.1 micron for a single polymer, and can be increased for a star polymer.Comment: LaTeX, 15 pages, 4 eps figure

Compounding Impacts of Human-Induced Water Stress and Climate Change on Water Availability

The terrestrial phase of the water cycle can be seriously impacted by water management and human water use behavior (e.g., reservoir operation, and irrigation withdrawals). Here we outline a method for assessing water availability in a changing climate, while explicitly considering anthropogenic water demand scenarios and water supply infrastructure designed to cope with climatic extremes. The framework brings a top-down and bottom-up approach to provide localized water assessment based on local water supply infrastructure and projected water demands. When our framework is applied to southeastern Australia we find that, for some combinations of climatic change and water demand, the region could experience water stress similar or worse than the epic Millennium Drought. We show considering only the influence of future climate on water supply, and neglecting future changes in water demand and water storage augmentation might lead to opposing perspectives on future water availability. While human water use can significantly exacerbate climate change impacts on water availability, if managed well, it allows societies to react and adapt to a changing climate. The methodology we present offers a unique avenue for linking climatic and hydrologic processes to water resource supply and demand management and other human interactions