Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

Scalable semantic brokering over dynamic heterogeneous data sources in InfoSleuth/spl trade/

InfoSleuth is an agent-based system for information discovery and retrieval in a dynamic, open environment. Brokering in InfoSleuth is a matchmaking process, recommending agents that provide services to agents requesting services. This paper discusses InfoSleuth's distributed multibroker design and implementation. InfoSleuth's brokering function combines reasoning over both the syntax and semantics of agents in the domain. This means the broker must reason over explicitly advertised information about agent capabilities to determine which agent can best provide the requested services. Robustness and scalability issues dictate that brokering must be distributable across collaborating agents. Our multibroker design is a peer-to-peer system that requires brokers to advertise to and receive advertisements from other brokers. Brokers collaborate during matchmaking to give a collective response to requests initiated by nonbroker agents. This results in a robust, scalable brokering system.     

Utilizing endoscopic technology to reveal real-time proteomic alterations in response to chemoprevention

Cancer chemoprevention approaches use either pharmacological or dietary agents to impede, arrest or reverse the carcinogenic process. Although several agents have shown effectiveness against colon cancer, present intervention strategies provide only partial reduction. In this study, we utilized high-resolution endoscopy to obtain colon tumor biopsy specimens from Apc mutant mice before and after 2-wk sulindac intervention. To acquire information beyond genomics, proteome analysis using the ProteomeLab PF2D platform was implemented to generate 2-D protein expression maps from biopsies. Chromatograms produced common signature profiles between sulindac and nonsulindac treated samples, and contrasting profiles termed "fingerprints". We selected a double peak that appeared in tumor biopsies from sulindac-treated mice. Further analyses using MS sequencing identified this protein as histone H2B. The location of H2B in the 1(st) dimension strongly suggested PTM, consistent with identification of two oxidized methionines. While further studies on sulindac proteomic fingerprints are underway, this study demonstrates the feasibility and advantages of "real-time" proteomic analysis for obtaining information on biomarker discovery and drug activity that would not be revealed by a genetic assay. This approach should be broadly applicable for assessing lesion responsiveness in a wide range of translational and human clinical studies.     

Equations to predict female manual arm strength based on hand location relative to the shoulder

The purpose of this study was to develop regression equations to predict manual arm strength for a wide variety of hand locations within the reach envelope. Maximum voluntary manual arm strength was determined from 71 female participants in six exertion directions (superior, inferior, anterior, posterior, medial and lateral), in a total of 28 hand locations. Forces ranged from 51.3 to 164.4 N, and had a pooled coefficient of variation of 29.9%. Across all 168 combinations of hand locations and exertion directions, the multivariate regression equations explained 92.5% of the variance and had a root mean square error (RMSE) of only 6.4 N, using only the anterior, lateral and vertical location of the hand relative to the active shoulder joint as inputs. These equations provide a proof-of-principle for our novel regression approach, and represent a first step towards a more comprehensive equation to estimate maximum acceptable forces for occupational tasks.     

An indirect testing approach for characterizing pressure profiles of compression bandages and hosiery

As outlined in compression therapy literature, the performance of a compression textile can be characterized by its stiffness and interface pressure. In this study, an indirect approach for measuring pressure from a set of compression bandages and hosiery was developed, from which rigidity (EI) values were determined, and tension–elongation curves and pressure-elongation data were calculated. The calculated pressure values were compared against PicoPress sensor readings measured on 10 participants. Results showed that the correlation between both approaches varied among bandage and hosiery samples.     

