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ABSTRACTAquatic and leisure centres (ALCs) are important community spaces that contribute to the health and well-being of users, and to the economy, yet the actual value of the facilities and services provided is difficult to measure. In order to quantify the value of ALCs, the authors developed a well-being (reduced risk of chronic disease, mental illness and drowning, and improved productivity), social (educational uplift and volunteer hours supported) and economic (Gross Value Add and employment) value model. Using a sample of Western Australian ALCs, the well-being and social value component of the model indicates that, on average, an ALC provides $1.79m in overall well-being and social value; while from an economic perspective, generates $1.03m in direct GVA and 34 direct jobs. As key players in planning for healthier and happier communities, the current model empowers ALC practitioners to articulate the holistic value of an individual ALC.

Cold central plant recycling (CCPR) of asphalt mixtures continues to grow in interest among agencies and asphalt mixture suppliers. However, one implementation challenge has been the need to invest in new equipment to produce the mixture. In 2015, the National Center for Asphalt Technology (NCAT) worked with a local contractor to produce a CCPR mixture through a standard hot-mix asphalt (HMA) plant. The mix was then placed in a test section on the NCAT Pavement Test Track with a highly modified dense graded HMA overlay. The process used to produce the mixture in the HMA plant is outlined along with the performance of the mixture after heavy truck loading in comparison with a control section with a highly modified dense graded hot-mix asphalt in lieu of CCPR. After 17 million equivalent single axle loads the test section containing the CCPR mixture is performing as well as the control section. This shows that CCPR can be successfully produced using an HMA plant, which may encourage mix suppliers and agencies to conduct trial projects with CCPR, implement CCPR into standard practice, and further justify new CCPR equipment investments.

ABSTRACTErgot alkaloids, a class of mycotoxins associated with ergotism, act as agonists on serotonin (5HT) receptors, specifically 5HT2a, which mediate smooth muscle contraction and vasoconstriction. The objective of this study was to examine the impact of ergot alkaloid exposure during mid and late gestation on microscopic placental structure and vascular development. Ewes were fed endophyte-infected tall fescue seed containing ergot alkaloids (E+/E+, 1.77 mg ewe−1d−1) or endophyte-free tall fescue seed (E-/E-, 0 mg ergot alkaloids) during both mid (d 35 to d 85) and late gestation (d 86 to d 133). On d 133 of gestation, a terminal surgery was performed and two placentomes of the type B morphology were collected for microscopic analyses. Amorphous connective tissue regions were larger (p< 0.0001) and more numerous (p= 0.025) in the placentome of ergot alkaloid exposed ewes. Staining showed no difference (p= 0.83) in the number of vessels present, but luminal area of maternal vasculature was 117% greater (p< 0.0001) in ergot alkaloid exposed ewes. Results showed that exposure to ergot alkaloids during gestation slowed maturation of the fetal villi as indicated by greater amorphous connective tissue regions, and altered size and shape of blood vessels to counteract reductions in blood flow caused by vasoconstriction.

Fourth day of Christmas On December 28, 1972, the RVAH-13 tactical crew of Lt. Cdr. Al Agnew, pilot, and Lt. Mike Haifley, RAN, had flown on the Enterprise's first launch of the day and hours later went on a second mission. Lt. Cdr. Art Skelly and his RAN, Lt. JG Joe Shevlin, survived one of the strangest events of the Vigilante's career. FEATURES The Vigilante was doing 650 knots near the North Vietnamese port of Hon Gai when there was a huge explosion behind the tail from either heavy caliber antiaircraft fire or an SA-2 missile. On fire and with the flight controls failed, the crew, Lt. Cdr. James Bell, pilot, and Lt. Cdr. "Duffy" Hutton, RAN, ejected and landed in the small islands off the coast. [Extracted from the article]

