Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

Clinical evaluation of technetium-99m-L,L-ethylenedicysteine in patients with chronic renal failure

1. Effects of feeding condition from birth were examined on the sensitivity of neuromuscular transmission to d-tubocurarine (dTc) in vitro in male mice of the ddY strain. 2. Mice were trained to climb two separated cylindrical steel-wire tubes for feeding and drinking, respectively, from 16 days of age. Some mice were conventionally fed, from 99 days of age. Nerve-muscle preparations were made from the left phrenic nerve diaphragm muscle (DPH), the sciatic nerve soleus muscle (SOL), and the sciatic nerve extensor digitorum longus muscle (EDL) of 99-day-old and 155-day-old mice. The nerve trunk was electrically activated with trains of four pulses and tetanic pulses. 3. The sensitivity to the effects of dTc decreased in the order EDL, SOL, and DPH. This result held true in all mice tested. 4. This sensitivity was significantly potentiated by the compulsory movement. 5. The supersensitivity remained even when mice were conventionally fed after 99 days of age. 6. The compulsion rendered EDL antifatigable on tetanic stimulation. This property was also retained after a return to conventional feeding. 7. These results suggest that the effects of feeding condition from birth might remain on neuromuscular functions after termination of the conditioning.     

Short cue presentations encourage advance task preparation: A recipe to diminish the residual switch cost.

In the task-switching literature, it has frequently been demonstrated that although advance task preparation reduces the switch cost, it never really eliminates the switch cost. This remaining residual switch cost received much attention, and it has been argued that advance preparation is restricted in nature. In the present study, the role of task-cue presentation in the establishment of the residual switch cost was investigated. In 4 experiments, the cue was removed during the preparation interval, and it was hypothesized that this would encourage participants to complete advance task preparation. The results of all 4 experiments provided support for this hypothesis: When the cue was presented for a short time and then removed, the residual switch cost completely disappeared. This was found for different cue types. Furthermore, Experiment 3 demonstrated that it was not the presence of the cue itself but merely differences in advance task preparation that caused the effects. This suggests that advance task preparation is not as restricted in nature as previously assumed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The impact of CHP generation on CO2 emissions

The combined generation of heat and power (cogeneration) is praised by many as a technique for reducing the emissions of CO₂ in industrialized nations. This is generally true but not always. In this article we discuss the impact of some major variables on the CO₂ emission reduction capacity of cogeneration. Two sets of variables are predominant: the characteristics of the CHP process and the composition of the electricity generation sector. We highlight the interaction between the two sets of variables with the help of diagrams.     

Differential Display of Investigative Behavior Permits Discrimination of Scent Signatures from Familiar and Unfamiliar Socially Dominant Female Marmoset Monkeys (Callithrix jacchus)

The hypothesis was tested that marmosets have differential displays of investigatory behavior towards circumgenital scent marks from socially dominant females based on degree of familiarity. In a series of two-choice behavioral discrimination bioassays, dominant males together with subordinate and dominant females were presented concurrently with scent secretions from familiar versus unfamiliar dominant females, and their investigative behaviors towards the scent were recorded. Test animals directed significantly different amounts of investigative behaviors towards familiar versus unfamiliar scents when the scent stimuli involved complete circumgenital scent marks, glandular secretion only, or urine only. When animals discriminated between the two scent samples, they did so by directing significantly increased amounts of behavior to scent from unfamiliar females. Chemical cues promoting differential displays of behavior to familiar versus unfamiliar scents appeared to be volatile in nature and were effective in the scent mark for at least one day following deposition. The reliable ability of marmosets to consistently discriminate between odors from familiar versus unfamiliar dominant females provides strong circumstantial evidence that individual female marmosets have distinct chemical signatures. The ability of marmosets to discriminate the odor from familiar versus unfamiliar dominant females may be important in the context of intergroup relations.     

Is cheating a human function? The roles of presence,state hostility,and enjoyment in an unfair video game

In sports and board games, when an opponent cheats, the other players typically greet it with disdain, anger, and disengagement. However, work has yet to fully address the role of the computer cheating in video games. In this study, participants played either a cheating or a non-cheating version of a modified open-source tower-defense game. Results indicate that when a computer competitor cheats, players perceive the opponent as being more human. Cheating also increases player aggravation and presence, but does not affect enjoyment of the experience. Additionally, players that firmly believed that their opponent was controlled by the computer exhibited significantly less state hostility compared to players that were less certain of the nature of their competitor. Game designers can integrate subtle levels of cheating into computer opponents without any real negative responses from the players. The results indicate that minor levels of cheating might also increase player engagement with video games.     

A Quality Software Process for Rapid Application Development

Software organizations can significantly improve the quality of their output if they have a defined and documented software process, together with the appropriate techniques and tools to measure its effectiveness. Without a defined process it is impossible to measure success or focus on how development capability can be enhanced. To date, a number of software process improvement frameworks have been developed and implemented. However, most of these models have been targeted at large-scale producers. Furthermore, they have applied to companies who use traditional development techniques. Smaller companies and those operating in development areas where speed of delivery is paramount have not, as yet, had process improvement paradigms available for adoption.This study examined the software process in a small company and emerged with the recommendation of the use of the Dynamic Systems Development Method (DSDM) and the Personal Software Process (PSP) for achieving software process improvement.     

Effective optimization for fuzzy model predictive control

This paper addresses the optimization in fuzzy model predictive control. When the prediction model is a nonlinear fuzzy model, nonconvex, time-consuming optimization is necessary, with no guarantee of finding an optimal solution. A possible way around this problem is to linearize the fuzzy model at the current operating point and use linear predictive control (i.e., quadratic programming). For long-range predictive control, however, the influence of the linearization error may significantly deteriorate the performance. In our approach, this is remedied by linearizing the fuzzy model along the predicted input and output trajectories. One can further improve the model prediction by iteratively applying the optimized control sequence to the fuzzy model and linearizing along the so obtained simulated trajectories. Four different methods for the construction of the optimization problem are proposed, making difference between the cases when a single linear model or a set of linear models are used. By choosing an appropriate method, the user can achieve a desired tradeoff between the control performance and the computational load. The proposed techniques have been tested and evaluated using two simulated industrial benchmarks: pH control in a continuous stirred tank reactor and a high-purity distillation column.     

Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity.