Measurement of immunotargeted plasmonic nanoparticles' cellular binding: a key factor in optimizing diagnostic efficacy

In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates.     

Influence of fiber optic probe geometry on the applicability of inverse models of tissue reflectance spectroscopy: computational models and experimental measurements

Accurate recovery of tissue optical properties from in vivo spectral measurements is crucial for improving the clinical utility of optical spectroscopic techniques. The performance of inversion algorithms can be optimized for the specific fiber optic probe illumination-collection geometry. A diffusion-theory-based inversion method has been developed for the extraction of tissue optical properties from the shape of normalized tissue diffusion reflectance spectra, specifically tuned for a fiber probe that comprises seven hexagonally close-packed fibers. The central fiber of the probe goes to the spectrometer as the detecting fiber, and the surrounding six outer fibers are connected to the white-light source as illumination fibers. The accuracy of the diffusion-based inversion algorithm has been systematically assessed against Monte Carlo (MC) simulation as a function of probe geometry and tissue optical property combinations. By use of this algorithm, the spectral absorption and scattering coefficients of normal and cancerous tissue are efficiently retrieved. Although there are significant differences between the diffusion approximation and the MC simulation at short source-detector (SD) separations, we show that with our algorithm the tissue optical properties are well retrieved within the SD separation of 0.5-3 mm that is compatible with endoscopic specifications. The presented inversion method is computationally efficient for eventual real-time in vivo tissue diagnostics application.     

Prospective memory in an air traffic control simulation: External aids that signal when to act.

At work and in our personal life we often need to remember to perform intended actions at some point in the future, referred to as Prospective Memory. Individuals sometimes forget to perform intentions in safety-critical work contexts. Holding intentions can also interfere with ongoing tasks. We applied theories and methods from the experimental literature to test the effectiveness of external aids in reducing prospective memory error and costs to ongoing tasks in an air traffic control simulation. Participants were trained to accept and hand-off aircraft and to detect aircraft conflicts. For the prospective memory task, participants were required to substitute alternative actions for routine actions when accepting target aircraft. Across two experiments, external display aids were provided that presented the details of target aircraft and associated intended actions. We predicted that aids would only be effective if they provided information that was diagnostic of target occurrence, and in this study, we examined the utility of aids that directly cued participants when to allocate attention to the prospective memory task. When aids were set to flash when the prospective memory target aircraft needed to be accepted, prospective memory error and costs to ongoing tasks of aircraft acceptance and conflict detection were reduced. In contrast, aids that did not alert participants specifically when the target aircraft were present provided no advantage compared to when no aids were used. These findings have practical implications for the potential relative utility of automated external aids for occupations where individuals monitor multi-item dynamic displays. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The real relationship in psychotherapy: Relationships to adult attachments, working alliance, transference, and therapy outcome.

The purpose of this study was to understand how the real relationship (RR) relates to important process and outcome variables from both the clients’ and therapists’ perspectives. Using a sample of 31 therapist/client dyads at a university counseling center, the authors examined the RR at the 3rd session of therapy and at termination. The results revealed that client adult attachment avoidance was negatively correlated with client RR, while client adult attachment anxiety was uncorrelated. Therapists’ ratings of negative transference were negatively correlated with therapist-rated RR and were uncorrelated with client-rated RR. Hierarchical linear modeling analyses were conducted to predict postintervention outcome from client and therapist perceptions of the RR. Therapists’ ratings of the RR accounted for a significant amount of variance in client posttreatment symptoms while controlling pretreatment symptoms. Client-rated RR total scores and client and therapist 3rd-session alliance scores were not significant predictors of postsymptom ratings. Implications of the usefulness of measuring the RR in psychotherapy are discussed, as are recommendations for future study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cognitive processes underlying event-based prospective memory in school-age children and young adults: A formal model-based study.

