A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules.

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states

The complement binding-like domains of the murine homing receptor facilitate lectin activity.

The leukocyte homing receptor (HR), the endothelial leukocyte adhesion molecule, and gmp140/platelet activation-dependent granule membrane protein are members of a family of adhesion molecules, termed the lectin cell adhesion molecules (LEC-CAMS) which are unified by a multi-domain structure containing a lectin motif, an epidermal growth factor-like (egf) motif, and variable numbers of a complement binding-like (CB) motif. Previous data have indicated a predominant role for the lectin motif in cell adhesion directed by the LEC-CAMS, although the egf-like domain of the HR may also play a potential role in cell binding. While the role(s) of the CB domains in the LEC-CAMS is currently not understood, they have been hypothesized to act as rigid spacers or stalks for lectin and perhaps, egf domain presentation. In this paper, we analyze the functional characteristics of murine HR-IgG chimeras containing the lectin, lectin plus egf, and lectin plus egf plus CB domains. The Mel 14 mAb, an adhesion blocking antibody which recognizes a conformational determinant in the N-terminus of the HR lectin domain, shows a significantly decreased affinity for a HR construct which lacks the CB motifs, consistent with the possibility that the CB domains are involved with lectin domain structure. In agreement with this conjecture, HR mutants lacking the CB domains show a profound decrease in lectin-specific interaction with the carbohydrate polyphosphomannan ester, suggesting that the changes in Mel 14 affinity for the lectin domain are reflected in lectin functionality. Various assays investigating the interactions between the HR deletion mutants and the peripheral lymph node high endothelium, including cell blocking, immunohistochemical staining, and radioactively labeled ligand binding, all showed that removal of the CB domains results in a lack of HR adhesive function. These results imply that the CB domains of the HR, and, by analogy, the other members of the LEC-CAM family, may play important structural roles involving induction of lectin domain conformation and resultant functionality

The Logistic Path from the International Space Station to the Moon and Beyond

The period from the loss of the Space Shuttle Columbia in February 2003 to resumption of Space Shuttle flights, planned for May 2005, has presented significant challenges to International Space Station (ISS) maintenance operations. Sharply curtailed upmass capability has forced NASA to revise its support strategy and to undertake maintenance activities that have significantly expanded the envelope of the ISS maintenance concept. This experience has enhanced confidence in the ability to continue to support ISS in the period following the permanent retirement of the Space Shuttle fleet in 2010. Even greater challenges face NASA with the implementation of the Vision for Space Exploration that will introduce extended missions to the Moon beginning in the period of 2015 - 2020 and ultimately see human missions to more distant destinations such as Mars. The experience and capabilities acquired through meeting the maintenance challenges of ISS will serve as the foundation for the maintenance strategy that will be employed in support of these future missions

Differential Subordinations Involving Generalized Bessel Functions

In this paper our aim is to present some subordination and superordination results, by using an operator, which involves the normalized form of the generalized Bessel functions of first kind. These results are obtained by investigating some appropriate classes of admissible functions. We obtain also some sandwich-type results and we point out various known or new special cases of our main results.Comment: 15 pages, accepted in Bulletin of the Malaysian Mathematical Sciences Societ

State of the California current 2012-13: No such thing as an “average” year

This report reviews the state of the California Current System (CCS) between winter 2012 and spring 2013, and includes observations from Washington State to Baja California. During 2012, large-scale climate modes indicated the CCS remained in a cool, productive phase present since 2007. The upwelling season was delayed north of 42°N, but regions to the south, especially 33° to 36°N, experienced average to above average upwelling that persisted throughout the summer. Contrary to the indication of high production suggested by the climate indices, chlorophyll observed from surveys and remote sensing was below average along much of the coast. As well, some members of the forage assemblages along the coast experienced low abundances in 2012 surveys. Specifically, the concentrations of all lifestages observed directly or from egg densities of Pacific sardine, Sardinops sagax, and northern anchovy, Engraulis mordax, were less than previous years’ survey estimates. However, 2013 surveys and observations indicate an increase in abundance of northern anchovy. During winter 2011/2012, the increased presence of northern copepod species off northern California was consistent with stronger southward transport. Krill and small-fraction zooplankton abundances, where examined, were generally above average. North of 42°N, salps returned to typical abundances in 2012 after greater observed concentrations in 2010 and 2011. In contrast, salp abundance off central and southern California increased after a period of southward transport during winter 2011/2012. Reproductive success of piscivorous Brandt’s cormorant, Phalacrocorax penicillatus, was reduced while planktivorous Cassin’s auklet, Ptychoramphus aleuticus was elevated. Differences between the productivity of these two seabirds may be related to the available forage assemblage observed in the surveys. California sea lion pups from San Miguel Island were undernourished resulting in a pup mortality event perhaps in response to changes in forage availability. Limited biological data were available for spring 2013, but strong winter upwelling coastwide indicated an early spring transition, with the strong upwelling persisting into early summer

Leading in White Spaces: The Experience of African American Pastors as Leaders in the Christian Reformed Church in North America (CRCNA)

The Christian Reformed Church in North America (CRCNA) has had mixed results in attracting and maintaining Black leadership. This research seeks to identify the reasons for this mixed record by examining the experiences of nine current and former Black and African American CRCNA leaders. Significant inclusion of Black and African-American leadership in the CRCNA is not only possible, but desired by the individuals interviewed. This work examines various challenges experienced by the pastors that were interviewed, and then provides potential next steps that address these challenges and increase the longevity and success of Black leadership in the CRCNA

