Removal of the phosphate group in mechanism-based inhibitors of inositol monophosphatase leads to unusual inhibitory activity

Inositol monophosphatase is widely held to be the therapeutic target for inhibition by lithium ion in the treatment of bipolar disorder. In a continued effort to improve the bioavailability of alternative inhibitors, we have designed and tested two new series of compounds; phosphonates and product-like mimics. Phosphonate substrate mimics were competitive inhibitors of reduced potency as compared to phosphate based inhibitors. Product mimics however, showed various inhibitory modes of action. The 6-butylamino derivative 6p was an uncompetitive inhibitor when acting alone (K(i)= 0.3 mM) but displayed non-competitive inhibition in the presence of inorganic phosphate. This compound represents a new lead in the search for a viable replacement for lithium ion therapy.     

On the use of sensitivity analysis in model reduction to predict flows for varying inflow conditions

The proper orthogonal decomposition (POD)‐based model reduction method is more and more successfully used in fluid flows. However, the main drawback of this methodology rests in the robustness of these reduced order models (ROMs) beyond the reference at which POD modes have been derived. Any variation in the flow or shape parameters within the ROM fails to predict the correct dynamics of the flow field. To broaden the spectrum of these models, the POD modes should have the global characteristics of the flow field over which the predictions are required. Mixing of snapshots with varying parameters is one way to improve the global nature of the modes but is computationally demanding because it requires full‐order solutions for a number of parameter values in order to assemble atextitrich enough database on which to perform POD. Instead, we have used sensitivity analysis (SA) to include the flow and shape parameters influence during the basis selection process to develop more robust ROMs for varying viscosity (Reynolds number), changing orientation and shape definition of bodies. This study aims at extending these ideas to inflow conditions to demonstrate the effectiveness of the proposed approach in capturing the effect of varying inflow on the dynamics of the flow over an elliptic cylinder. Numerical experiments show that the newly derived models allow for a more accurate representation of the flows when exploring the parameter space. Copyright © 2011 John Wiley & Sons, Ltd.     

Hybrid anion exchange membrane of hydroxyl-modified polysulfone incorporating guanidinium-functionalized graphene oxide

Incorporating nanofillers is an effective method to balance conductivity and mechanical strength of anion exchange membranes (AEMs). In this work, a series of AEMs were prepared via embedding guanidinium-functionalized graphene oxide (GGO) into un-quaternized, diethanolamine-modified polysulfone (HPSf). The improved hydrophilicity of HPSf allows for better compatibility between GGO and polymer and also gives higher water uptake, which is beneficial for facilitating ion transport and alleviating hydroxide attack. AEM of HPSf embedding an optimized amount of GGO (0.88 mmol g^?1) exhibits the highest conductivity of 11 mS cm^?1 at 30 °C, which is 38% higher than that of pristine PSf-GGO membrane. It also possesses excellent anti-swelling stability (9% swelling ratio at 60 °C). When treated with 1 M NaOH at 60 °C for 120 h, HPSf-GGO-25% experienced a conductivity decay by 25%. Our work provides a route to fabrication of hybrid AEMs with improved interface properties and well-balanced conductivity and robustness.     

Crime hotspot prediction based on dynamic spatial analysis

Crime is not a completely random event but rather shows a pattern in space and time. Capturing the dynamic nature of crime patterns is a challenging task. Crime prediction models that rely only on neighborhood influence and demographic features might not be able to capture the dynamics of crime patterns, as demographic data collection does not occur frequently and is static. This work proposes a novel approach for crime count and hotspot prediction to capture the dynamic nature of crime patterns using taxi data along with historical crime and demographic data. The proposed approach predicts crime events in spatial units and classifies each of them into a hotspot category based on the number of crime events. Four models are proposed, which consider different covariates to select a set of independent variables. The experimental results show that the proposed combined subset model (CSM), in which static and dynamic aspects of crime are combined by employing the taxi dataset, is more accurate than the other models presented in this study.     