Fifty children 7 years of age (29 girls, 21 boys), 53 children 10 years of age (29 girls, 24 boys), and 36 young adults (19 women, 17 men) performed a computerized event-based prospective memory task. All 3 groups differed significantly in prospective memory performance, with adults showing the best performance and with 7-year-olds showing the poorest performance. We used a formal multinomial process tree model of event-based prospective memory to decompose age differences in cognitive processes that jointly contribute to prospective memory performance. The formal modeling results demonstrate that adults differed significantly from the 7-year-olds and the 10-year-olds on both the prospective component and the retrospective component of the task. The 7-year-olds and the 10-year-olds differed only in the ability to recognize prospective memory target events. The prospective memory task imposed a cost to ongoing activities in all 3 age groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploring Work and Family Distractions: Antecedents and Outcomes.

Drawing from expansionist theory and time-based role-conflict theory, this research investigated antecedents and outcomes of time spent in 1 role while distracted or preoccupied by another role. Survey data from a sample of 171 working mothers generally supported hypotheses linking work and family distractions to role quality. Work-role overload was positively related to work distractions experienced at home, and traditional gender-role expectations were positively related to family distractions experienced at work. In terms of outcomes, work distractions at home were negatively related to job satisfaction. Results illustrate the importance of role quality and the efficacy of alternate operationalizations of role time in the effort to better understand the interface between work and family. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cost of event-based prospective memory: Salient target events.

Evidence has begun to accumulate showing that successful performance of event-based prospective memory (PM) comes at a cost to other ongoing activities. The current study builds on previous work by examining the cost associated with PM when the target event is salient. Target salience is among the criteria for automatic retrieval of intentions according to the multiprocess view of PM. An alternative theory, the preparatory attentional and memory processes theory, argues that PM performance, including retrieval of the intent, is never automatic and successful performance always will come at a cost to other ongoing activity. The 4 experiments reported here used a salient PM target event. In addition, Experiments 3 and 4 were designed to meet the stringent criteria proposed for automatic retrieval of intentions by multiprocess theory, and, yet, in all 4 experiments, delayed intentions interfered with ongoing task performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scanning electrochemical microscopy of model neurons: imaging and real-time detection of morphological changes

Living PC12 cells, a model cell type for studying neuronal function, were imaged using the negative feedback mode of a scanning electrochemical microscope (SECM). Six biocompatible redox mediators were successfully identified from a large pool of candidates and were then used for imaging PC12 cells before and after exposure to nerve growth factor (NGF). When exposed to NGF, cells differentiate into a neuron phenotype by growing narrow neurites (1-2 microm wide) that can extend > 100 microm from the cell proper. We demonstrate that carbon fiber electrodes with reduced tip diameters can be used for imaging both the cell proper and these neurites. Regions of decreased current, possibly resulting from raised features not identifiable by light microscopy, are clearly evident in the SECM images. Changes in the morphology of undifferentiated PC12 cells could be detected in real time with the SECM. After exposure to hypotonic and hypertonic solutions, reversible changes in cell height of <2 microm were measured.     

Rheological properties of yeasted and nonyeasted wheat doughs developed under different mixing conditions

BACKGROUND: In order to explore the differences in rheological behaviour of full formula and flour/water doughs due to mixing, small‐amplitude oscillatory strain (SAOS) rheological measurements were made on fully developed nonyeasted and inactivated yeasted dough formulations mixed at various speeds using the Brabender Farinograph and the Bohlin ReoMixer. These results were compared with large‐strain empirical rheological results (including Kieffer rig uniaxial extension) as well as baking test results to determine differences due to mixer speed and/or flow distribution. RESULTS: The uniaxial extension and baking tests detected mixing speeds with incomplete dough development. Above those speeds, energy input to peak development was relatively constant in the Farinograph. Extensibility trends showed increases with speed in the yeasted dough samples, which were attributed to variation in fermentation time during mixing to peak torque at different speeds. While SAOS results did not show differences due to mixing speed, they did detect differences between the yeasted and nonyeasted dough formulations, as well as significant differences (P < 0.01) between yeasted doughs mixed in the two different mixers. CONCLUSION: The results indicate that known differences in the distribution of elongational and shear flows in the two mixers impact the development of dough structure during mixing. Copyright © 2008 Society of Chemical Industry