In situ study of sigma phase formation in Cr-Co-Ni ternary alloys at 800°C using the long duration experiment facility at Diamond Light Source.

The new long duration experiment facility on beamline I11 at Diamond Light Source has been used to study the kinetics of sigma phase formation in three Cr-Co-Ni alloys. Diffraction data acquired during in situ exposure at 800°C for 50 d showed progressive increases in the sigma fraction. This was accompanied by changes in the proportions of the other phases, which differed markedly between the alloys studied. These results demonstrate the capabilities of the long duration facility for the study of metallurgical phenomena over periods of months to years, a capability not previously available at a synchrotron source.

Atmospheric transport of trace elements and nutrients to the oceans.

This paper reviews atmospheric inputs of trace elements and nutrients to the oceans in the context of the GEOTRACES programme and provides new data from two Atlantic GEOTRACES cruises. We consider the deposition of nitrogen to the oceans, which is now dominated by anthropogenic emissions, the deposition of mineral dust and related trace elements, and the deposition of other trace elements which have a mixture of anthropogenic and dust sources. We then consider the solubility (as a surrogate for bioavailability) of the various elements. We consider briefly the sources, atmospheric transport and transformations of these elements and how this results in strong spatial deposition gradients. Solubility of the trace elements also varies systematically between elements, reflecting their sources and cycling, and for some trace elements there are also systematic gradients in solubility related to dust loading. Together, these effects create strong spatial gradients in the inputs of bioavailable trace elements to the oceans, and we are only just beginning to understand how these affect ocean biogeochemistry.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

Trace element and isotope deposition across the air-sea interface: progress and research needs.

The importance of the atmospheric deposition of biologically essential trace elements, especially iron, is widely recognized, as are the difficulties of accurately quantifying the rates of trace element wet and dry deposition and their fractional solubility. This paper summarizes some of the recent progress in this field, particularly that driven by the GEOTRACES, and other, international research programmes. The utility and limitations of models used to estimate atmospheric deposition flux, for example, from the surface ocean distribution of tracers such as dissolved aluminium, are discussed and a relatively new technique for quantifying atmospheric deposition using the short-lived radionuclide beryllium-7 is highlighted. It is proposed that this field will advance more rapidly by using a multi-tracer approach, and that aerosol deposition models should be ground-truthed against observed aerosol concentration data. It is also important to improve our understanding of the mechanisms and rates that control the fractional solubility of these tracers. Aerosol provenance and chemistry (humidity, acidity and organic ligand characteristics) play important roles in governing tracer solubility. Many of these factors are likely to be influenced by changes in atmospheric composition in the future. Intercalibration exercises for aerosol chemistry and fractional solubility are an essential component of the GEOTRACES programme.This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

Past, Present and Future Atmospheric Nitrogen Deposition.

Reactive nitrogen emissions into the atmosphere are increasing due to human activities, affecting nitrogen deposition to the surface and impacting the productivity of terrestrial and marine ecosystems. An atmospheric chemistry-transport model (TM4-ECPL) is here used to calculate the global distribution of total nitrogen deposition, accounting for the first time for both its inorganic and organic fractions in gaseous and particulate phases, and past and projected changes due to anthropogenic activities. The anthropogenic and biomass burning ACCMIP historical and RCP6.0 and RCP8.5 emissions scenarios are used. Accounting for organic nitrogen (ON) primary emissions, the present-day global nitrogen atmospheric source is about 60% anthropogenic, while total N deposition increases by about 20% relative to simulations without ON primary emissions. About 20-25% of total deposited N is ON. About 10% of the emitted nitrogen oxides are deposited as ON instead of inorganic nitrogen (IN) as is considered in most global models. Almost a 3-fold increase over land (2-fold over the ocean) has been calculated for soluble N deposition due to human activities from 1850 to present. The investigated projections indicate significant changes in the regional distribution of N deposition and chemical composition, with reduced compounds gaining importance relative to oxidized ones, but very small changes in the global total flux. Sensitivity simulations quantify uncertainties due to the investigated model parameterizations of IN partitioning onto aerosols and of N chemically fixed on organics to be within 10% for the total soluble N deposition and between 25-35% for the dissolved ON deposition. Larger uncertainties are associated with N emissions.