Deep sea geological records indicate that Antarctic ice-sheet growth and decay is strongly influenced by the Earth’s astronomical variations (known as Milankovitch cycles), and that the frequency of the glacial–interglacial cycles changes through time. Here we examine the emergence of a strong obliquity (axial tilt) control on Antarctic ice-sheet evolution during the Miocene by correlating the Antarctic margin geological records from 34 to 5 million years ago with a measure of obliquity sensitivity that compares the variance in deep sea sediment core oxygen-isotope data at obliquity timescales with variance of the calculated obliquity forcing. Our analysis reveals distinct phases of ice-sheet evolution and suggests the sensitivity to obliquity forcing increases when ice-sheet margins extend into marine environments. We propose that this occurs because obliquity-driven changes in the meridional temperature gradient affect the position and strength of the circum-Antarctic easterly flow and enhance (or reduce) ocean heat transport across the Antarctic continental margin. The influence of obliquity-driven changes in ocean dynamics is amplified when marine ice sheets are extensive, and sea ice is limited. Our reconstruction of the Antarctic ice-sheet history suggests that if sea-ice cover decreases in the coming decades, ocean-driven melting at the ice-sheet margin will be amplified.

ABSTRACTGenerally, it is assumed that the well-being of rural communities is linked to their level of resilience. However, despite the importance of community resilience, and its potential to underpin long-term economic development, assessing community perspectives regarding local conditions necessary to support resilience are often ignored during the planning phases of tourism development projects in many areas of the world, especially in countries such as Vietnam, which generally employ top-down planning processes. The purpose of this study is to address this oversight by using household survey techniques to investigate residents’ attitudes toward three components of community resilience, environmental, social, and economic resilience, in the context of a tourism development planning process in Dong Van Karst Plateau Geopark in northern Vietnam. The results of the study highlight how understanding community resilience can be used to inform future tourism development efforts including infrastructure development, capacity building, and environment resource management.

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so)2–4. Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today’s grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss6 on millennial timescales will depend on bedrock topography and mantle viscosity—parameters that are difficult to measure and to incorporate into ice-sheet models. Radiocarbon dating of sediment cores and ice-penetrating radar observations are used to demonstrate that the West Antarctic Ice Sheet has not retreated progressively during the Holocene epoch, but has instead showed periods of retreat and re-advance.

The article discusses the history of firebombers, aerial firefighters which assist ground firefighters in controlling wildfires. The first successful use of an airplane was a converted 1939 Boeing 75 used by Willows Flying Service, which released 170 gallons of water in Mendocino National Forest in 1955. Topics include the 1954 Operation Firestop, a multi-agency collaborative effort to develop effective ways to battle wildfires in California; adding chemicals to water to avoid evaporation; and the motion picture "Always" featuring firebombers.

Non-communicable diseases (NCDs) in Africa have been comparatively neglected, partly due to donor-driven funding priorities. This is despite NCDs being the principal cause of mortality globally, with the majority incidence occurring in low-income and middle-income nations. Most of the patients with NCDs will suffer from pain, breathlessness and other physical symptoms, or need support with psychosocial or spiritual problems. Reflecting regional disease prevalence, late-stage clinical presentation, limited funding and restricted access to curative therapies, palliative care need in Africa is significantly high. Although palliative care provision has advanced significantly on the continent in the past decade, much of this development was driven by services for adult HIV patients. However, recent international and regional political declarations and commitments constitute a new global NCD agenda that calls for the integration of palliative care into the NCD response. This could be achieved under a chronic care model of service provision in partnership with other clinical providers in an integrated care continuum spanning prevention, early detection, diagnosis, treatment, survivorship and the end of life. Four important challenges have to be addressed if palliative care is to contribute meaningfully to this NCD agenda: (1) existing variation in the ability of countries to deal with NCDs per se; (2) ensuring clinical partners are integrated effectively with palliative care; (3) agreeing implementation is linked to relevant national-level and patient-level metrics; and (iv) underpinning palliative care and NCD care with a rigorous and locally relevant evidence base demonstrating appropriate, feasible and effective care.

Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewisx, a preferred binding receptor for PA. Notably, the levels of sialyl-Lewisxdirectly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewisxmodification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewisxin both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewisx, through a tumor necrosis factor (TNF)-α-mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewisxand anti-TNF-α attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewisx.

Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa(PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewisx, a preferred binding receptor for PA. Notably, the levels of sialyl-Lewisxdirectly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewisxmodification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewisxin both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewisx, through a tumor necrosis factor (TNF)-α-mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewisxand anti-TNF-α attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewisx.

Weekend admission is associated with higher in-hospital mortality than weekday admission. Whether providing enhanced weekend staffing for acute medical inpatient services reduces mortality or length of stay is unknownMethods This paper describes a retrospective analysis of in-hospital mortality and length of stay before and after introduction of an enhanced, consultant-led weekend service in acute medicine in November 2012. In-hospital mortality was compared for matching admission calendar months before and after introduction of the new service, adjusted for case volume. Length of stay and 30-day post-discharge mortality were also compared; illness severity of patients admitted was assessed by cross-sectional acuity audits.Results Admission numbers increased from 6,304 (November 2011–July 2012) to 7,382 (November 2012–July 2013), with no change in acuity score in elderly medical patients but a small fall in younger patients. At the same time, however, a 57% increase in early-warning score triggered calls was seen in 2013 (410 calls vs 262 calls in 2012; p<0.01). Seven-day consultant working was associated with a reduction in in-hospital mortality from 11.4% to 8.8% (p<0.001). Mortality within 30 days of discharge fell from 2.4% to 2.0% (p=0.12). Length of stay fell by 1.9 days (95% CI 1.1–2.7; p=0.004) for elderly medicine wards and by 1.7 days (95% CI 0.8–2.6; p=0.008) for medical wards. Weekend discharges increased from general medical wards (from 13.6% to 18.8%, p<0.001) but did not increase from elderly medicine wards.Conclusions Introduction of an enhanced, consultant-led model of working at weekends was associated with reduced in-hospital and 30-day post discharge mortality rates as well as reduced length of stay. These results require confirmation in rigorously designed prospective studies.

The article recounts the F6F-5K target drone that took off from Naval Air Station Point Mugu, California on August 16, 1956. It states that the flight was normal at first but the drone turned back toward the coast instead of going to the Pacific Missile Range. Details of the explosion of the rocket are discussed. Grumman F11F-1 Tiger's career as a first line fighter is also mentioned. INSET: TIGER VERSUS ITSELF.

The article reports on a 2013 study on the impact of pen size and soil enriched housing conditions on faecal glucocorticoid concentrations (GC) in the endangered pygmy rabbit. Chronic stress due to poor housing conditions may reportedly be responsible for poor fecundity. The article states that it is best for pygmy rabbits to have soil for digging burrows, and that pen size has little effect on stress hormones, except where limited space and/or absence of soil is linked with higher GC.

Goldfields extend for 300 km around the margin of the Archaean Witwatersrand Basin of South Africa associated with regional greenschist facies metamorphism and deformation. Metamorphic mineral assemblages involving pyrophyllite-chloritoid are associated with gold in all goldfields, reflecting low pressure and 300 to 400°C conditions, and indicating high geothermal gradients. The origin of Witwatersrand gold can be explained by metamorphic devolatilisation to generate auriferous fluids beneath and outside the Witwatersrand Basin, followed by passage of these fluids along large structures and into the Basin. In this model, generation of the fluid is a consequence of the transition to amphibolite facies of mafic rocks such as Archaean greenstone belts, as in . In a grain-by-grain scale devolatilisation process, the lower temperature minerals have released their H2O, CO2and H2S to form a metamorphic fluid which at the time of its formation has already dissolved gold from these unenriched rocks (say at the ∼2 ppb Au level). A substantial volume of auriferous fluid is inferred given that regional metamorphism is on the scale of thousands of cubic kilometres, all evolving a few per cent of fluid. In the model, this auriferous fluid migrated from the immediate source region along grain boundaries, then in shear zones, and into the Witwatersrand Supergroup via the major thrust faults adjacent to all goldfields. Once in the Supergroup, fluid migration was via bedding planes and especially unconformity surfaces, along cross-cutting faults, shear zones and reef packages. The few thicker shale units and especially the overlying Archaean Ventersdorp basalt pile acted as barriers to fluid flow and facilitated fluid focussing. Deposition of gold from this auriferous fluid occurred where there was abundant carbon and/or iron. The distribution of these two elements was pre-determined by sedimentary distribution, and diagenetic migration. Many bedding features were preserved or mimicked during the hydrothermal replacement process because the volumetric strain in most of the sequence was low. Critical to the success of the hydrothermal process in producing gold deposits were the widespread local concentrations of C and Fe on unconformity surfaces, the reef packages, the major thrust faults adjacent to each goldfield, source rocks of greenstone-like character that were once at (sub)-greenschist facies grade with assemblages that included chlorite–calcite–pyrite, and a regional metamorphic event of high geothermal gradient. Moreover, critical to the exposure and preservation of the goldfields has been the limited erosion of the Basin since the hydrothermal deposition of the gold. The metamorphic devolatilisation–hydrothermal replacement model predicts many features of Witwatersrand ores, and can explain quantitatively the origin of its ∼100 000 t gold endowment. Calculations suggest that there is adequate gold at background (2 ppb) levels in inferred source rocks to form the necessary auriferous hydrothermal fluids; in contrast, there appears to have been insufficient particulate gold to form a significant placer accumulation. Without a viable source region for detrital gold, and indeed no plausible sorting mechanism to produce such deposits, it would be unwise to accept a placer model.

