Folding retractable protective dome for space vehicle equipment

A folding, retractable dome for protecting a feature, such as a docking mechanism, a hatch or other equipment at an exterior surface of a space vehicle, includes a plurality of arcuate ribs, each having opposite ends respectively pinioned at opposite sides of the feature at the surface of the vehicle for rotational movement about an axis of rotation extending through the opposite ends and through an arcuate path of revolution extending over the feature, and a flexible cover attached to each of the ribs such that, in a deployed configuration of the dome, in which adjacent ribs are rotated apart from each other at a maximum relative angle therebetween, the cover is stretched generally tangentially between the adjacent ribs to form a generally arcuate shield over the feature, and in a retracted position of the dome, in which adjacent ribs are rotated together at a minimum relative angle therebetween, the cover is collapsed to define folded pleats between the adjacent ribs

Kappa Opioid receptor-induced aversion requires p38 MAPK activation in VTA dopamine neurons

The endogenous dynorphin-κ opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38α MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(−/−) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38α MAPK activation did not. Surprisingly, while p38α MAPK inactivation blocked U50,488-CPA, p38α MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38α MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that κ opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38α MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of κ receptor activation required arrestin-dependent p38α MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective κ opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

Product Proliferation and the Determination of Slotting and Renewal Allowances

We examine the roles of slotting and renewal allowances in the allocation of scarce retail shelf space. Several contrasting features of the two shelf allocational mechanisms are shown. With slotting allowances, manufacturers can signal the profitability of new products and retailers can screen out the least profitable products. With renewal allowances in a full information context, manufacturers can induce retailers to carry their less profitable products, illustrating a "push" approach to attaining shelf placement: manufacturers of product that enjoy strong consumer "pull* obtain shelf placement without paying renewal allowances. In both cases, product proliferation results in higher slotting and renewal allowances by raising the opportunity cost of shelf space. However, as countervailing leverage against retailers, manufacturers of successful product lines can use their successful products to help attain placement for their relatively weak products

Comparisons Between Spectral Quality Metrics and Analyst Performance in Hyperspectral Target Detection

Quantitative methods to assess or predict the quality of a spectral image continue to be the subject of a number of current research activities. An accepted methodology would be highly desirable for use in data collection tasking or data archive searching in ways analogous to the current prediction of panchromatic image quality through the National Imagery Interpretation Rating Scale (NIIRS) using the General Image Quality Equation (GIQE). A number of approaches to the estimation of quality of a spectral image have been published, but most capture only the performance of automated algorithms applied to the spectral data. One recently introduced metric, however, the General Spectral Utility Metric (GSUM), provides for a framework to combine the performance from the spectral aspects together with the spatial aspects. In particular, this framework allows the metric to capture the utility of a spectral image resulting when the human analyst is included in the process. This is important since nearly all hyperspectral imagery analysis procedures include an analyst. To investigate the relationships between candidate spectral metrics and task performance from volunteer human analysts in conjunction with the automated results, simulated images are generated and processed in a blind test. The performance achieved by the analysts is then compared to predictions made from various spectral quality metrics to determine how well the metrics function. The task selected is one of finding a specific vehicle in a cluttered environment using a detection map produced from the hyperspectral image along with a panchromatic rendition of the image. Various combinations of spatial resolution, number of spectral bands, and signal-to-noise ratios are investigated as part of the effort

Business Models in Emerging Online Services

Due to advances in technology and the rapid growth of online services, a significant number of new and inventive web-based service models and delivery methods have been introduced. Although online resources and services are having an impact on more traditional service delivery mechanisms, it is not yet clear how these emerging mechanisms for online service delivery will result in profitable business models. In this paper, we consider emerging business models for online services and their implications for how services are delivered, used, and paid for. We demonstrate the changing roles of user / consumer and provider / seller. We also discuss the applicability of different business models for various domains

Regulation of the T-type Ca²⁺ channel Cav3.2 by hydrogen sulfide: Emerging controversies concerning the role of H₂S in nociception

Ion channels represent a large and growing family of target proteins regulated by gasotransmitters such as nitric oxide, carbon monoxide and, as described more recently, hydrogen sulfide. Indeed, many of the biological actions of these gases can be accounted for by their ability to modulate ion channel activity. Here, we report recent evidence that H₂S is a modulator of low voltage-activated T-type Ca²⁺ channels, and discriminates between the different subtypes of T-type Ca²⁺ channel in that it selectively modulates Cav3.2, whilst Cav3.1 and Cav3.3 are unaffected. At high concentrations, H₂S augments Cav3.2 currents, an observation which has led to the suggestion that H₂S exerts its pro-nociceptive effects via this channel, since Cav3.2 plays a central role in sensory nerve excitability. However, at more physiological concentrations, H₂S is seen to inhibit Cav3.2. This inhibitory action requires the presence of the redox-sensitive, extracellular region of the channel which is responsible for tonic metal ion binding and which particularly distinguishes this channel isoform from Cav3.1 and 3.3. Further studies indicate that H₂S may act in a novel manner to alter channel activity by potentiating the zinc sensitivity/affinity of this binding site. This review discusses the different reports of H₂S modulation of T-type Ca²⁺ channels, and how such varying effects may impact on nociception given the role of this channel in sensory activity. This subject remains controversial, and future studies are required before the impact of T-type Ca²⁺ channel modulation by H₂S might be exploited as a novel approach to pain management

Prospectus, September 2, 1987

https://spark.parkland.edu/prospectus_1987/1017/thumbnail.jp

Prospectus, August 1988

https://spark.parkland.edu/prospectus_1988/1000/thumbnail.jp

Prospectus, December 15, 1988

https://spark.parkland.edu/prospectus_1988/1032/thumbnail.jp

Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium

Background Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. Procedure This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L -asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. Results Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1 mg/m 2 ). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3 mg/m 2 ). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. Conclusions The combination of bortezomib (1.3 mg/m 2 ) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3 mg/m 2 cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov ( http://clinicaltrials.gov/ct2/show/NCT00440726 ). Pediatr Blood Cancer 2010;55:254–259. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77437/1/22456_ftp.pd