Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.     

Path Loss Modelling for Location Service Applications

The aim of this paper is the path loss modelling for the radiolocation services in radio communication networks, particularly in cellular networks. The main results of the measurements obtained in the physical layer of the UMTS are introduced. A new method for the utilization of the multipath propagation phenomenon to improve the estimation of the distance between the MS （mobile station） and the BS （base station） is outlined. This method significantly increases the quality of location services in systems which use a radio interface with DS （direct sequence） CDMA （code division multiple access）.     

Square-wave propagation along coupled coplanar transmission line

Results of modelling square-wave propagation along coupled coplanar transmission line with grounded centre strip conductor are presented. Improved agreement between numerical and experimental data for the near- and far-end crosstalk voltages has confirmed practical significance of inclusion of multimode propagation in non-ideally grounded coplanar lines.     

Induction of release of secretory nonpancreatic phospholipase A2 from human articular chondrocytes

OBJECTIVE: Secretory nonpancreatic phospholipase A2 (sPLA2) is a known inducer/promoter of the inflammatory process in the joints. It correlates with disease activity in adult and juvenile rheumatoid arthritis. Synovial fluids contain high concentrations of sPLA2. We discovered that human articular cartilage contains large quantities of sPLA2 and that culture chondrocytes constitutively synthesize and release sPLA2. To test the mechanism controlling the release of sPLA2, we exposed cultured human articular chondrocytes to cytokines and other agents, known to induce sPLA2 in other cells. METHODS: Chondrocytes obtained from cartilage of normal appearance from rheumatoid and osteoarthritic joints, and from normal, neonatal joints were compared to rabbit articular chondrocytes. Radiolabeled Escherichia coli derived phospholipid assay and ELISA technique using monoclonal antibodies against recombinant human synovial type sPLA2 were employed. The cells were grown as monolayers as well as in alginate beads. RESULTS: Human articular chondrocytes from both arthritic and neonatal joints released sPLA2 constitutively but could not be further stimulated with interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-6, oncostatin M, lipopolysaccharide (LPS), or forskolin. Marked stimulation was observed when the cells were exposed to 8-bromo cyclic adenosine monophosphate (cAMP). Growing the cells as monolayers or in alginate beads did not change the results. In contrast to human cells, rabbit chondrocytes responded to IL-1 beta and IL-1/TNF, but not to TNF-alpha alone, with a very marked increase in extracellular sPLA2 activity. CONCLUSION: Human articular chondrocytes synthesize and constitutively release sPLA2. Such continuous release is most probably responsible for the high concentration of sPLA2 in articular cartilage and may be the source of synovial fluid sPLA2. To our knowledge, human articular chondrocytes are the only sPLA2 producing cells tested to date that do not respond to cytokine stimulation with increased sPLA2 activity; yet enhancement was seen with 8-bromo cAMP. It seems therefore that, human articular chondrocytes possess signalling mechanisms for the release of sPLA2 unlike those from other mammalian cells. The significance of this observation remains to be elucidated.     

Process,Policy, and Implementation of Pool‐Wide Drawdowns on the Upper Mississippi River: A Promising Approach for Ecological Restoration of Large Impounded Rivers

The Upper Mississippi River (UMR) has been developed and subsequently managed for commercial navigation by the U.S. Army Corps of Engineers (USACE). The navigation pools created by a series of lock and dams initially provided a complex of aquatic habitats that supported a variety of fish and wildlife. However, biological productivity declined as the pools aged. The River Resources Forum, an advisory body to the St. Paul District of the USACE, established a multiagency Water Level Management Task Force (WLMTF) to evaluate the potential of water level management to improve ecological function and restore the distribution and abundance of fish and wildlife habitat. The WLMTF identified several water level management options and concluded that summer growing season drawdowns at the pool scale offered the greatest potential to provide habitat benefits over a large area. Here we summarize the process followed to plan and implement pool‐wide drawdowns on the UMR, including involvement of stakeholders in decision making, addressing requirements to modify reservoir operating plans, development and evaluation of drawdown alternatives, pool selection, establishment of a monitoring plan, interagency coordination, and a public information campaign. Three pool‐wide drawdowns were implemented within the St. Paul District and deemed successful in providing ecological benefits without adversely affecting commercial navigation and recreational use of the pools. Insights are provided based on more than 17 years of experience in planning and implementing drawdowns on the UMR. Copyright © 2015 John Wiley & Sons, Ltd.     

Factors regulating cheese shreddability

Two sets of cheeses were evaluated to determine factors that affect shred quality. The first set of cheeses was made up of 3 commercial cheeses, Monterey Jack, Mozzarella, and process. The second set of cheeses was made up of 3 Mozzarella cheeses with varying levels of protein and fat at a constant moisture content. A shred distribution of long shreds, short shreds, and fines was obtained by shredding blocks of cheese in a food processor. A probe tack test was used to directly measure adhesion of the cheese to a stainless-steel surface. Surface energy was determined based on the contact angles of standard liquids, and rheological characterization was done by a creep and recovery test. Creep and recovery data were used to calculate the maximum and initial compliance and retardation time. Shredding defects of fines and adhesion to the blade were observed in commercial cheeses. Mozzarella did not adhere to the blade but did produce the most fines. Both Monterey Jack and process cheeses adhered to the blade and produced fines. Furthermore, adherence to the blade was correlated positively with tack energy and negatively with retardation time. Mozzarella cheese, with the highest fat and lowest protein contents, produced the most fines but showed little adherence to the blade, even though tack energy increased with fat content. Surface energy was not correlated with shredding defects in either group of cheese. Rheological properties and tack energy appeared to be the key factors involved in shredding defects.     

Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations

Supersaturatable cosolvent (S-cosolvent) and supersaturatable self-emulsifying drug delivery systems (S-SEDDS) are designed to incorporate water soluble cellulosic polymers such as hydroxypropyl methylcellulose (HPMC), which may inhibit or retard drug precipitation in vivo. A poorly soluble drug, PNU-91325, was used as a model drug in this study to illustrate this formulation approach. The comparative in vitro studies indicated that the presence of a small amount HPMC in the formulation was critical to achieve a stabilized supersaturated state of PNU-91325 upon mixing with water. An in vivo study was conducted in dogs for assessment of the oral bioavailability of four formulations of PNU-91325. A five-fold higher bioavailability (∼ 60%) was observed from a S-cosolvent formulation containing propylene glycol (PG) + 20 mg/g HPMC as compared to that (∼ 12%) of a neat polyethylene glycol (PEG) 400 formulation. The low bioavailability of the PEG 400 formulation is attributed to the uncontrolled precipitation of PNU-91325 upon dosing, a commonly observed phenomenon with the cosolvent approach. A S-SEDDS formulation composed of 30% w/w Cremophor (surfactant), 9% PEG 400, 5% DMA, 18% Pluronic L44, 20% HPMC, and other minor components showed an oral bioavailability of ∼ 76%, comparable to that of a neat tween formulation (bioavailability: ∼ 68%). The significant improvement of the oral bioavailability of the supersaturatable S-cosolvent and S-SEDDS formulations is attributed to a high free drug concentration in vivo as a result of the generation and stabilization of the supersaturated state due to the incorporation of polymeric precipitation inhibitor.