Glacimarine dynamics and associated sedimentary processes are closely tied to glacial regime and reflect dominant climatic conditions. Quantitative measurements for subpolar glaciers, such as sediment yield, are limited especially near glacial termini where most sediment accumulates. Here we characterize the modern glacimarine environment, quantify sediment flux and yield, document landform genesis and hypothesize potential future behaviour of Kronebreen and Kongsvegen glaciers in inner Kongsfjorden, Svalbard. A minimum of 6.74x103g m–2d–1(at least 300 mm a–1) of glacimarine sediment is building a grounding-line fan via submarine stream discharge from Kronebreen. Average daily sediment flux to the ice-contact basin is recorded to be 2.6x103g m–2d–1or an average annual flux of 1.56x105g m–2a–1. We measure an average annual ice-contact sediment yield of 1.20x104tonnes km–2a–1associated with the rapid genesis of grounding-line landforms. With forecasted warming we expect meltwater volumes and sediment flux to increase. Grounding-line deposits may aggrade above water, tending to stabilize the terminus at least initially if the sediment is sufficient to counteract total terminus ablation. This would hold until either the glaciers next surge or climatic warming ablates the glaciers through surface melting.

Feline myeloma-related disorders (MRD) are rare neoplasms of plasma cells. The multistep transformation model of myeloma in humans is based on the premise that plasma cells undergo neoplastic transformation primarily within the intramedullary compartment and that over time they become poorly differentiated and metastasize to extramedullary locations. Historically, diagnostic criteria used for human multiple myeloma have been applied to the cat, with the assumption that feline MRD commonly arises in the intramedullary compartment. Our objectives were to describe the features of feline MRD confirmed by cytology, histopathology, histochemistry, and immunohistochemistry and to categorize these tumors. A priori hypotheses were 1) tumor category predicts survival and 2) cats with well-differentiated tumors commonly have extramedullary involvement in contrast to human myeloma patients. This multicenter, retrospective study identified 26 MRD cases. There was good agreement between histopathologic and cytologic tumor categorization. Histochemistry and immunohistochemistry were shown to be valuable adjunct tests in the diagnosis of MRD. Cats with well-differentiated tumors had increased median survival relative to those with poorly differentiated tumors (254 versus 14 days). We have reported that marked extramedullary involvement at initial clinical presentation is significantly more common in the cat than in human MRD patients. In this study, we demonstrate that cats with well-differentiated tumors more commonly have extramedullary involvement than human myeloma patients with well-differentiated tumors (90% versus 20%, P < 0.0002). These results contrast strongly with the human myeloma model of primary intramedullary neoplastic transformation and suggest that primary extramedullary neoplastic transformation may be more common in feline MRD.

