Exploring and Analyzing the Systemic Delivery Barriers for Nanoparticles

Most nanomedicines require efficient in vivo delivery to elicit meaningful diagnostic and therapeutic effects. However, en route to their intended tissues, systemically administered nanoparticles often encounter delivery barriers. To describe these barriers, the term “nanoparticle blood removal pathways” (NBRP) is proposed, which summarizes the interactions between nanoparticles and the body's various cell-dependent and cell-independent blood clearance mechanisms. Nanoparticle design and biological modulation strategies are reviewed to mitigate nanoparticle-NBRP interactions. As these interactions affect nanoparticle delivery, the preclinical literature from 2011–2021 is studied, and the nanoparticle blood circulation and organ biodistribution data are analyzed. The findings reveal that nanoparticle surface chemistry affects the in vivo behavior more than other nanoparticle design parameters. Combinatory biological-PEG surface modification improves the blood area under the curve by ≈418%, with a decrease in liver accumulation of up to 47%. A greater understanding of nanoparticle-NBRP interactions and associated delivery trends will provide new nanoparticle design and biological modulation strategies for safer, more effective, and more efficient nanomedicines.     

Cost minimization and workload balancing in printed circuit board assembly

We consider an operation assignment problem arising from a Printed Circuit (PC) board assembly process. The research was inspired by applications at Hewlett-Packard Company where hundreds of types of PC boards require the insertion of thousands of types of components. The components can be inserted manually or by automated insertion machines. The machines can only hold a limited number of different component types. We investigate how to assign the boards and components to the machines and manual process so as to minimize cost while at the same time balancing machine workloads. We first present a Binary Integer Program (BIP) formulation of the problem. We then develop optimality results that allow us to reduce significantly the size of the BIP. Using the improved BIP formulation, and upper bounds generated using a Cost Minimizing Workload Balancing (CMWB) heuristic that we develop, we show how branch-and-bound can be used to find optimal solutions to small and medium-sized problems in reasonable time. We also show that the CMWB heuristic finds solutions in seconds of CPU time that are within a few percent of optimal. In addition, the CMWB heuristic outperforms the heuristic that has been used at Hewlett-Packard, as well as the longest expected processing time heuristic. Although this paper specifically addresses a problem of partially-automated PC board assembly, the results apply to a more general set of problems, including job and tool assignment in flexible manufacturing systems, and general operation assignment problems.     

Gender differences in adjustment to bereavement: An empirical and theoretical review.

The loss of a marital partner results in substantial increases in morbidity and mortality among both men and women, but the effects are relatively greater for widowers than for widows in the acute grieving period. Evidence is reviewed, and explanations of the pattern are examined. An interpretation in terms of gender differences in social support (M. Stroebe & W. Stroebe, 1983), although plausible, has not yet been empirically confirmed. Likewise, with respect to gender differences in coping styles, women are more confrontive and expressive of their emotions than men, but there has been little validation of the generally accepted grief work hypothesis (working through grief by women brings about their better recovery). Cognitive processes underlying effective coping with bereavement are analyzed, and a stressor-specific framework, the dual process model of coping with loss, is suggested to help explain gender differences in health outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perceiving unfairness in the family: Cause or consequence of marital distress?

[Correction Notice: An erratum for this article was reported in Vol 80(3) of Journal of Personality and Social Psychology (see record 2007-17568-001). The key coefficients on the diagonal paths were incorrect. The corrected figures in their entirety appear in the erratum.] This research tests a model suggesting that marital distress leads individuals to scrutinize of what is given and received in the relationship. This scrutiny elicits perceptions of unfairness that maintain or exacerbate marital distress. In a 3-panel longitudinal study tracking married couples across the transition to parenthood, both wives' and husbands' reports of marital conflict and wives' marital dissatisfaction at Time 1 positively predicted perceived unfairness of the allocation of household tasks at Time 2, controlling for earlier perceptions of unfairness. In addition, there was evidence of perceived unfairness of division of labor at Time 2 predicting marital conflict and marital dissatisfaction for wives at Time 3, controlling for earlier conflict and dissatisfaction. This model of relationship distress and perceptions of unfairness is contrasted with prior interpretations of links between perceived injustice and distress in relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cerebral lateralization and cognitive functioning in patients with congenital adrenal hyperplasia.