Flow Properties of Moderately Concentrated Solutions of Cellulose Acetate Polymer

Calculations [1] of rheological properties of polymeric solutions have usually been restricted to very dilute o r to very concentrated solutions. In either case, one starts with a model for the micro- structure. Between these two conceptual extremes lies the broad class of moderately concentrated solutions. To cover this region theoretically, two approaches have been used; 1) network theories focusing attention on entanglement junctions, and 2) single-molecule theories focusing attention on single molecules but including inter- molecular interactions. Williams, Wang, and Zimm introduced a double model; one for a particular macromolecule and another for solutions containing like molecules in which the chosen macro- molecule is suspended. This approach has turned out to be quite successful because spheres immersed in a suspension of like spheres behave as i f suspended in a Newtonian fluid, and the resulting ex- pression for viscosity is quite simple in form and qualitatively correct for moderate concentrations.     

Joint routing,link capacity dimensioning,and switch port optimization for dynamic traffic in optical networks

This paper considers a challenging problem: to simultaneously optimize the cost and the quality of service in opaque wavelength division multiplexing (WDM) networks. An optimization problem is proposed that takes the information including network topology, traffic between end nodes, and the target level of congestion at each link/node in WDM networks. The outputs of this problem include routing, link channel capacities, and the optimum number of switch ports locally added/dropped at all switch nodes. The total network cost is reduced to maintain a minimum congestion level on all links, which provides an efficient trade-off solution for the network design problem. The optimal information is utilized for dynamic traffic in WDM networks, which is shown to achieve the desired performance with the guaranteed quality of service in different networks. It was found that for an average link blocking probability equal to 0.015, the proposed model achieves a net channel gain in terms of wavelength channels ( ) equal to 35.72 , 39.09 , and 36.93 compared to shortest path first routing and equal to 29.41 , 37.35 , and 27.47 compared to alternate routing in three different networks.     

Plant‐supported silver nanoparticles: Efficient,economically viable and easily recoverable catalyst for the reduction of organic pollutants

Ginger rhizome powder was used for the synthesis of supported metallic nanoparticle catalysts. A simple and novel adsorption method was used for the synthesis of silver nanoparticles loaded on ginger powder (Ag/GP), copper on ginger powder (Cu/GP) and nickel on ginger powder (Ni/GP). Among these, Ag/GP showed selective reduction of methyl orange and was used for further reactions. The prepared nanomaterials were characterized through X‐ray diffraction, transmission electron microscopy, field emission scanning electron microscopy, fourier transform infrared spectroscopy and energy‐dispersive X‐ray spectroscopy. The prepared Ag/GP catalyst was employed in the catalytic reduction of 4‐nitrophenol (4‐NP), 2‐nitrophenol (2‐NP), rhodamine B, methyl red and congo red. Ag/GP showed excellent catalytic reduction activity, the rate constants being 1.26 × 10^?3 and 2.38 × 10^?3 s^?1 for 2‐NP and 4‐NP, respectively. The turnover frequency reached 1.06 min^?1 for 2‐NP and 1.16 min^?1 for 4‐NP when using the Ag/GP catalyst. The prepared Ag/GP catalyst demonstrated outstanding activity for the degradation of a mixed solution of dyes. Also, stability and reusability of the prepared catalyst were investigated, which showed outstanding reusability up to five times and was stable up to five days.     

A multi-dimensional crime spatial pattern analysis and prediction model based on classification

This article presents a multi-dimensional spatial pattern analysis of crime events in San Francisco. Our analysis includes the impact of spatial resolution on hotspot identification, temporal effects in crime spatial patterns, and relationships between various crime categories. In this work, crime prediction is viewed as a classification problem. When predictions for a particular category are made, a binary classification-based model is framed, and when all categories are considered for analysis, a multiclass model is formulated. The proposed crime-prediction model (HotBlock) utilizes spatiotemporal analysis for predicting crime in a fixed spatial region over a period of time. It is robust under variation of model parameters. HotBlock's results are compared with baseline real-world crime datasets. It is found that the proposed model outperforms the standard DeepCrime model in most cases.