A personal narrative is presented which explores the author's experience of gardening with neighbors.

Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.

Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a hereditary auto-inflammatory periodic fever syndrome associated with autosomal dominant ectodomain mutations in the 55kDa tumor necrosis factor receptor (TNFRSF1A). Over forty mutations in TNFRSF1A are associated with TRAPS. Plasma levels of soluble TNFRSF1A (sTNFRSF1A) are abnormally low in TRAPS patients, as is shedding of TNFRSF1A by some patients' leucocytes. It was hypothesised that a deficit in neutralisation of TNF by sTNFRSF1A in TRAPS might result in an increased sensitivity to the inflammatory effects of TNF. However, not all TRAPS-related TNFRSF1A mutations result in defective receptor shedding by leucocytes. We found that dermal fibroblasts, but not leucocytes, from TRAPS patients with C33Y mutation demonstrated reduced shedding of TNFRSF1A, and that shedding of both wild-type and mutant truncated TNFRSF1A from transfected cell lines was similar. It is unlikely that a defect in TNFRSF1A shedding fully explains the clinical features of TRAPS. We investigated the behaviour of TRAPS-related TNFRSF1A mutants compared with wildtype in transfected cell lines: the mutant forms of TNFRSF1A retained signalling functions, but showed abnormalities of intra-cellular trafficking and TNF binding suggestive of protein misfolding. The severity of the abnormalities were observed with different mutants correlated with the degree of penetrance and clinical severity. We hypothesise that aggregation and ligand-independent signalling of mutant TNFRSF1A may occur. The increased understanding of the genetic basis and pathophysiology of TRAPS has facilitated therapeutic advances in the clinical management of this condition, particularly the use of the TNF-neutralising agent etanercept.

During June 2003, a period of mid level discharge (17,400 m−3s−1), a parcel of water in the lower Mississippi River was sampled every 2 h during its 4-d transit from river km 362 near Baton Rouge to km 0 at Head of Passes, Louisiana, United States. Properties measured at the surface during each of the 48 stations were temperature, salinity, dissolved organic carbon (DOC), total dissolved nitrogen, dissolved macronutrients (NO3+NO2, PO4, Si(OH)4), chlorophylla(chla; three size fractions: < 5 μm, 5–20 μm, and > 20 μm) pigment composition by HPLC, total suspended matter (TSM), particulate organic carbon (POC), and particulate nitrogen (PN). Air-water CO2flux was calculated from surface water dissolved inorganic carbon and pH. During the 4 d transit, large particles appeared to be settling out of the surface water. Concentrations of chlacontaining particles > 20 μm declined 37%, TSM declined 43%, POC declined 42% and PN declined 57%. Concentrations of the smaller chlacontaining particles did not change suggesting only large particulate materials were settling. There was no measurable loss of dissolved NO3, PO4, or Si(OH)4, consistent with the observation that chladid not increase during the 4-d transit. DOC declined slightly (3%). These data indicate there was little autotrophic or heterotrophic activity in the lower Mississippi River at this time, but the system was slightly net heterotrophic.

Objective. To describe the effect of Etanercept treatment in systemic AA amyloidosis in tumour necrosis factor receptor-associated periodic syndrome (TRAPS).Methods. Etanercept therapy was given to a 27 year old woman, with systemic amyloidosis and nephrotic syndrome, and to her 51 year old father, also affected by TRAPS, who had previously undergone renal transplant for amyloidosis. Serum SAA levels, plasma cytokines, glomerular filtration rate and serum amyloid P scanning were monitored.Results. Etanercept treatment resulted in initial clinical resolution of nephrotic syndrome in the 27 year old female. Both subjects demonstrated improvements in GFR and initial reduction or stabilisation of amyloid deposits on SAP scanning.Conclusion. Etanercept may reverse or slow the progression of systemic AA amyloidosis in subjects with C33Y TNFRSF1A mutation. Treatment may however need to be continuous and life-long to prevent progression to end stage disease.