A battery of tests was administered to 17 patients with congenital adrenal hyperplasia (CAH) and 17 normal controls to investigate the effect of prenatal androgen exposure on cerebral lateralization and cognitive performance. Individuals were compared on measures of hand preference, verbal and performance IQ, and temporal processing asymmetry. A higher incidence of left-handedness was found among CAH participants. CAH individuals exhibited higher performance IQs as opposed to verbal IQs. Temporal processing asymmetries were investigated using an auditory gap detection task. Measures of reaction time and response error revealed a right-ear, therefore left-hemisphere, advantage for gap detection. This right-ear advantage did not differ between CAH individuals and controls. Results partially support the hypothesis that prenatal androgen exposure causes a shift in cerebral lateralization toward right-hemisphere dominance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Insomnia and the eye of the beholder: Are there clinical markers of objective sleep disturbances among adults with and without insomnia complaints?

Previous findings suggest that some who report insomnia sleep well, whereas some noncomplaining individuals sleep rather poorly. This study was conducted to determine if mood, anxiety, and sleep-related beliefs might relate to perceived sleep disturbance. Thirty-two women and 32 men (aged 40–79 years) with primary insomnia and an aged-matched sample of 61 normal sleepers (31 women, 30 men) completed 6 nocturnal sleep recordings, as well as the Beck Depression Inventory (BDI), the Trait portion of the State-Trait Anxiety Inventory (STAI-2), and the Dysfunctional Beliefs and Attitudes About Sleep Questionnaire. Sleep and interview data were used to subdivide the majority of the sample (n?=?108) into objective normal sleepers and subjective insomnia sufferers who seemingly slept well and subjective normal sleepers and objective insomnia sufferers who slept poorly. The 2 subjective subgroups showed the most marked differences on most of the psychometric measures. The findings suggest that the psychological factors scrutinized in this study may mediate sleep satisfaction and/or predict objective sleep difficulties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preparation and characterization of hollow microcapsules for use as ultrasound contrast agents

A laboratory-scale method of producing micron-sized hollow microscapsules from a biodegradable polymer such as 50/50 poly(D, L-lactide-co-glycolide) (PLGA), for use as a diagnostic ultrasound contrast agent, was developed. The technique involved microencapsulation of a volatile solid core material, and subsequent sublimation of the core to leave a hollow microsphere. A core material, such as ammonium carbonate, was ground to a suitable size distribution and encapsulated by a modified solvent evaporation or coacervation technique. This study investigated process parameters to produce diagnostically viable microscapsules by these two en-capsulation methods, such as polymer molecular weight (from 10,000 to 50,000), initial polymer concentration, agitation method, and stabilizer type. Polymer solution viscosity, polydispersity, and agitation rates significantly controlled the mean size of the microcapsules. Stabilizers were essential in solvent evaporation, but corrupted the morphology of spheres made by coacervation. Zeta potential values of microsphere dispersions revealed differences in surface characteristics between both encapsulation methods. Incubation of microcapsules with serum improved their dispersion in aqueous media. Preliminary in vivo ultrasound studies with the New Zealand white rabbit model, using color Doppler, showed that the microcapsules gave significant contrast in the right kidney.     

Electrical and Mechanical Self‐Healing in High‐Performance Dielectric Elastomer Actuator Materials

Dielectric elastomers are of interest for actuator applications due to their large actuation strain, high bandwidth, high energy density, and their flexible nature. If future dielectric elastomers are to be used reliably in applications that include soft robotics, medical devices, artificial muscles, and electronic skins, there is a need to design devices that are tolerant to electrical and mechanical damage. In this paper, the first report of self‐healing of both electrical breakdown and mechanical damage in dielectric actuators using a thermoplastic methyl thioglycolate–modified styrene–butadiene–styrene (MGSBS) elastomer is provided. The self‐healing functions are examined from the material to device level by detailed examination of the healing process, and characterization of electrical properties and actuator response before and after healing. It is demonstrated that after dielectric breakdown, the initial dielectric strength can be recovered by up to 67%, and after mechanical damage, a 39% recovery can be achieved with no degradation of the strain–voltage response of the actuators. The elastomer can also heal a combination of mechanical and electrical failures. This work provides a route to create robust and damage tolerant dielectric elastomers for soft robotic and other applications related to actuator and energy‐harvesting systems.     

Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in > 50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of ODAD1 (CCDC114), a component of the outer dynein arm docking complex, results in a failure to assemble outer dynein arms (ODAs), mostly immotile cilia, and a typical PCD phenotype. We identified a female (now 34 years old) with an unusually mild clinical phenotype who has a homozygous non-canonical splice mutation (c.1502+5G>A) in ODAD1. To investigate the mechanism for the unusual phenotype, we performed molecular and functional studies of cultured nasal epithelial cells. We demonstrate that this splice mutation results in the expression of a truncated protein that is attached to the axoneme, indicating that the mutant protein retains partial function. This allows for the assembly of some ODAs and a significant level of ciliary activity that may result in the atypically mild clinical phenotype. The results also suggest that partial restoration of ciliary function by therapeutic agents could lead to significant improvement of disease symptoms.