The cycling of organic nitrogen through the atmosphere.

Atmospheric organic nitrogen (ON) appears to be a ubiquitous but poorly understood component of the atmospheric nitrogen deposition flux. Here, we focus on the ON components that dominate deposition and do not consider reactive atmospheric gases containing ON such as peroxyacyl nitrates that are important in atmospheric nitrogen transport, but are probably not particularly important in deposition. We first review the approaches to the analysis and characterization of atmospheric ON. We then briefly summarize the available data on the concentrations of ON in both aerosols and rainwater from around the world, and the limited information available on its chemical characterization. This evidence clearly shows that atmospheric aerosol and rainwater ON is a complex mixture of material from multiple sources. This synthesis of available information is then used to try and identify some of the important sources of this material, in particular, if it is of predominantly natural or anthropogenic origin. Finally, we suggest that the flux of ON is about 25 per cent of the total nitrogen deposition flux.

Determination of total and non-water soluble iodine in atmospheric aerosols by thermal extraction and spectrometric detection (TESI).

Iodine has recently been of interest in atmospheric chemistry due to its role in tropospheric ozone depletion, modification of the HO/HO(2) ratio and aerosol nucleation. Gas-phase iodine chemistry is tightly coupled to the aerosol phase through heterogeneous reactions, which are dependent on iodine concentrations and speciation in the aerosol. To date, the only method available for total iodine determination in aerosols is collection on filters by impaction and quantification by neutron activation analysis (NAA). NAA is not widely available to all working groups and is costly to commission. Here, we present a method to determine total iodine concentrations in aerosol impact filter samples by combustion of filter sub-samples (approximately 5 cm(2)) at 1,000 degrees C, trapping in deionised water and quantification by UV/Vis spectroscopy. Both quartz and cellulose filters were analysed from four separate sampling campaigns. The method proved to be sensitive (3sigma = 6 ng absolute iodine approximately 3 pmol m(-3)) precise (RSD approximately 5%) and accurate, as determined by external and standard addition calibrations. Total iodine concentrations ranged from 10 pmol m(-3) over the Southern Ocean to 100 pmol m(-3) over the tropical Atlantic, in agreement with previous estimates. The soluble iodine concentration (extracted with water and measured by ICP-MS) was then subtracted from the total iodine to yield non-water-soluble iodine (NSI). The NSI fraction ranged from 20% to 53% of total iodine, and thus can be significant in some cases.

Anaesthesia for endoscopic sinus surgery.

Endoscopic sinus surgery is commonly performed and has a low risk of major complications. Intraoperative bleeding impairs surgical conditions and increases the risk of complications. Remifentanil appears to produce better surgical conditions than other opioid analgesics, and total intravenous anaesthesia with propofol may provide superior conditions to a volatile-based technique. Moderate hypotension with intraoperative beta blockade is associated with better operating conditions than when vasodilating agents are used. Tight control of CO(2) does not affect the surgical view. The use of a laryngeal mask may be associated with improved surgical conditions and a smoother emergence. It provides airway protection equivalent to that provided by an endotracheal tube in well-selected patients, but offers less protection from gastric regurgitation. Post-operatively, multimodal oral analgesia provides good pain relief, while long-acting local anaesthetics have been shown not to improve analgesia.

Pdcd4 repression of lysyl oxidase inhibits hypoxia-induced breast cancer cell invasion.