Several combinations of mix type, aggregate type, asphalt binder type, and layer thickness are in place at the National Center for Asphalt Technology (NCAT) test track. It was desirable to examine the effects these various combinations may have on temperatures within the pavement. The purpose of this study was to evaluate measured versus predicted temperatures, evaluate the effect of mix type on pavement temperature, and compare the effect of surface layer thickness on pavement temperatures. On the basis of temperature data from the NCAT test track, some of the general conclusions are that (a) both the Strategic Highway Research Program (SHRP) and Long-Term Pavement Performance (LTPP) temperature models slightly underpredicted high pavement temperatures at 50% reliability and slightly overpredicted temperatures at 98% reliability and (b) the low-temperature models for SHRP overpredicteded low pavement temperatures for both 50% and 98% reliability. The LTPP models were also overly conservative at 98% reliability. These results indicate that asphalt binders may not need to be as soft as specified in the Superpaver; performance grading system for low-temperature performance.

Several combinations of mix type, aggregate type, asphalt binder type, and layer thickness are in place at the National Center for Asphalt Technology (NCAT) test track. It was desirable to examine the effects these various combinations may have on temperatures within the pavement. The purpose of this study was to evaluate measured versus predicted temperatures, evaluate the effect of mix type on pavement temperature, and compare the effect of surface layer thickness on pavement temperatures. On the basis of temperature data from the NCAT test track, some of the general conclusions are that (a) both the Strategic Highway Research Program (SHRP) and Long-Term Pavement Performance (LTPP) temperature models slightly underpredicted high pavement temperatures at 50% reliability and slightly overpredicted temperatures at 98% reliability and (b) the low-temperature models for SHRP overpredicteded low pavement temperatures for both 50% and 98% reliability. The LTPP models were also overly conservative at 98% reliability. These results indicate that asphalt binders may not need to be as soft as specified in the Superpaver; performance grading system for low-temperature performance.

Human neutrophil α-defensins (HNPs) are small, cationic, Cys-rich antimicrobial proteins that play important roles in innate immunity against infectious microbes such as bacteria, fungi and enveloped viruses. Synthesized as inactive precursors in vivo (pre-proHNPs), HNPs are activated through proteolytic removal of the inhibitory pro-peptide required for subcellular sorting and correct folding. We seek to understand the molecular basis for the recognition between the 45-residue pro-peptide and the C-terminal functional domain. Here we described, total chemical synthesis of the 75-residue human neutrophil pro α-defensin-1 (proHNP1) via native chemical ligation. After oxidative folding, proHNP1 is cleaved by cyanogen bromide at the Met⁴⁵-Ala⁴⁶ peptide bond to release the mature form. The native disulfide connectivity in HNP1, i.e. Cys¹-Cys⁶, Cys²-Cys⁴ and Cys³-Cys⁵, is verified by mass mapping of peptide fragments generated by proteolytic digestion and Edman degradation. Fluorescence spectroscopy studies and antimicrobial activity assays further support that synthetic proHNP1 and HNP1 are correctly folded. While largely unstructured in aqueous solution, the pro-peptide binds to HNP1 intermolecularly with an apparent K_d value of 6.2 μmat pH 7.4, confirming the mode of intramolecular inactivation of human α-defensin precursors.

Objective. To assess the effects prospectively of tumour necrosis factor (TNF) receptor superfamily (TNFRSF) fusion proteins TNFRSF1B (etanercept) and TNFRSF1A (p55TNFr‐Ig) in patients with TNF receptor associated periodic syndrome (TRAPS).Methods. Seven patients with a clinical and genetic diagnosis of TRAPS received subcutaneous etanercept for 24 weeks. One of these patients had previously received an intravenous infusion of p55TNFr‐Ig. Therapeutic response was assessed by comparing corticosteroid requirement, acute‐phase response and an established scoring system over 20 weeks, both on and off etanercept.Results. Etanercept was well tolerated. The five corticosteroid‐responsive patients required significantly less corticosteroids and demonstrated reductions in acute‐phase reactants on etanercept. The two patients not requiring corticosteroids had small reductions in disease activity scores. The effect of p55TNFr‐Ig in a single patient with TRAPS remains unclear.Conclusions. Etanercept does not abolish inflammatory attacks but improves disease activity allowing corticosteroid reduction. Etanercept may be clinically useful in replacing or reducing steroid requirements in the treatment of TRAPS. A formal trial of etanercept to establish its role in clinical management is indicated.

