Commentary: Totally Tubular - Northern Science's Most Excellent Adventure

... The second day of our meetings revisited [the] theme of northern science "going down the tubes." One of us, ... cautioned against too dim a view of the state of our interest. "While it's undeniable that northern science is going down the tubes, as my colleagues suggests," he said, "I think it is also important to realize that some of those tubes are directing us towards some pretty interesting places - increased interdisciplinary work and greater relevance to the northern community itself are two trends which the current funding levels are forcing us to consider as we seek to legitimate our proposed research. These are not, I think, such bad directions to see our activities descend to" .... My goal here ... is to discuss more fully some of the current trajectories of the journey of northern science and suggest that in thinking "tubular" about the trip we can find ourselves in a most excellent adventure. Northern research, primarily due to its geographic isolation and associated costs, has long relied on a multidisciplinary approach. ... The second feature of northern research that has been sustained to some degree over the years has been the extent to which local populations have been involved as critical participants in the research. In the early years of poor communications and logistical staging, native northerners often made the difference in the success or failure of a project - at times their guidance, food, habitations and local knowledge quite literally made a difference between life and death. As state intervention in the North increased, aboriginal people became more marginalized in their participation, but the symbiotic heritage remained. It is partly for this reason that the current recognition of the potential for traditional knowledge to contribute to scientific research has been taken most seriously in the North. ... A good many northern scientists look back on the 1960s and '70s as the halcyon days of northern research, a time when there was seemingly inexhaustible funding and access to logistical support. ... That the reports of public inquiries, along with a downturn in world petroleum prices, effectively ended the grand schemes of these interests and their associated research should demonstrate pretty clearly the relationship between science and the business community. This is a relationship that many of us assume without a second thought; why then the trepidation displayed at the prospect of greater involvement of wider local community interest in research? These are not just academic issues of informed debate for this journal and our conference libations; they are critical to the emergence of a legitimate indigenous northern scholarly tradition and that role that northern-oriented academics are going to play in it. ..

The relation between adsorption isotherm shapes and the mechanism of some vapour phase and solution adsorption processes

The aim of this work was to determine the mechanisms involved in several adsorption systems from a consideration of the isotherms obtained. The problem of atmospheric pollution is first considered Sulphur dioxide and smoke (which can, be considered as being similar to a low temperature industrial carbon black) are two, of the most common pollutants occurring in city atmospheres. They are shown to act together in producing pollution problem the carbon acting as a carrier for adsorbed sulphur dioxide. In winter smoke adsorbs more sulphur dioxide than in summer due to the lower average temperature. Adsorption of the sulphur dioxide on the carbon accentuates the corrosion of metals and building stones containing calcium carbonate probably after catalytic oxidation of the sulphur dioxide to sulphuric acid. The corrosion of iron can be considered an electrolytic action, the metal acting as the anode, the sulphuric acid as the electrolyte and the carbon as carrier, bridge and cathode. Stones containing calcium or magnesium carbonate are attacked by sulphuric acid. When calcium and magnesium carbonates are converted to their respective sulphates the volume Increases are 1.7 and 4 times, causing exfoliation of the stone. Plants are affected physically by the blockage of their stomata by cartoon or chemically by destruction of their essential nutrients in the soil toy sulphuric acid. Section II deals with adsorption of solutes from solution. In Part I the adsorption of a range of basic dyes on alkaline alumina powder is considered. By comparing the surface area of the powder with the amount of dyes adsorbed, the latter are seen to be adsorbed as cationic micelles with the exception of Rhodamine B and 6GB, which, because of their molecular geometry favour adsorption as monomeric ions with a vertical edge on orientation. This is confirmed by the shape of the isotherm: "L" and types for micellar adsorption and "S" type for end-on orientation. Dyes adsorbed as micelles by ion-exchange can be desorbed completely with water or a similarly charged solute, whereas potential hydrogen bonding dyes such as Rhodamine 6GB are only partially removed by rinsing. All the basic dyes which are apparently adsorbed as large cationic micelles exhibit an anomalous (endothermic) adsorption attributable to the breakdown of micelles in solution to reform into larger micelles at the surface, probably with a different structure. An energy diagram is given to explain endothermic adsorption. Safranine T appears to favour edge-on orientation to give a monolayer at high temperature, and the disaggregation of this dye with increased temperature is studied spectroscopically. The relationship between the ratio of the . two (x, y hand) peaks and the logarithin of the temperature is linear. The plot of log, coverage factor (apparent surface area for each dye / "true" surface area) against the log, cationic weight of the dyes is linear and the line obtained is coincident with similar lines for the same dyes on graphite and formalin fixed yeast cells. Other adsorption systems: examined include phenol on chitin and also on varieties of rubber, p-nitrophenol on silica, and a mordant dye on alumina; the results are discussed in the light of the general principles of solution adsorption