Metastasis to bone, liver and lungs is the primary cause of death in breast cancer patients. Our studies have revealed that the novel tumor suppressor Pdcd4 inhibits breast cancer cell migration and invasion in vitro. Loss of Pdcd4 in human nonmetastatic breast cancer cells increased the expression of lysyl oxidase (LOX) mRNA. LOX is a hypoxia-inducible amine oxidase, the activity of which enhances breast cancer cell invasion in vitro and in vivo. Specific inhibition of LOX activity by beta-aminopropionitrile or small interfering RNA decreased the invasiveness of T47D and MCF7 breast cancer cells attenuated for Pdcd4 function. Most significantly, loss of Pdcd4 augments hypoxia induction of LOX as well. Conversely, overexpression of Pdcd4 significantly reversed the hypoxia induction of LOX expression in T47D cells attenuated for Pdcd4. However, Pdcd4 did not affect hypoxia-inducible factor-1 (HIF-1) protein expression or HIF-1-responsive element-luciferase activity in response to hypoxia, suggesting that Pdcd4 regulation of LOX occurs through an HIF-independent mechanism. Nevertheless, the loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness.

DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue.

CONTEXT: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY(1-36)) which is truncated by DPP-IV to NPY(3-36), as a consequence NPY's affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. AIMS: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). METHODS: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean +/- s.d.) +/- 5 kg/m2, age: 43.7 +/- 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1-100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. RESULTS AND CONCLUSION: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean +/- s.e.) +/- 37 micromol/l; NPY, 100 nM: 161 +/- 27 micromol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 +/- 14 micromol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 +/- 6 signal units (SU)] vs. lean subjects (186 +/- 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 +/- 111 SU vs. lean: 711 +/- 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors.

Epicardial adipose tissue as a source of nuclear factor-kappaB and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease.

CONTEXT: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. OBJECTIVES: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. DESIGN: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. RESULTS: Western blotting showed epicardial AT had significantly higher NFkappaB, inhibitory-kappaB kinase (IKK)-gamma, IKKbeta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P<0.05]. CONCLUSION: Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

Impacts of atmospheric anthropogenic nitrogen on the open ocean.

Increasing quantities of atmospheric anthropogenic fixed nitrogen entering the open ocean could account for up to about a third of the ocean's external (nonrecycled) nitrogen supply and up to approximately 3% of the annual new marine biological production, approximately 0.3 petagram of carbon per year. This input could account for the production of up to approximately 1.6 teragrams of nitrous oxide (N2O) per year. Although approximately 10% of the ocean's drawdown of atmospheric anthropogenic carbon dioxide may result from this atmospheric nitrogen fertilization, leading to a decrease in radiative forcing, up to about two-thirds of this amount may be offset by the increase in N2O emissions. The effects of increasing atmospheric nitrogen deposition are expected to continue to grow in the future.

Accuracy of dilution of morphine for intrathecal use.

Morphine is administered intrathecally alone or in combination with other drugs to provide spinal analgesia. Dose-finding studies have recommended 100 microg be used intrathecally to optimise analgesia and minimise side-effects for caesarean section and hip replacement surgery. Dilute solutions of morphine are generally not available, mandating preparation from a 10 mg/ml ampoule. We postulated that diluting morphine would be inaccurate and imprecise, contributing to the variability in patient response often reported. Twenty consultant and trainee anaesthetists were recruited and asked to prepare 100 microg of morphine from 10 mg/ml vials and from a hypothetical prediluted 500 microg/ml solution. The resultant samples were analysed using liquid chromatography. Prepared morphine doses ranged from 25 microg to 289 microg. Dilution of morphine was less accurate (P = 0.001) and more imprecise (P = 0.001) compared with using a prediluted solution. A single-step dilution technique using 0.1 ml of a solution diluted to 1.0 mg/ml was more accurate than when a double-dilution technique was used (P = 0.047). Given that dose-finding studies suggest that analgesia and side-effects vary at the dose range found in this study, we advocate the use of prediluted solutions. If dilution is to be performed a single-step dilution technique should be used.

Copper and zinc removal from aqueous solution by mixed mineral systems II. The role of solution composition and aging.