An experimental facility has been constructed near the campus of Auburn University in Alabama for the purpose of conducting research to extend the lives of flexible pavements. Experimental sections on the 2.8-km Pavement Test Track are cooperatively funded by external sponsors, most commonly, state departments of transportation, with operation and research managed by the National Center for Asphalt Technology (NCAT). Forty-six different flexible pavements were installed at the facility, each at a length of 61 m. Materials and methods unique to the section sponsors were imported during construction to maximize the applicability of the results. A design lifetime of truck traffic is now being applied over a 2-year period, with field performance documented weekly. Sponsors typically compare the performance of two or more sections constructed with different materials or by different methods to obtain information that can be used to build future pavements with the greatest amount of rut resistance. In addition to assessing alternatives for sponsors, NCAT is responsible for guiding the overall effort in a direction that will address policy issues for the highway industry as a whole. Specifically, laboratory methods that have the potential to predict rutting when they are used before and during construction are being compared with field performance for every experimental mix so that the most suitable method(s) can be recommended. Results from loaded wheel testing are presented to encompass the empirical approach, while results from shear and creep testing facilitate mechanistic analyses. The success of each method will ultimately be measured by comparing the performance in the laboratory with the performance on the experimental roadway.

An experimental facility has been constructed near the campus of Auburn University in Alabama for the purpose of conducting research to extend the lives of flexible pavements. Experimental sections on the 2.8-km Pavement Test Track are cooperatively funded by external sponsors, most commonly, state departments of transportation, with operation and research managed by the National Center for Asphalt Technology (NCAT). Forty-six different flexible pavements were installed at the facility, each at a length of 61 m. Materials and methods unique to the section sponsors were imported during construction to maximize the applicability of the results. A design lifetime of truck traffic is now being applied over a 2-year period, with field performance documented weekly. Sponsors typically compare the performance of two or more sections constructed with different materials or by different methods to obtain information that can be used to build future pavements with the greatest amount of rut resistance. In addition to assessing alternatives for sponsors, NCAT is responsible for guiding the overall effort in a direction that will address policy issues for the highway industry as a whole. Specifically, laboratory methods that have the potential to predict rutting when they are used before and during construction are being compared with field performance for every experimental mix so that the most suitable method(s) can be recommended. Results from loaded wheel testing are presented to encompass the empirical approach, while results from shear and creep testing facilitate mechanistic analyses. The success of each method will ultimately be measured by comparing the performance in the laboratory with the performance on the experimental roadway.

A magnetic resonance imaging (MRI) tubular rheometer for polymer melt systems is described. This technique allows the viscosity to be determined over a range of shear rates. It relies upon obtaining steady-state velocity profiles in tubular pipes using MRI and simultaneously measuring the pressure drop. In these experiments, the shear viscosity of a low-density polyethylene (LDPE) melt was measured at shear rates between 1.8 and 12.1 s^-1 and was found to be approximately 117.7 Pa·s. The viscosity was also determined using a parallel plate rheometer in which it was found to vary slightly with shear rate, ranging from 113.9 to 107.2 Pa·s, comparing favorably with the MRI determined values. MRI is noninvasive and nondestructive and can be applied to opaque systems; hence, it has the potential to be used for in-process monitoring.

Chitosan is a derivative of chitin, extracted from the exoskeleton of lobsters, crabs and shrimps. As a semi-permeable biological dressing, it maintains a sterile wound exudate beneath a dry scab, preventing dehydration and contamination of the wound to optimise conditions for healing. In this study, evaluation of healing at split skin graft donor sites, dressed half with chitosan and half with a conventional dressing, showed that chitosan facilitated rapid wound re-epithelialisation and the regeneration of nerves within a vascular dermis. In addition, digital colour separation analysis of donor site scars demonstrated an earlier return to normal skin colour at chitosan-treated areas.