Effects of antimicrobial use in agricultural animals on drug-resistant foodborne salmonellosis in humans: A systematic literature review

Controversy continues concerning antimicrobial use in food animals and its relationship to drug-resistant infections in humans. We systematically reviewed published literature for evidence of a relationship between antimicrobial use in agricultural animals and drug-resistant meat or dairy-borne non-typhoidal salmonellosis in humans. Based on publications from the United States (U.S.), Canada, and Denmark from January 2010 to July 2014, 858 articles received title and abstract review, 104 met study criteria for full article review with 68 retained for which data are presented. Antibiotic exposure in both cattle and humans found an increased likelihood of Salmonella colonization, whereas in chickens, animals not exposed to antibiotics (organic) were more likely to be Salmonella positive and those that had antibiotic exposure were more likely to harbor antimicrobial resistant Salmonella organisms. In swine literature, only tylosin exposure was examined and no correlation was found among exposure, Salmonella colonization, or antimicrobial resistance. No studies that identified farm antimicrobial use also traced antimicrobial-resistant Salmonella from farm to fork.     

Searching for differences in race: Is there evidence for preferential detection of other-race faces?

Previous research has suggested that like animal and social fear-relevant stimuli, other-race faces (African American) are detected preferentially in visual search. Three experiments using Chinese or Indonesian faces as other-race faces yielded the opposite pattern of results: faster detection of same-race faces among other-race faces. This apparently inconsistent pattern of results was resolved by showing that Asian and African American faces are detected preferentially in tasks that have small stimulus sets and employ fixed target searches. Asian and African American other-race faces are found slower among Caucasian face backgrounds if larger stimulus sets are used in tasks with a variable mapping of stimulus to background or target. Thus, preferential detection of other-race faces was not found under task conditions in which preferential detection of animal and social fear-relevant stimuli is evident. Although consistent with the view that same-race faces are processed in more detail than other-race faces, the current findings suggest that other-race faces do not draw attention preferentially. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On thermal and vibrational properties of LaGaO3 single crystals

The thermal expansion and vibrational properties of [1 0 0] and [0 0 1] LaGaO₃ single crystals have been studied by thermal mechanical analysis and micro-Raman spectroscopy. A first-order orthorhombic to rhombohedral phase transition has been confirmed by both techniques, as well as by in situ heating using optical microscopy. The appearance of a metastable intermediate phase, tentatively assigned as monoclinic, has been detected both by optical microscopy and Raman spectroscopy upon heating of the [1 0 0] and [0 0 1] LaGaO₃ single crystals. Not only temperature, but the stress-induced orthorhombic to rhombohedral phase transition has also been detected by Raman mapping of the residual impression made by Vickers indentation. The position map of bands belonging to the lower-temperature/pressure orthorhombic and the higher-temperature/pressure rhombohedral phase show that the rhombohedral phase is located inside the impression, where the applied indentation stresses are the highest, whereas no rhombohedral phase is detected outside the impression, where the surface has not been altered by contact stresses.     

Differentiating stages of smoking intensity among adolescents: Stage-specific psychological and social influences.

Researchers' understanding of the impact of sociocultural and psychological factors on the various stages of adolescent smoking update is limited. Using national data, the authors examined transitions across smoking stages among adolescents (N=20,747) as a function of interpersonal, familial, and peer domains. Peer smoking was particularly influential on differentiating regular smoking, whereas alcohol use was most influential on earlier smoking. Although significant, depression and delinquency were attenuated in the context of other variables. Higher school grade was more likely to differentiate regular smoking from earlier smoking stages, whereas African American ethnicity and connectedness to school and family were protective of smoking initiation. Results lend support for an interactional approach to adolescent smoking, with implications for stage-matched prevention and intervention applications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

What Makes a Good City in Pre-schoolers' Eyes? Findings from Participatory Planning Projects in Australia and New Zealand

Pre-schooler's voices are absent in urban planning and design. With the possible exception of playgrounds, there is limited knowledge about their experiences in and expectations for urban environments. This paper discusses pre-schoolers' aspirations and desires for aesthetic and accessible green spaces as well as social and physical connectedness. Although this age range has so far been limited in its ability to inform policy and decision-makers, it is argued that pre-schoolers have the capacity and capability of making valuable contributions to design. In the eyes of pre-schoolers, creating a good city means to live in a safe place full of diverse destinations in which they can become streetwise and socialize as part of society.