This study investigates Cu and Zn removal onto binary mixed mineral sorbents from simulated wastewater, relevant to streams impacted by acid mine drainage and effluents. Mixed suspensions of kaolinite/montmorillonite and kaolinite/goethite exhibited different sorption behavior from the single mineral components, reducing Cu and Zn removal (except Cu sorbed on montmorillonite/goethite) over the range of pH investigated. Cu and Zn removal by the electrolyzed systems showed a complex response to increased ionic strength, which increased solid concentration, leading to lower Cu and Zn sorption. Enhanced Cu sorption on the montmorillonite/goethite as age increased may be attributed to increased hydroxylation of the mineral surface resulting in the formation of new reactive sites.

Copper and zinc removal from aqueous solution by mixed mineral systems I. Reactivity and removal kinetics.

This study investigates the reactivity and removal kinetics of Cu and Zn onto mixed mineral systems from aqueous solution related to acid mine drainage impacted areas. The sorbents used were kaolinite, Al-montmorillonite, goethite, and their mixtures. The effects of surface charge, proton coefficient, and sorption kinetics were studied at room temperature (23+/-2 degrees C). Using an empirical model, mineral mixing reduced the exchange of protons for sorbing ions and the acidity of the reactive sites, thus impeding Cu and Zn removal by proton exchange. Based on the amount of Cu and Zn sorbed on the mixed mineral suspensions at ionic strength 0.01 to 0.1 M and pH 4, it is suggested that Cu and Zn removal from aqueous solution was by both inner and outer sphere complexation. Mineral mixing reduced the transfer rate of Cu relative to the single mineral suspensions in both slow and fast reaction phases. The behavior of the mixed suspensions in Cu and Zn sorption suggest that different reactive sites were involved at the onset of sorption, becoming similar to those of the single mineral components over time.

Global iron connections between desert dust, ocean biogeochemistry, and climate.

The environmental conditions of Earth, including the climate, are determined by physical, chemical, biological, and human interactions that transform and transport materials and energy. This is the "Earth system": a highly complex entity characterized by multiple nonlinear responses and thresholds, with linkages between disparate components. One important part of this system is the iron cycle, in which iron-containing soil dust is transported from land through the atmosphere to the oceans, affecting ocean biogeochemistry and hence having feedback effects on climate and dust production. Here we review the key components of this cycle, identifying critical uncertainties and priorities for future research.

Homotypic variation of canine flexor tendons: implications for the design of experimental studies in animal models.

Water, collagen and glycosamimoglycan contents, cross-sectional area, stiffness and elastic modulus were carefully quantitated in flexor digitorum superficialis tendons from mature canines. From these data the within- and between-animal variability was estimated and used to demonstrate sample size calculations for both two-group and paired (within-animal) study designs. The estimated between-dog variance was typically 50% or less of the total variance for the parameters investigated. In other words, the correlation among the tendons within an animal for most measures was not strong. Therefore, for some variables (e.g., elastic modulus) in this animal and tendon model, there is no appreciable gain in statistical power by using a paired study design. A two-group design could be used, but any within-animal correlation must be accounted for in the analysis. For other variables such as collagen content, a paired design would gain substantial power.

Reaction of carbon monoxide with the reduced active site of bacterial nitric oxide reductase.

Bacterial nitric oxide reductase (NOR), a member of the superfamily of heme-copper oxidases, catalyzes the two-electron reduction of nitric oxide to nitrous oxide. The key feature that distinguishes NOR from the typical heme-copper oxidases is the elemental composition of the dinuclear center, which contains non-heme iron (FeB) rather than copper (CuB). UV-vis electronic absorption and room-temperature magnetic circular dichroism (RT-MCD) spectroscopies showed that CO binds to Fe(II) heme b3 to yield a low-spin six-coordinate species. Photolysis of the Fe(II)-CO bond is followed by CO recombination (k(on) = 1.7 x 10(8) M(-1) x s(-1)) that is approximately 3 orders of magnitude faster than CO recombination to the active site of typical heme-copper oxidases (k(on) = 7 x 10(4) M(-1)x s(-1)). This rapid rate of CO recombination suggests an unimpeded pathway to the active site that may account for the enzyme's high affinity for substrate, essential for maintaining denitrification at low concentrations of NO. In contrast, the initial binding of CO to reduced heme b3 measured by stopped-flow spectroscopy is much slower (k(on) = 1.2 x 10(5) M(-1) x s(-1)). This suggests that an existing heme distal ligand (water/OH-) may be displaced to elicit the spin-state change observed in the RT-MCD spectrum.