State of the California current 2013-14: El niño looming

In 2013, the California current was dominated by strong coastal upwelling and high productivity. Indices of total cumulative upwelling for particular coastal locations reached some of the highest values on record. Chlorophyll a levels were high throughout spring and summer. Catches of upwelling-related fish species were also high. After a moderate drop in upwelling during fall 2013, the California current system underwent a major change in phase. Three major basin-scale indicators, the PDO, the NPGO, and the ENSO-MEI, all changed phase at some point during the winter of 2013/14. The PDO changed to positive values, indicative of warmer waters in the North Pacific; the NPGO to negative values, indicative of lower productivity along the coast; and the MEI to positive values, indicative of an oncoming El Niño. Whereas the majority of the California Current system appears to have transitioned to an El Niño state by August 2014, based on decreases in upwelling and chlorophyll a concentration, and increases in SST, there still remained pockets of moderate upwelling, cold water, and high chlorophyll a biomass at various central coast locations, unlike patterns seen during the more major El Niños (e.g., the 97-98 event). Catches of rockfish, market squid, euphausiids, and juvenile sanddab remained high along the central coast, whereas catches of sardine and anchovy were low throughout the CCS. 2014 appears to be heading towards a moderate El Niño state, with some remaining patchy regions of upwellingdriven productivity along the coast. Superimposed on this pattern, three major regions have experienced possibly non-El Niño-related warming since winter: the Bering Sea, the Gulf of Alaska, and offshore of southern California. It is unclear how this warming may interact with the predicted El Niño, but the result will likely be reduced growth or reproduction for many key fisheries species

The sub-energetic GRB 031203 as a cosmic analogue to GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, associated with the nearby (distance, ~40 Mpc) supernova 1998bw, astronomers have fiercely debated the nature of this event. Relative to bursts located at cosmological distances, (redshift, z~1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed the explosion was sub-energetic by a factor of 10. Here, we report observations of the radio and X-ray afterglow of the recent z=0.105 GRB 031203 and demonstrate that it too is sub-energetic. Our result, when taken together with the low gamma-ray luminosity, suggest that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. Intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRBs 031203 and 980425) may enable us to reveal their expected large population.Comment: To Appear in Nature, August 5, 200

Cost-Effectiveness of Haemorrhoidal Artery Ligation versus Rubber Band Ligation for the Treatment of Grade II–III Haemorrhoids: Analysis Using Evidence from the HubBLe Trial

Aim Haemorrhoids are a common condition, with nearly 30,000 procedures carried out in England in 2014/15, and result in a significant quality-of-life burden to patients and a financial burden to the healthcare system. This study examined the cost effectiveness of haemorrhoidal artery ligation (HAL) compared with rubber band ligation (RBL) in the treatment of grade II–III haemorrhoids. Method This analyses used data from the HubBLe study, a multicentre, open-label, parallel group, randomised controlled trial conducted in 17 acute UK hospitals between September 2012 and August 2015. A full economic evaluation, including long-term cost effectiveness, was conducted from the UK National Health Service (NHS) perspective. Main outcomes included healthcare costs, quality-adjusted life-years (QALYs) and recurrence. Costeffectiveness results were presented in terms of incremental cost per QALY gained and cost per recurrence avoided. Extrapolation analysis for 3 years beyond the trial follow-up, two subgroup analyses (by grade of haemorrhoids and recurrence following RBL at baseline), and various sensitivity analyses were undertaken. Results In the primary base-case within-trial analysis, the incremental total mean cost per patient for HAL compared with RBL was £1027 (95% confidence interval [CI] £782– £1272, p\0.001). The incremental QALYs were 0.01 QALYs (95% CI -0.02 to 0.04, p = 0.49). This generated an incremental cost-effectiveness ratio (ICER) of £104,427 per QALY. In the extrapolation analysis, the estimated probabilistic ICER was £21,798 per QALY. Results from all subgroup and sensitivity analyses did not materially change the base-case result. Conclusions Under all assessed scenarios, the HAL procedure was not cost effective compared with RBL for the treatment of grade II-III haemorrhoids at a cost-effectiveness threshold of £20,000 per QALY; therefore

Concurrent use of prescription drugs and herbal medicinal products in older adults: A systematic review

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The use of herbal medicinal products (HMPs) is common among older adults. However, little is known about concurrent use with prescription drugs as well as the potential interactions associated with such combinations. Objective Identify and evaluate the literature on concurrent prescription and HMPs use among older adults to assess prevalence, patterns, potential interactions and factors associated with this use. Methods Systematic searches in MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, Web of Science and Cochrane from inception to May 2017 for studies reporting concurrent use of prescription medicines with HMPs in adults (≥65 years). Quality was assessed using the Joanna Briggs Institute checklists. The Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre) three stage approach to mixed method research was used to synthesise data. Results Twenty-two studies were included. A definition of HMPs or what was considered HMP was frequently missing. Prevalence of concurrent use by older adults varied widely between 5.3% and 88.3%. Prescription medicines most combined with HMPs were antihypertensive drugs, beta blockers, diuretics, antihyperlipidemic agents, anticoagulants, analgesics, antihistamines, antidiabetics, antidepressants and statins. The HMPs most frequently used were: ginkgo, garlic, ginseng, St John’s wort, Echinacea, saw palmetto, evening primrose oil and ginger. Potential risks of bleeding due to use of ginkgo, garlic or ginseng with aspirin or warfarin was the most reported herb-drug interaction. Some data suggests being female, a lower household income and less than high school education were associated with concurrent use. Conclusion Prevalence of concurrent prescription drugs and HMPs use among older adults is substantial and potential interactions have been reported. Knowledge of the extent and manner in which older adults combine prescription drugs will aid healthcare professionals can appropriately identify and manage patients at risk.Peer reviewedFinal Published versio