Picoliter-volume inkjet printing into planar microdevice reservoirs for low-waste, high-capacity drug loading.

Oral delivery of therapeutics is the preferred route for systemic drug administration due to ease of access and improved patient compliance. However, many therapeutics suffer from low oral bioavailability due to low pH and enzymatic conditions, poor cellular permeability, and low residence time. Microfabrication techniques have been used to create planar, asymmetric microdevices for oral drug delivery to address these limitations. The geometry of these microdevices facilitates prolonged drug exposure with unidirectional release of drug toward gastrointestinal epithelium. While these devices have significantly enhanced drug permeability in vitro and in vivo, loading drug into the micron-scale reservoirs of the devices in a low-waste, high-capacity manner remains challenging. Here, we use picoliter-volume inkjet printing to load topotecan and insulin into planar microdevices efficiently. Following a simple surface functionalization step, drug solution can be spotted into the microdevice reservoir. We show that relatively high capacities of both topotecan and insulin can be loaded into microdevices in a rapid, automated process with little to no drug waste

GaN epitaxy on thermally treated c-plane bulk ZnO substrates with O and Zn faces

ZnO is considered as a promising substrate for GaNepitaxy because of stacking match and close lattice match to GaN. Traditionally, however, it suffered from poor surface preparation which hampered epitaxialgrowth in general and GaN in particular. In this work, ZnO substrates with atomically flat and terrace-like features were attained by annealing at high temperature in air. GaNepitaxial layers on such thermally treated basal plane ZnO with Zn and O polarity have been grown by molecular beam epitaxy, and two-dimensional growth mode was achieved as indicated by reflection high-energy electron diffraction. We observed well-resolved ZnO and GaN peaks in the high-resolution x-ray diffraction scans, with no Ga2ZnO4 phase detectable. Low-temperature photoluminescence results indicate that high-quality GaN can be achieved on both O- and Zn-face ZnO

Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis

It is widely believed that the molecular and cellular features of a tumor reflect its cell of origin and can thus provide clues about treatment targets. The retinoblastoma cell of origin has been debated for over a century. Here, we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell type-specific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Furthermore, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro

Interspecific Variation in Life History Relates to Antipredator Decisions by Marine Mesopredators on Temperate Reefs

As upper-level predatory fishes become overfished, mesopredators rise to become the new ‘top’ predators of over-exploited marine communities. To gain insight into ensuing mechanisms that might alter indirect species interactions, we examined how behavioural responses to an upper-level predatory fish might differ between mesopredator species with different life histories. In rocky reefs of the northeast Pacific Ocean, adult lingcod (Ophiodon elongatus) are upper-level predators that use a sit-and-wait hunting mode. Reef mesopredators that are prey to adult lingcod include kelp greenling (Hexagrammos decagrammus), younger lingcod, copper rockfish (Sebastes caurinus) and quillback rockfish (S. maliger). Across these mesopredators species, longevity and age at maturity increases and, consequently, the annual proportion of lifetime reproductive output decreases in the order just listed. Therefore, we hypothesized that the level of risk taken to acquire resources would vary interspecifically in that same order. During field experiments we manipulated predation risk with a model adult lingcod and used fixed video cameras to quantify interactions between mesopredators and tethered prey (Pandalus shrimps). We predicted that the probabilities of inspecting and attacking tethered prey would rank from highest to lowest and the timing of these behaviours would rank from earliest to latest as follows: kelp greenling, lingcod, copper rockfish, and quillback rockfish. We also predicted that responses to the model lingcod, such as avoidance of interactions with tethered prey, would rank from weakest to strongest in the same order. Results were consistent with our predictions suggesting that, despite occupying similar trophic levels, longer-lived mesopredators with late maturity have stronger antipredator responses and therefore experience lower foraging rates in the presence of predators than mesopredators with faster life histories. The corollary is that the fishery removal of top predators, which relaxes predation risk, could potentially lead to stronger increases in foraging rates for mesopredators with slower life histories

A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology

Native Village of Kwinhagak Trip Report: Assessment of Mold and Moisture Conditions

Jeff Gordon from the Building Research Council (BRC) at the University of Illinois Urbana-Champaign, and Robert Nemeth of Magna Systems, Inc. conducted a site visit to the Native Village ofKwinhagak on March 30,2004. David Vought of the HUD Alaska Office of Native American Programs, Ford Kuramoto from Magna Systems, and John Davies from the Cold Climate Housing Research Center, also participated in the site visit. The purpose of the site visit was to provide technical assistance to the Native Village of K winhagak in assessing mold and moisture conditions in housing units and to meet with various other groups to discuss mold and moisture issues. This summarizes the site visit. A detailed analysis of the findings and recommendations is found in the attached report, entitled: Native Village of Kwinhagak Technical Housing Assessment Report: Examining Mold and Moisture Conditions in Kwinhagak Housing.U.S. Department of Housing and Urban Development, Office of Native American Program

Bad River Trip Report: Assessment of Mold and Moisture Conditions

Jeff Gordon and Bill Rose from the Building Research Council (BRC) at the University of lllinois Urbana-Champaign and Robert Nemeth of Magna Systems conducted a site visit at Bad River Reservation on December 3-4, 2002. The purpose of the site visit was to provide technical assistance to the Bad River Housing Authority in assessing mold and moisture condition in housing units. This is a summary report of activities and issues addressed while on site. A detailed analysis of the findings and recommendations is found in the attached reports.U.S. Department of Housing and Urban Development, Office of Native American Program

Cherokee Nation Trip Report: Assessment of Mold and Moisture Conditions

Jeff Gordon from the Building Research Council (BRC) at the University of lllinois Urbana-Champaign, and Robert Nemeth of Magna Systems, conducted a site visit at the Cherokee Nation on January 14-16,2003. The purpose of the site visit was to provide technical assistance to the Cherokee Nation Housing Authority in assessing mold and moisture conditions in housing units. This is a summary report of activities and issues addressed while on site. A detailed analysis of the findings and recommendations is found in the attached reports.U.S. Department of Housing and Urban Development, Office of Native American Program