Background. Cyclosporin and tacrolimus are immunomodulatory drugs which act predominantly on T cells. Improvements in certain manifestations, particularly skin tightness, have been observed in a number of patients with scleroderma treated with these drugs. However, to date there have been no reports of their use in a routine clinical setting.
Methods. Patients attending clinical immunology clinics who had progressive systemic sclerosis and related syndromes and who had received cyclosporin and/or tacrolimus were identified. Details of their treatment, including drug dosage, duration of and response to treatment, side-effects and reasons for withdrawal, were recorded.
Results. Sixteen patients had been given cyclosporin and 13 of these had been treated for skin tightness. Half noticed significant softening of their skin whilst on treatment, and resolution was observed in all four of the patients treated for digital vasculitis. Side-effects were common and dose-limiting, and contributed to withdrawal in 12 out of 13 patients. Eight patients had been treated with tacrolimus; two of these had stopped the drug because of progression of their disease, one developed diarrhoea, prompting withdrawal, one stopped tacrolimus following improvement, and four remained on the drug. Side-effects had occurred in three patients.
Conclusion. Improvements in skin occur in approximately half of all cases of scleroderma treated with either cyclosporin or tacrolimus, suggesting a beneficial effect. Side-effects, especially hypertension, are common with cyclosporin and often necessitate withdrawal. Adverse effects are also observed with tacrolimus, but in the small cohort so far treated only one patient had stopped the drug for this reason.

Immunity against the carbohydrate components of microorganisms mediated by antibodies is an important part of host defenses. Humans and closely related primates, but not other mammals, possess natural anti-Galalpha1-3Gal antibodies which also, although less avidly, react with melibiose (Galalpha1-6Glc). Using an enzyme-linked immunosorbent assay (ELISA) with melibiose-bovine serum albumin as an antigen, we analyzed bovine anti-alpha galactosyl antibodies with respect to specificity and distribution in individual animals. Inhibition assays showed that melibiose was the strongest inhibitor, followed equally by stachyose (Galalpha1-6Galalpha1-6Glcbeta1-2Fru) and raffinose (Galalpha1-6Glcbeta1-2Fru) and then by Galbeta1-6Gal, Gal, and Galalpha1-2Gal. Others, including Galalpha1-3Gal and Galalpha1-4Gal, only exhibited minor inhibition. Thus, these bovine anti-alpha galactosyl antibodies appeared to preferentially react with Galalpha1-6Glc or Galalpha1-6Gal. The distinction of this specificity from that (Galalpha1-3Gal) of human antibodies was further demonstrated by the poor reaction of bovine serum to the Galalpha1-3Gal antigen in comparison to human serum. All 27 healthy bovine serum samples of the three age groups (newborn, calf, and adult) tested contained such antibodies with titers increasing with age. The antibodies purified by affinity chromatography using a melibiose-agarose column were mainly of the immunoglobulin G (IgG) isotype with a concentration of >23 microg/ml in most samples. IgG1 was found to be the primary antimelibiose IgG isotype in all age groups by isotype-specific ELISA, but a significant increase in IgG2, an isotype more related to innate immunity, was observed in calves and adults, compared to newborns. The purified antibodies reacted with the type II bovine strain of Streptococcus agalactiae, a common pathogen of bovine mastitis. Thus, these anti-Galalpha1-6Glc or Galalpha1-6Gal antibodies in cattle might be involved in defense against microbes bearing this or the related epitopes.

Abstract: A small Holocene fan is forming where Queen Inlet, a hanging valley, enters West Arm fjord, Glacier Bay, Alaska. Queen fan formed in the last 80 years following retreat of the Little Ice Age glacier that filled Glacier Bay about 200 yr BP. It was built mainly by a turbidite system originating from Carroll Glacier delta, as the delta formed in the early 1900s at the head of Queen Inlet. The Late Holocene Queen fan is comparable to large Pleistocene fans that formed in the Gulf of Alaska and differs from trough-mouth fans formed by cooler climate glacier systems.