Luminescent amphiphilic nanogels by terpyridine-Zn(II) complexation of polymeric micelles

In this work, we investigated terpyridine (tpy)/Zn(II) complexation for the crosslinking of polymeric micelles of the branched poly(ethylene oxide)–poly(propylene oxide) block copolymer Tetronic® 1107 (T1107) in water and produce physically stable amphiphilic luminescent nanogels. Nanoparticles displayed a size of 235 ± 25 and 318 ± 57 nm before and after Zn(II) crosslinking, respectively, as measured by dynamic light scattering. High-resolution scanning electron microscopy analysis revealed the multimicellar nature of the crosslinked nanoparticles. In addition, Zn(II) complexation prevented nanoparticle disassembly after extreme dilution below the critical micellar concentration and reduced the minimum concentration required for the reverse thermal gelation of concentrated aqueous T1107 systems. The cell compatibility and uptake were initially assessed in the murine macrophage cell line RAW 264.7. Results showed that complexation increases the cell compatibility of the nanoparticles with respect to the non-complexed counterparts. In addition, non-crosslinked nanoparticles accumulated in the cell membrane, while the complexed ones were internalized, as observed by confocal laser scanning fluorescence microscopy. Then, the antiproliferative activity of the crosslinked nanoparticles was confirmed in the rhabdomyosarcoma cell line Rh30; their inhibitory concentration 50 (IC₅₀) being 101 μg/mL (6.7 μM). Finally, the encapsulation and release of the hydrophobic antiretroviral efavirenz was characterized in vitro. Complexation slightly reduced the release kinetics with respect to the pristine nanoparticles. Overall results demonstrate the promise of this simple modification strategy to produce amphiphilic nanogels with a set of advantageous physicochemical, optical, and biological properties.     

Quantifying the value of buyer–vendor coordination: Analytical and numerical results under different replenishment cost structures

Despite a growing interest in channel coordination, no detailed analytical or numerical results measuring its impact on system performance have been reported in the literature. Hence, this paper aims to develop analytical and numerical results documenting the system-wide cost improvement rates that are due to coordination. To this end, we revisit the classical buyer–vendor coordination problem introduced by Goyal [S.K. Goyal, An integrated inventory model for a single-supplier single-customer problem. International Journal of Production Research 15 (1976) 107–111] and extended by Toptal et al. [A. Toptal, S. Çetinkaya, C.-Y. Lee, The buyer–vendor coordination problem: modeling inbound and outbound cargo capacity and costs, IIE Transactions on Logistics and Scheduling 35 (2003) 987–1002] to consider generalized replenishment costs under centralized decision making. We analyze (i) how the counterpart centralized and decentralized solutions differ from each other, (ii) under what circumstances their implications are similar, and (iii) the effect of generalized replenishment costs on the system-wide cost improvement rates that are due to coordination. First, considering Goyal’s basic setting, we show that the improvement rate depends on cost parameters. We characterize this dependency analytically, develop analytical bounds on the improvement rate, and identify the problem instances in which considerable savings can be achieved through coordination. Next, we analyze Toptal et al.’s [A. Toptal, S. Çetinkaya, C.-Y. Lee, The buyer–vendor coordination problem: modeling inbound and outbound cargo capacity and costs, IIE Transactions on Logistics and Scheduling 35 (2003) 987–1002] extended setting that considers generalized replenishment costs representing inbound and outbound transportation considerations, and we present detailed numerical results quantifying the value of coordination. We report significant improvement rates with and without explicit transportation considerations, and we present numerical evidence which suggests that larger rates are more likely in the former case.     

