Creating a Student Centered Learning Environment at the University of Denver

A team of faculty members at the University of Denver changed the learning environment in key courses in the Department of Engineering from predominately teacher centered to student centered. Through this funded project new grading methods were implemented, classrooms were renovated and wired with studio layouts to facilitate learning, the Engineering Circuits Laboratory was rewired and instrumented for automated data acquisition and reporting, and two new pedagogical approaches were developed. At the onset of the project, six goals were established related to student learning. The introduction of industry standard hardware and software provided students with unprecedented hands‐on experience and project related activities stimulated faculty innovations in other current and future courses. Assessment results indicate that the new grading system improved the clarity of expectations for students before assignments were given resulting in increased reported motivation for learning in many courses. Even though course GPAs did not always reflect higher achievement on graded work, faculty members firmly believe that deeper understanding was achieved because more complex material was assimilated.     

Immunoregulatory functions of paf-acether. VI. Dual effect on human B cell proliferation

The role of paf-acether (paf), a phospholipid cytokine, in the modulation of human B cell function was investigated. Paf, from 1×10⁻⁵ M to 10⁻⁶ M, decreased B cell proliferation induced by both phorbol myristate acetate (PMA) and anti-IgM antibodies (anti-IgM Ab). By contrast, 1×10⁻⁷ M to 1×10⁻⁹ M paf enhanced PMA triggered, but not anti-IgM triggered B cell proliferation. B cell proliferation was modulated between 24 and 72 hr of culture indicating that the effect of paf did not merely reflect a shift in proliferation kinetics. Interestingly, paf also enhanced the spontaneous proliferation of a Burkitt lymphoma-derived B cell line, Raji, which suggests that paf can directly act on B cells. The modulatory effect of paf on peripheral blood B cells was independent of PMA concentration, yet the effect on Raji cells was dependent upon cell density. The data suggest that paf is a potent modulator of B cell function, and may be involved in the control of humoral immune response. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 1989.     

Pilot proteomic analysis of cerebrospinal fluid in Alzheimer's disease

Proteomic analysis of cerebrospinal fluid (CSF) holds great promise in understanding the progression of neurodegenerative diseases, including Alzheimer's disease (AD). As one of the primary reservoirs of neuronal biomolecules, CSF provides a window into the biochemical and cellular aspects of the neurological environment. CSF can be drawn from living participants allowing the potential alignment of clinical changes with these biochemical markers. Using cutting-edge mass spectrometry technologies, we perform a streamlined proteomic analysis of CSF. We quantify greater than 700 proteins across 10 pairs of age- and sex-matched participants in approximately one hour of analysis time each. Using the paired participant study structure, we identify a small group of biologically relevant proteins that show substantial changes in abundance between cognitive normal and AD participants, which were then analyzed at the peptide level using parallel reaction monitoring experiments. Our findings suggest the utility of fractionating a single sample and using matching to increase proteomic depth in cerebrospinal fluid, as well as the potential power of an expanded study.     

Quantitative and reliable in vitro method combining scanning electron microscopy and image analysis for the screening of osteotropic modulators

The increased generation and up-regulated activity of bone resorbing cells (osteoclasts) play a part in the impairment of bone remodeling in many bone diseases. Numerous drugs (bisphosphonates, calcitonin, selective estrogen receptor modulators) have been proposed to inhibit this increased osteoclastic activity. In this report, we describe a pit resorption assay quantified by scanning electron microscopy coupled with image analysis. Total rabbit bone cells with large numbers of osteoclasts were cultured on dentin slices. The whole surface of the dentin slice was scanned and both the number of resorption pits and the total resorbed surface area were measured. Resorption pits appeared at 48 h and increased gradually up to 96 h. Despite the observation of a strong correlation between the total resorption area and the number of pits, we suggest that area measurement is the most relevant marker for osteoclastic activity. Osteotropic factors stimulating or inhibiting osteoclastic activity were used to test the variations in resorption activity as measured with our method. This reproducible and sensitive quantitative method is a valuable tool for screening for osteoclastic inhibitors and, more generally, for investigating bone modulators.     

Microbiota-Derived Extracellular Vesicles Detected in Human Blood from Healthy Donors

The microbiota constitutes an important part of the holobiont in which extracellular vesicles (EVs) are key players in health, especially regarding inter- and intra-kingdom communications. Analysis of EVs from the red blood cell concentrates of healthy donors revealed variable amounts of OmpA and LPS in 12 of the 14 analyzed samples, providing indirect experimental evidence of the presence of microbiota EVs in human circulating blood in the absence of barrier disruption. To investigate the role of these microbiota EVs, we tracked the fusion of fluorescent Escherichia coli EVs with blood mononuclear cells and showed that, in the circulating blood, these EVs interacted almost exclusively with monocytes. This study demonstrates that bacterial EVs constitute critical elements of the host–microbiota cellular communication. The analysis of bacterial EVs should thus be systematically included in any characterization of human EVs.     

Antivirulence Isoquinolone Mannosides: Optimization of the Biaryl Aglycone for FimH Lectin Binding Affinity and Efficacy in the Treatment of Chronic UTI

Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize the bladder epithelium during urinary tract infection (UTI). Previously reported FimH antagonists exhibit good potency and efficacy, but low bioavailability and a short half‐life in vivo. In a rational design strategy, we obtained an X‐ray structure of lead mannosides and then designed mannosides with improved drug‐like properties. We show that cyclizing the carboxamide onto the biphenyl B‐ring aglycone of biphenyl mannosides into a fused heterocyclic ring, generates new biaryl mannosides such as isoquinolone 22 (2‐methyl‐4‐(1‐oxo‐1,2‐dihydroisoquinolin‐7‐yl)phenyl α‐d ‐mannopyranoside) with enhanced potency and in vivo efficacy resulting from increased oral bioavailability. N‐Substitution of the isoquinolone aglycone with various functionalities produced a new potent subseries of FimH antagonists. All analogues of the subseries have higher FimH binding affinity than unsubstituted lead 22 , as determined by thermal shift differential scanning fluorimetry assay. Mannosides with pyridyl substitution on the isoquinolone group inhibit bacteria‐mediated hemagglutination and prevent biofilm formation by UPEC with single‐digit nanomolar potency, which is unprecedented for any FimH antagonists or any other antivirulence compounds reported to date.     

High‐Pressure High‐Temperature Transparent Fixed‐Bed Reactor for Operando Gas‐Liquid Reaction Follow‐up

A 3‐MPa, 350 °C fixed‐bed reactor was designed to follow‐up gas‐liquid‐solid reactions on a millimetric size heterogeneous catalyst with Raman spectroscopy. The transparent reactor is a quartz cylinder enclosed in a Joule effect heated stainless‐steel tube. A methodology to determine how to focus the microscope for liquid and solid phase characterization is presented. The setup was validated by performing diesel hydrodesulfurization on a CoMo/alumina extrudate catalyst with a conversion very close to expected values along with the acquisition of Raman spectra of the solid catalyst showing an evolution of the catalyst phase during sulfidation.