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.     

Intrinsic Volume Changes of Self-propagating Synthesis

The final product(s) of self-propagating synthesis are shown to be intrinsically denser than the starting reactants. This behavior results in intrinsic decreases in the sample volume that increase with both the heat of reaction and the adiabatic combustion temperature. Forming of liquid product(s) during reaction simply adds another intrinsic source of porosity, i.e. changes in volume on product solidification. Thus, obtaining fully dense bodies from self-propagating synthesis requires a mechanism for reducing porosity, e.g. hot-pressing.     

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.     

Insect sex pheromones

The half-lives (t _1/2) for evaporative loss ofn-alkyl andn-alkenyl acetates from rubber septa were determined at temperatures varying from 15 to 35 °C. The changes int _1/2 with temperature gave high correlations with the equation, Int _1/2 = H/RT+y _o where H is the heat of vaporization,R is the gas constant,T is the absolute temperature, andy _o is a constant. Half-lives changed dramatically with temperature and the degree of change with temperature increased with increasing molecular weight. For mixtures, component ratios changed with temperature, but the degree was modest. At 20 °C there was a 7.5-fold ratio oft _1/2 between members of the homologousn-alkyl orn-alkenyl acetates differing by two carbon atoms. The large change int _1/2 with temperature and with number of carbon atoms is a consequence of the thermodynamic relationships and the temperature range of pheromone usage. Therefore, a similar degree of change inf _1/2 with temperature and number of carbon atoms will apply to other formulations of the same type (those in which the rate of evaporation is first order). The values oft _1/2 at 20 °C mainly agreed very well with those reported previously at room temperature. However, our previously reported values for pentadecyl and hexadecyl acetate were revised. Half-lives were shown to depend on the vapor pressure of a compound in the formulation substrate, but not on the vapor pressure of the pure compound.Mention of a commercial or proprietary product does not constitute an endorsement by the USDA.     

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.     

Technical note: Use of an automated grooming brush by heifers and potential for radiofrequency identification-based measurements of this behavior

Healthy cattle readily use grooming brushes but this behavior subsides when animals become ill. Tracking use of a brush may provide an opportunity for health monitoring, especially if the process could be automated. We assessed how healthy heifers groom themselves on a brush and hypothesized that radiofrequency identification (RFID) could be used to accurately and automatically record this behavior. Angus and Hereford heifers (n = 16) were fitted with 2 ultra-high-frequency RFID ear tags and monitored in groups of 8 while housed in a pen with an electronic brush, video cameras, and 4 RFID antennas. Each heifer was observed for a 6-h period using continuous video recordings, and brush contact was characterized in terms of anatomic region involved (head/neck, trunk, or posterior) and when not touching the brush but within 1 body length of it. The RFID data were collected for the same period and then processed such that intervals of up to 16 s with no detections but contained between 2 recordings were also considered positive (animal in brush proximity). Brush proximity (RFID) was regressed against brush contact duration (video) and the sensitivity and specificity for each individual heifer calculated. Across heifers, the majority of brush use involved the head/neck, although a few heifers demonstrated relatively large amounts of posterior contact, which contributed to false-negative readings when antennas failed to read the ear tags. Furthermore, for the majority of time that animals were near the brush, they were not in contact with it but rather standing or lying nearby, resulting in false-positive readings. It follows that the ability of the RFID system to accurately detect brush contact varied widely across individual heifers (sensitivity 0.54–1.0; specificity 0.59–0.98), with RFID generally overestimating the duration of brush proximity relative to actual time spent in brush contact. The implication is that RFID-based ear tag recording of brush proximity relative to continuous video observations of contact does not yield accurate results in certain heifers and therefore, as currently configured, is not a reliable representation of this type of grooming behavior.     

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)