Escape Through a Small Opening: Receptor Trafficking in a Synaptic Membrane

We model the motion of a receptor on the membrane surface of a synapse as free Brownian motion in a planar domain with intermittent trappings in and escapes out of corrals with narrow openings. We compute the mean confinement time of the Brownian particle in the asymptotic limit of a narrow opening and calculate the probability to exit through a given small opening, when the boundary contains more than one. Using this approach, it is possible to describe the Brownian motion of a random particle in an environment containing domains with small openings by a coarse grained diffusion process. We use the results to estimate the confinement time as a function of the parameters and also the time it takes for a diffusing receptor to be anchored at its final destination on the postsynaptic membrane, after it is inserted in the membrane. This approach provides a framework for the theoretical study of receptor trafficking on membranes. This process underlies synaptic plasticity, which relates to learning and memory. In particular, it is believed that the memory state in the brain is stored primarily in the pattern of synaptic weight values, which are controlled by neuronal activity. At a molecular level, the synaptic weight is determined by the number and properties of protein channels (receptors) on the synapse. The synaptic receptors are trafficked in and out of synapses by a diffusion process. Following their synthesis in the endoplasmic reticulum, receptors are trafficked to their postsynaptic sites on dendrites and axons. In this model the receptors are first inserted into the extrasynaptic plasma membrane and then random walk in and out of corrals through narrow openings on their way to their final destination.     

An integrated model for screening cargo containers

This paper focuses on detecting nuclear weapons on cargo containers using port security screening methods, where the nuclear weapons would presumably be used to attack a target within the United States. This paper provides a linear programming model that simultaneously identifies optimal primary and secondary screening policies in a prescreening-based paradigm, where incoming cargo containers are classified according to their perceived risk. The proposed linear programming model determines how to utilize primary and secondary screening resources in a cargo container screening system given a screening budget, prescreening classifications, and different device costs. Structural properties of the model are examined to shed light on the optimal screening policies. The model is illustrated with a computational example. Sensitivity analysis is performed on the ability of the prescreening in correctly identifying prescreening classifications and secondary screening costs. Results reveal that there are fewer practical differences between the screening policies of the prescreening groups when prescreening is inaccurate. Moreover, devices that can better detect shielded nuclear material have the potential to substantially improve the system’s detection capabilities.     

活细胞中的化学物理-光学观测和控制细胞内信号转导

Cells are crowded microenvironments filled with macromolecules undergoing constant physical and chemical interactions. The physicochemical makeup of the cells affects various cellular responses, determines cell-cell interactions and influences cell decisions. Chemical and physical properties differ between cells and within cells. Moreover, these properties are subject to dynamic changes in response to environmental signals, which often demand adjustments in the chemical or physical states of intracellular molecules. Indeed, cellular responses such as gene expression rely on the faithful relay of information from the outside to the inside of the cell, a process termed signal transduction. The signal often traverses a complex path across subcellular spaces with variable physical chemistry, sometimes even influencing it. Understanding the molecular states of such signaling molecules and their intracellular environments is vital to our understanding of the cell. Exploring such intricate spaces is possible today largely because of experimental and theoretical tools. Here, we focus on one tool that is commonly used in chemical physics studies-light. We summarize recent work which uses light to both visualize the cellular environment and also control intracellular processes along the axis of signal transduction. We highlight recent accomplishments in optical microscopy and optogenetics, an emerging experimental strategy which utilizes light to control the molecular processes in live cells. We believe that optogenetics lends unprecedented spatiotemporal precision to the manipulation of physicochemical properties in biological contexts. We hope to use this work to demonstrate new opportunities for chemical physicists who are interested in pursuing biological and biomedical questions.     

A dual-response forwarding approach for containerizing air cargoes under uncertainty,based on stochastic mixed 0-1 programming

This paper proposes a dual-response forwarding approach for renting air containers and simultaneously determining how cargoes are distributed into the containers under uncertain information. Containers have to be booked in advance to obtain a discount rental rate from airlines, as urgent requirement or cancellation of containers on the day of shipping will incur a heavy penalty. We firstly formulate a mixed 0-1 integer model to determine the booking types and quantities of containers for the deterministic problem under accurate information. We then formulate a stochastic mixed 0-1 model to structure a dual-response forwarding system for the uncertain problem where accurate information is not available when booking. The first-stage response is to determine the booking types and quantities of containers. The second-stage response is to prepare for different scenarios that might occur on the day of shipping, including the types and quantities of containers required or returned for each scenario, and also the corresponding cargo loading plan. Computational results show that the stochastic model can provide a cost-efficient, flexible and responsive cargo forwarding system.     

