5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Relationships between urbanization and the oak resource of the Minneapolis/St. Paul Metropolitan area from 1991 to 1998

Urbanization was associated with loss and transformation of the oak forest in the Twin Cities (Minneapolis and St. Paul) metropolitan area (TCMA) over a recent 7-year interval. Between 1991 and 1998, urbanization increased based on several indicators: population density, area of developed land, and area of impervious surface—total impervious area and area within three classes of increasing degree of imperviousness (protected, affected, and degraded). We quantified relationships between changes in urbanization and changes in several parameters describing the oak forest at the scale of ecological subsection. Increased total and affected impervious area were strongly correlated with decreased area of oak forest when changes of the urbanization indicators and oak were expressed as percentages of the subsection area. Relationships were reversed when changes were expressed as percentages of the 1991 values. Increased population density was strongly correlated with increased loss in numbers and increased isolation of oak patches, but weakly correlated with loss of oak forest area. This is the first study to quantify relationships between changes in urbanization and changes in a specific forest cover type. Our results demonstrate complexities of urbanization impacts on a metropolitan forest resource, and highlight the importance of selected variables, spatial and temporal scales, and expressions of change when quantifying these relationships.     

Factive Presuppositions, Accommodation and Information Structure

There are three ways to refer to a fact from the complement of afactive verb: (1) Via abstract object anaphoric reference, or, witha full sentential complement that will be interpreted either (2) asa bound presupposition or (3) as triggering a presupposition of afact that will have to be accommodated. Spoken corpus examplesreveal that these three possibilities differ in relation to thetype of information they tend to contribute, and this has twoeffects. First, the information status of the fact and its role inthe discourse seem to affect the preference for one constructionover another in a particular context. Second, presupposed factivecomplements that need to be accommodated tend to be hearer-new andthe focus of the utterance, meaning that information structureseems to contribute to the felicity of accommodation ofpresupposed facts.     

SlideBar: Analysis of a linear input device

The SlideBar is a physical linear input device for absolute position control of 1° of freedom, consisting of a physical slider with a graspable knob positioned near or attached to the keyboard. Its range of motion is directly mapped to a one dimensional input widget such as a scrollbar. The SlideBar provides absolute position control in one dimension, is usable in the non-dominant hand in conjunction with a pointing device, and offers constrained passive haptic feedback. These characteristics make the device appropriate for the common class of tasks characterized by one-dimensional input and constrained range of operation. An empirical study of three devices (SlideBar, mouse controlled scrollbar, and mousewheel) shows that for common scrolling tasks, the SlideBar has a significant advantage over a standard mouse controlled scrollbar in user preference. In addition, users tended to prefer it over the mousewheel (without statistical significance).     

Social environmental selection as a mediator of gender, ethnic, and personality effects on college student drinking.

Structural equation modeling was used to test the mediational role of social environmental selection on alcohol use in cross-sectional samples of 447 students from a rural state university and 421 students from an urban private university. Results showed that male gender, White ethnicity, and sensation seeking were uniquely associated with greater alcohol use. Mediational analyses indicated that socioenvironmental factors (i.e., Greek involvement, friends' approval of drinking/getting drunk) were positively associated with alcohol use and significantly accounted for parts of the effects of ethnicity and sensation seeking, but not gender, on alcohol use. Results suggest that White students and those high on sensation seeking may drink more heavily in college, in part because they select social environments in which alcohol use is encouraged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contracting, prompting, and reinforcing substance use disorder continuing care: A randomized clinical trial.

Although continuing care is strongly related to positive treatment outcomes for substance use disorder (SUD), participation rates are low and few effective interventions are available. In a randomized clinical trial with 150 participants (97% men), 75 graduates of a residential Veterans Affairs Medical Center SUD program who received an aftercare contract, attendance prompts, and reinforcers (CPR) were compared to 75 graduates who received standard treatment (STX). Among CPR participants, 55% completed at least 3 months of aftercare, compared to 36% in STX. Similarly, CPR participants remained in treatment longer than those in STX (5.5 vs. 4.4 months). Additionally, CPR participants were more likely to be abstinent compared to STX (57% vs. 37%) after 1 year. The CPR intervention offers a practical means to improve adherence among individuals in SUD treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The incompatibility of knowledge regimes: consequences of the material world for cross-domain work

In this paper, we argue that successful integration of knowledge across work domains in the short-term can mask the generation of long-term consequences. We explore a setting, the introduction of environmental considerations into semiconductor manufacturing, where the eventual adoption of common measurement artifacts and associated practices enabled knowledge integration, but failed to address significant underlying consequences. Drawing from observational, interview, and archival data we develop an understanding of the work practices of the Tech and EnviroTech groups as structured by the material world and broader collective conventions. We introduce the concept of knowledge regime to outline the differences in knowledge across these work domains. More specifically, we find that differences in the causal specificity and developmental time horizon of knowledge and the measurement artifacts that result contribute to the relative power of one knowledge regime over another. Understanding these sources of incompatibility provides insight into the design requirements of information systems as boundary objects for knowledge integration, but also specifies the potential limits to any design effort.