The surrogate scaffold method for quantifying molecular release kinetics from drug delivery systems

The accurate determination of kinetics of therapeutic release from drug delivery vehicles is an essential step in the optimized design of such systems for biomedical and pharmaceutical applications. Most methods in current use for quantifying therapeutic release rates are developed to provide consistency, reproducibility, and ease of usage in a laboratory setting. These methods, however, do not necessarily mirror the release conditions when the drug delivery system comes into contact with the target tissue environment during application. As a result, the findings from these studies provide only comparative guidelines about the drug delivery rates and duration. Successful optimization of a drug delivery system requires complete, and accurate, knowledge about the release profile over an extended period of time to determine the initial release rate—including burst release if present, the rate of change of the release kinetics, and the maximum duration of delivery at a minimum therapeutic concentration level. We have developed an indirect method for the quantification of release kinetics suitable for nanoparticle-based drug delivery systems that utilizes a hydrogel scaffold as a tissue surrogate to better emulate therapeutic delivery into a target tissue environment. Details of the method and its application to the release of an angiogenic peptide from a nanoparticle emulsion are provided in this communication.     

Fe(III)-humate complexes from Megalopolis peaty lignite: A novel eco-friendly fertilizer

Fe(III)-humate complexes were synthesized from Greek peaty lignite of the Megalopolis Basin. The preparation was carried out under mild and low-energy conditions producing a biodegradable, eco-friendly and effective material to substitute the synthetic chelates Fe-EDDHA, Fe-EDTA and Fe-DTPA. Due to both the existing expanded configuration of the humic substances (that make binding sites accessible to the metal ions) and the ionization of functional groups, alkaline environment facilitates the association between Fe(III) ions and the lignite-derived humic substances. UV-vis and IR spectra revealed coordination of the metal ions with the carboxylic and phenolic groups of the oxygen-rich humic substances. Fe(III)-humate complexes were proved stable in a wide pH range similar to Fe-EDDHA synthetic chelates. Furthermore, the presence of K⁺ and humic matter increases the agronomic value of this material establishing alternative applications for Megalopolis peaty lignite.     

Programmed Death-Ligand 1 as a Regulator of Tumor Progression and Metastasis

Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint has long been implicated in modeling antitumor immunity; PD-1/PD-L1 axis inhibitors exert their antitumor effects by relieving PD-L1-mediated suppression on tumor-infiltrating T lymphocytes. However, recent studies have unveiled a distinct, tumor-intrinsic, potential role for PD-L1. In this review, we focus on tumor-intrinsic PD-L1 signaling and delve into preclinical evidence linking PD-L1 protein expression with features of epithelial-to-mesenchymal transition program, cancer stemness and known oncogenic pathways. We further summarize data from studies supporting the prognostic significance of PD-L1 in different tumor types. We show that PD-L1 may indeed have oncogenic potential and act as a regulator of tumor progression and metastasis.     

Aryl diazonium functionalization of carbon nanohorns

Carbon nanohorns (CNHs) are a relatively new material within the family of elongated carbon nanostructures. A strategy for their solubilization is presented here. Aryl diazonium functionalization of CNHs has been achieved giving rise to soluble materials in common organic solvents as well as water. The modified CNHs have been characterized by complementary spectroscopic and microscopic means as well as thermal gravimetric analysis and dynamic light scattering measurements.     

Healthcare provider cultural competency: Development and initial validation of a patient report measure.

Objective: Health researchers have proposed that provider cultural competency may contribute to health disparities. Yet, this belief continues to lack empirical support, and this is due in part to measurement issues that have plagued the cultural competency construct. In the present research, we report on the development of a theoretically grounded, generally applicable, and patient report measure of provider cultural competency. Design: Samples of predominantly African American patients (N = 310) were recruited from three urban medical clinics to complete a survey about their relationship with their physician. Main Outcome Measures: We examined the factor structure, validity and other psychometric characteristics of a newly proposed patient report measure of provider cultural competency. Results: Psychometric analyses supported a tripartite model of cultural competency that was comprised of patient judgments of their physician's cultural knowledge, awareness, and skill. In addition, this result was replicated across multiple clinical contexts, while also demonstrating convergent and incremental validity when correlated with measures of trust, satisfaction and discrimination. Conclusion: This newly proposed measure addresses prior limitations in cultural competency measurement and may enhance future research by providing a standardized tool for use in multiple clinical and cultural contexts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unveiling the Essential Role of Arkadia’s Non-RING Elements in the Ubiquitination Process

Arkadia is a positive regulator of the TGFβ-SMAD2/3 pathway, acting through its C-terminal RING-H2 domain and targeting for degradation of its negative regulators. Here we explore the role of regions outside the RING domain (non-RING elements) of Arkadia on the E2-E3 interaction. The contribution of the non-RING elements was addressed using Arkadia RING 68 aa and Arkadia 119 aa polypeptides. The highly conserved NRGA (asparagine-arginine-glycine-alanine) and TIER (threonine-isoleucine-glutamine-arginine) motifs within the 119 aa Arkadia polypeptide, have been shown to be required for pSMAD2/3 substrate recognition and ubiquitination in vivo. However, the role of the NRGA and TIER motifs in the enzymatic activity of Arkadia has not been addressed. Here, nuclear magnetic resonance interaction studies with the E2 enzyme, UBCH5B, C85S UBCH5B-Ub oxyester hydrolysis, and auto-ubiquitination assays were used to address the role of the non-RING elements in E2-E3 interaction and in the enzymatic activity of the RING. The results support that the non-RING elements including the NRGA and TIER motifs are required for E2-E3 recognition and interaction and for efficient auto-ubiquitination. Furthermore, while Arkadia isoform-2 and its close homologue Arkadia 2C are known to interact with free ubiquitin, the results here showed that Arkadia isoform-1 does not interact with free ubiquitin.     

Employee perceptions on the implementation of robotic manufacturing technology.

[Correction Notice: An erratum for this article was reported in Vol 71(3) of Journal of Applied Psychology (see record 2008-10743-001). Several crucial horizontal rules were omitted from Table 2. The corrected table appears in the erratum.] A review of the industrial robotics literature identified 4 areas of employee concern during the implementation of robots: general robotics orientation, job security, management concern, and expected changes. A principal factors analysis of a 58-item questionnaire generated to measure these dimensions extracted 4 factors that reproduced the a priori conceptual areas. Composite scales formed from items loading on these factors yielded acceptable reliabilities. A discriminant analysis using the scale scores indicated significant group differences among 316 manufacturing employees in 3 occupational classes—assembly line workers, job setters, and skilled trades. These results, corroborated by a content analysis of an open-ended question, show that low-skill workers reacted negatively toward the implementation of robots, perceiving them largely as threats to their job security. High-skill workers reacted more positively toward the robots and perceived the implementation as providing opportunities to expand their skills. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rule-based query personalization in digital libraries

Searching a digital library is typically a tedious task. A system can improve information access by building on knowledge about a user acquired in a user profile in order to customize information access both in terms of the information returned in response to a query (query personalization) as well as in terms of the presentation of the results (presentation personalization). In this paper, we focus on query personalization in digital libraries; in particular, we address structured queries involving metadata stored in relational databases. We describe the specification of user preferences at the level of a user profile and the process of query personalization with the use of query-rewriting rules.