Chemical Physics in Living Cells-using Light to Visualize and Control Intracellular Signal Transduction?

Cells are crowded microenvironments filled with macromolecules undergoing constant physical and chemical interactions. The physicochemical makeup of the cells affects various cellular responses, determines cell-cell interactions and influences cell decisions. Chemical and physical properties differ between cells and within cells. Moreover, these properties are subject to dynamic changes in response to environmental signals, which often demand adjustments in the chemical or physical states of intracellular molecules. Indeed, cellular responses such as gene expression rely on the faithful relay of information from the outside to the inside of the cell, a process termed signal transduction. The signal often traverses a complex path across subcellular spaces with variable physical chemistry, sometimes even influencing it. Understanding the molecular states of such signaling molecules and their intracellular environments is vital to our understanding of the cell. Exploring such intricate spaces is possible today largely because of experimental and theoretical tools. Here, we focus on one tool that is commonly used in chemical physics studies-light. We summarize recent work which uses light to both visualize the cellular environment and also control intracellular processes along the axis of signal transduction. We highlight recent accomplishments in optical microscopy and optogenetics, an emerging experimental strategy which utilizes light to control the molecular processes in live cells. We believe that optogenetics lends unprecedented spatiotemporal precision to the manipulation of physicochemical properties in biological contexts. We hope to use this work to demonstrate new opportunities for chemical physicists who are interested in pursuing biological and biomedical questions.     

Cellular Uptake,Intracellular Trafficking and Biological Responses of Gold Nanoparticles

Promising application of gold nanoparticles (GNPs) in biomedical and environmental fields is increasing the likelihood of direct interaction with living systems. The knowledge about GNPs interacting with cells is quite limited and however, is necessary for risk prediction and evaluation of biological effects. Herein, we review recent advances in cellular effects of GNPs including cellular uptake, trafficking, subcellular distribution and cellular responses, and the relationship between physiochemical properties of GNPs and biological effects as well. To uncover these issues, it is quite instructive for safe and sustainable use of GNPs.     

A compromised large-scale neighborhood search heuristic for capacitated air cargo loading planning

Cost effectiveness is central to the air freight forwarders. In this work, we study how an air freight forwarder should plan its cargo loading in order to minimize the total freight cost given a limited number of rented containers. To solve the problem efficiently for practical implementation, we propose a new large-scale neighborhood search heuristic. The proposed large-scale neighborhood relaxes the subset-disjoint restriction made in the existing literature; the relaxation risks a possibility of infeasible exchanges while at the same time it avoids the potentially large amount of checking effort required to enforce the subset-disjoint restriction. An efficient procedure is then used to search for improvement in the neighborhood. We have also proposed a subproblem to address the difficulties caused by the fixed charges. The compromised large-scale neighborhood (CLSN) search heuristic has shown stably superior performance when compared with the traditional large-scale neighborhood search and the mixed integer programming model.     

Colocalizing ribozymes with substrate rnas to increase their efficacy as gene inhibitors

The ability to target ribozymes to specifically cleave viral RNAs in vitro has led to much speculation about their potential therapeutic value as antiviral agents in vivo. To transfer a ribozyme’s potential as an antiviral agent from test tubes to cells and organisms successfully, the characteristics that distinguish these settings must be considered. In vitro, ribozymes and substrate RNAs freely diffuse in solution in test tubes, and trans-cleavage reactions are dependent on a diffusive step. In eukaryotic cells, by contrast, many RNAs do not appear to diffuse freely. Instead, they appear to be highly compartmentalized and actively sorted to specific cellular locations. Such RNA trafficking may result in localization of substrate RNAs in a different compartment than ribozymes, which would effectively reduce substrate RNA availability to ribozymes and therefore limit the effectiveness of ribozymes as gene inhibitors.