In vivo measurement of solute transport rates in a bioartificial organ.

A radioactive tracer technique was used to evaluate the in vivo mass transfer properties of a tissue engineered bioartificial organ. To obtain these measurements, bioartificial organs were first implanted in ten rats and allowed to vascularize for 4 weeks. After vascularization, radioactive inulin was placed within the cell chamber of the device. Following the addition of tracer, blood samples were taken over a 4-h time period and inulin levels were determined. The results of these experiments were interpreted using a compartmental model that describes the transport of inulin from the cell chamber, across the immunoisolation membrane, and into the neovascularized region contained within the adjacent scaffold material. Nonlinear regression analysis of the plasma inulin levels using a four-compartment pharmacokinetic model provided estimates of the membrane permeability, the product of the capillary wall surface area and capillary permeability, and the glomerular filtration rate (GFR). The permeability of the membrane was found to be 3.50 x 10(-5) +/- 1.15 x 10(-5) cm/sec (95% confidence interval, n = 10), which compares favorably to previous in vitro permeability data for this membrane. The capillary wall permeability was found to be 0. 0087 6 0.0029 cm(3)/sec/100 g of tissue. This compares well to a reported value for inulin of 0.01 cm(3)/sec/100 g of tissue. The GFR was found to be 0.44 +/- 0.07 ml/h/g BW, which compares well with a reported value of 0.40 ml/hr/g BW. The inulin tracer technique reported here is a useful tool for assessing the in vivo transport characteristics of a bioartificial organ as well as the vascularization within tissue engineered structures.

Management of symptomatic malignant melanoma of the gastrointestinal tract.

BACKGROUND: Melanoma metastatic to the gastrointestinal (GI) tract is asymptomatic or presents with pain, bleeding, or obstruction. To determine whether surgery influences outcomes, we reviewed our experience with this patient population. METHODS: Medical records of patients with metastatic melanoma to the GI tract were reviewed. Patients were divided into four groups, i.e., complete resection, partial debulking, unresectable, or unexplored. Analysis was performed using the Kaplan-Meier method. RESULTS: Fifty patients with melanoma metastatic to the GI tract were identified (40 men and 10 women; mean age, 44 years). Presenting symptoms included pain (62%), bleeding (28%), and obstruction (18%). Diagnosis was confirmed using contrast studies (38%), endoscopy (20%), or computed tomography (30%). Thirty-six patients (61%) underwent a total of 39 operations. Seventeen patients underwent complete resection, whereas 14 underwent partial debulking. Five patients had unresectable lesions, and 14 patients did not undergo exploration because of medical contraindications. The operative mortality rate was 2.5% (1 of 39). The mean survival times for the unexplored and unresected groups were similar (4.1 months). Patients who underwent partial resection exhibited a longer mean survival time (8.9 months) than did patients in the unresected group (P < .001). The complete-resection group demonstrated a mean survival time of 23.5 months, which was significantly longer than that for patients who underwent less than complete resection (P < .0001). CONCLUSIONS: Metastatic melanoma to the GI tract can result in significant morbidity and death. Surgical resection can be performed safely. Patients for whom all sites of disease are completely resected experience significant improvements in survival times, compared with patients who undergo less than complete resection. For selected patients, surgical treatment of metastatic melanoma involving the GI tract is appropriate therapy.