Design and performance of a fixed, nonaccelerating, guide vane cascade that operates over an inlet flow angle range of 60 deg

A unique set of wind tunnel guide vanes are designed with an inverse design code and analyzed with a panel method and an integral boundary layer code developed at the NASA Lewis Research Center. The fixed guide vanes, 80 feet long with 6-foot chord length, were designed for the NASA Ames 40 x 80/80 x 120 ft Wind Tunnel. Low subsonic flow is accepted over a 60 deg range of inlet angle from either the 40 x 80 leg or the 80 x 120 leg of the wind tunnel, and directed axially into the main leg of the tunnel where drive fans are located. Experimental tests of 1/10-scale models were conducted to verify design calculations

The Stability of Angiotensin I Formed at Room Temperature in the Presence of Ethylenediaminetetraacetate to Subsequent Incubation at 37 °C

Peer Reviewe

The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694.

In ferrets, the selective 5-hydroxytryptamine (5-HT) 5-HT3 receptor antagonist BRL 43694 given as a single injection (0.05-0.5 mg kg-1 i.v.) before cisplatin, or by divided dose (2 x 0.005-2 x 0.5 mg kg-1 i.v.) before and after cisplatin dramatically reduced or abolished the severe cisplatin-induced vomiting. BRL 43694 also substantially reduced the vomiting induced by cyclophosphamide:doxorubicin, and prevented the trimelamol-induced emesis. The severe emesis caused by whole body exposure to X-irradiation was prevented by intravenous or oral BRL 43694. A single i.v. dose of BRL 43694 given during an emetic episode or within the peak emetic period, abolished the vomiting induced by the cytotoxic drugs and by X-irradiation, usually within 30 s. Where the induction of emesis was prevented or subsequently abolished by BRL 43694, the associated behaviour (subjectively assessed as nausea) was also absent or greatly attenuated. BRL 43694 (0.1 mg kg-1 i.v.) did not affect the emesis evoked in dogs by the dopamine agonist apomorphine. The potent anti-emetic activity of BRL 43694 is discussed in terms of potential clinical use, and of the fundamental role that 5-HT3 receptors may play in the mechanisms of nausea and vomiting

Ames 40 X 80/80 X 120 Foot Wind Tunnel: Turning Vanes Design

A number of different turning vanes are designed for the NASA Ames wind tunnel. Computer codes are used to design and analyze the turning vanes to insure that they comply with their individual constraints. The presentation is given in viewgraph format and displays pressure coefficients for the different turning vanes as well as loss coefficients versus inlet flow angles

Effects of neo-adjuvant chemotherapy for oesophago-gastric cancer on neuro-muscular gastric function

Delayed gastric emptying symptoms are often reported after chemotherapy. This study aims to characterise the effects of chemotherapy on gastric neuro-muscular function. Patients undergoing elective surgery for oesophago-gastric cancer were recruited. Acetylcholinesterase, nNOS, ghrelin receptor and motilin expressions were studied in gastric sections from patients receiving no chemotherapy (n = 3) or oesophageal (n = 2) or gastric (n = 2) chemotherapy. A scoring system quantified staining intensity (0–3; no staining to strong). Stomach sections were separately suspended in tissue baths for electrical field stimulation (EFS) and exposure to erythromycin or carbachol; three patients had no chemotherapy; four completed cisplatin-based chemotherapy within 6 weeks prior to surgery. AChE expression was markedly decreased after chemotherapy (scores 2.3 ± 0.7, 0.5 ± 0.2 and 0 ± 0 in non-chemotherapy, oesophageal- and gastric-chemotherapy groups (p < 0.03 each) respectively. Ghrelin receptor and motilin expression tended to increase (ghrelin: 0.7 ± 0.4 vs 2.0 ± 0.4 and 1.2 ± 0.2 respectively; p = 0.04 and p = 0.2; motilin: 0.7 ± 0.5 vs 2.2 ± 0.5 and 2.0 ± 0.7; p = 0.06 and p = 0.16). Maximal contraction to carbachol was 3.7 ± 0.7 g and 1.9 ± 0.8 g (longitudinal muscle) and 3.4 ± 0.4 g and 1.6 ± 0.6 (circular) in non-chemotherapy and chemotherapy tissues respectively (p < 0.05 each). There were loss of AChE and reduction in contractility to carbachol. The tendency for ghrelin receptors to increase suggests an attempt to upregulate compensating systems. Our study offers a mechanism by which chemotherapy markedly alters neuro-muscular gastric function

Optimisation of on-line principal component analysis

Different techniques, used to optimise on-line principal component analysis, are investigated by methods of statistical mechanics. These include local and global optimisation of node-dependent learning-rates which are shown to be very efficient in speeding up the learning process. They are investigated further for gaining insight into the learning rates' time-dependence, which is then employed for devising simple practical methods to improve training performance. Simulations demonstrate the benefit gained from using the new methods.Comment: 10 pages, 5 figure

Support for Integrated Ecosystem Assessments of NOAA’s National Estuarine Research Reserves System (NERRS), Volume I: The Impacts of Coastal Development on the Ecology and Human Well-being of Tidal Creek Ecosystems of the US Southeast

A study was conducted, in association with the Sapelo Island and North Carolina National Estuarine Research Reserves (NERRs), to evaluate the impacts of coastal development on sentinel habitats (e.g., tidal creek ecosystems), including potential impacts to human health and well-being. Uplands associated with southeastern tidal creeks and the salt marshes they drain are popular locations for building homes, resorts, and recreational facilities because of the high quality of life and mild climate associated with these environments. Tidal creeks form part of the estuarine ecosystem characterized by high biological productivity, great ecological value, complex environmental gradients, and numerous interconnected processes. This research combined a watershed-level study integrating ecological, public health and human dimension attributes with watershed-level land use data. The approach used for this research was based upon a comparative watershed and ecosystem approach that sampled tidal creek networks draining developed watersheds (e.g., suburban, urban, and industrial) as well as undeveloped sites. The primary objective of this work was to clearly define the relationships between coastal development with its concomitant land use changes and non-point source pollution loading and the ecological and human health and well-being status of tidal creek ecosystems. Nineteen tidal creek systems, located along the southeastern United States coast from southern North Carolina to southern Georgia, were sampled during summer (June-August), 2005 and 2006. Within each system, creeks were divided into two primary segments based upon tidal zoning: intertidal (i.e., shallow, narrow headwater sections) and subtidal (i.e., deeper and wider sections), and watersheds were delineated for each segment. In total, we report findings on 24 intertidal and 19 subtidal creeks. Indicators sampled throughout each creek included water quality (e.g., dissolved oxygen concentration, salinity, nutrients, chlorophyll-a levels), sediment quality (e.g., characteristics, contaminants levels including emerging contaminants), pathogen and viral indicators, and abundance and genetic responses of biological resources (e.g., macrobenthic and nektonic communities, shellfish tissue contaminants, oyster microarray responses). For many indicators, the intertidally-dominated or headwater portions of tidal creeks were found to respond differently than the subtidally-dominated or larger and deeper portions of tidal creeks. Study results indicate that the integrity and productivity of headwater tidal creeks were impaired by land use changes and associated non-point source pollution, suggesting these habitats are valuable early warning sentinels of ensuing ecological impacts and potential public health threats. For these headwater creeks, this research has assisted the validation of a previously developed conceptual model for the southeastern US region. This conceptual model identified adverse changes that generally occurred in the physical and chemical environment (e.g., water quality indicators such as indicator bacteria for sewage pollution or sediment chemical contamination) when impervious cover levels in the watershed reach 10-20%. Ecological characteristics responded and were generally impaired when impervious cover levels exceed 20-30%. Estimates of impervious cover levels defining where human uses are impaired are currently being determined, but it appears that shellfish bed closures and the flooding vulnerability of headwater regions become a concern when impervious cover values exceed 10-30%. This information can be used to forecast the impacts of changing land use patterns on tidal creek environmental quality as well as associated human health and well-being. In addition, this study applied tools and technologies that are adaptable, transferable, and repeatable among the high quality NERRS sites as comparable reference entities to other nearby developed coastal watersheds. The findings herein will be of value in addressing local, regional and national needs for understanding multiple stressor (anthropogenic and human impacts) effects upon estuarine ecosystems and response trends in ecosystem condition with changing coastal impacts (i.e., development, climate change). (PDF contaions 88 pages

Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes

The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702 together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. We conclude that these properties, whilst imparting beneficial effects on learning and memory, are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data supports the notion that "pure" positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses

Attempting Genetic Inference from Directional Asymmetry during Convergent Hindlimb Reduction in Squamates

Loss and reduction in paired appendages are common in vertebrate evolution. How often does such convergent evolution depend on similar developmental and genetic pathways? For example, many populations of the threespine stickleback and ninespine stickleback (Gasterosteidae) have independently evolved pelvic reduction, usually based on independent mutations that caused reduced Pitx1 expression. Reduced Pitx1 expression has also been implicated in pelvic reduction in manatees. Thus, hindlimb reduction stemming from reduced Pitx1 expression has arisen independently in groups that diverged tens to hundreds of millions of years ago, suggesting a potential for repeated use of Pitx1 across vertebrates. Notably, hindlimb reduction based on the reduction in Pitx1 expression produces left-larger directional asymmetry in the vestiges. We used this phenotypic signature as a genetic proxy, testing for hindlimb directional asymmetry in six genera of squamate reptiles that independently evolved hindlimb reduction and for which genetic and developmental tools are not yet developed: Agamodon anguliceps, Bachia intermedia, Chalcides sepsoides, Indotyphlops braminus, Ophisaurus attenuatuas and O. ventralis, and Teius teyou. Significant asymmetry occurred in one taxon, Chalcides sepsoides, whose left-side pelvis and femur vestiges were 18% and 64% larger than right-side vestiges, respectively, suggesting modification in Pitx1 expression in that species. However, there was either right-larger asymmetry or no directional asymmetry in the other five taxa, suggesting multiple developmental genetic pathways to hindlimb reduction in squamates and the vertebrates more generally

RNA secondary structure formation: a solvable model of heteropolymer folding

The statistical mechanics of heteropolymer structure formation is studied in the context of RNA secondary structures. A designed RNA sequence biased energetically towards a particular native structure (a hairpin) is used to study the transition between the native and molten phase of the RNA as a function of temperature. The transition is driven by a competition between the energy gained from the polymer's overlap with the native structure and the entropic gain of forming random contacts. A simplified Go-like model is proposed and solved exactly. The predicted critical behavior is verified via exact numerical enumeration of a large ensemble of similarly designed sequences.Comment: 4 pages including 2 figure