Intra-session and inter-day reliability of the Myon 320 electromyography system during sub-maximal contractions

Electromyography systems are widely used within the field of scientific and clinical practices. The reliability of these systems are paramount when conducting research. The reliability of Myon 320 Surface Electromyography System is yet to be determined. This study aims to determine the intra-session and inter-day reliability of the Myon 320 Surface Electromyography System. Muscle activity from fifteen participants was measured at the anterior deltoid muscle during a bilateral front raise exercise, the vastus lateralis muscle during a squat exercise and the extensor carpi radialis brevis (ECRB) muscle during an isometric handgrip task. Intra-session and inter-day reliability was calculated by intraclass correlation coefficient, standard error of measurement and coefficient of variation (CV). The normalized root mean squared (RMS) surface electromyographic signals produced good intra-session and inter-day testing intraclass correlation coefficient values (range: 0.63-0.97) together with low standard error of measurement (range: 1.49-2.32) and CV (range: 95% Confidence Interval = 0.36-12.71) measures for the dynamic-and-isometric contractions. The findings indicate that the Myon 320 Surface Electromyography System produces good to fair reliability when examining intra-session and inter-day reliability. Findings of the study provide evidence of the reliability of electromyography between trials which is essential during clinical testing.</p

Brazing development and interfacial metallurgy study of tungsten and copper joints with eutectic gold copper brazing alloy

Current proposals for the divertor component of a thermonuclear fusion reactor include tungsten and copper as potentially suitable materials. This paper presents the procedures developed for the successful brazing of tungsten to oxygen free high conductivity (OFHC) copper using a fusion appropriate gold based brazing alloy, Orobraze 890 (Au80Cu20). The objectives were to develop preparation techniques and brazing procedures in order to produce a repeatable, defect free butt joint for tungsten to copper. Multiple brazing methods were utilised and brazing parameters altered to achieve the best joint possible. Successful and unsuccessful brazed specimens were sectioned and analysed using optical and scanning electron microscopy, EDX analysis and ultrasonic evaluation. It has been determined that brazing with Au80Cu20 has the potential to be a suitable joining method for a tungsten to copper joint

Continual trials spontaneous recognition tasks in mice: reducing animal numbers and improving our understanding of the mechanisms underlying memory

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioural noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioural noise and thus significantly reduces the numbers of rats required to retain statistical power. Here we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognise object-location combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use

Perirhinal cortex and the recognition of relative familiarity

Spontaneous object recognition (SOR) is a widely used task of recognition memory in rodents which relies on their propensity to explore novel (or relatively novel) objects. Network models typically define perirhinal cortex as a region required for recognition of previously seen objects largely based on findings that lesions or inactivations of this area produce SOR deficits. However, relatively little is understood about the relationship between the activity of cells in the perirhinal cortex that signal novelty and familiarity and the behavioural responses of animals in the SOR task. Previous studies have used objects that are either highly familiar or absolutely novel, but everyday memory is for objects that sit on a spectrum of familiarity which includes objects that have been seen only a few times, or objects that are similar to objects which have been previously experienced. We present two studies that explore cellular activity (through c-fos imaging) within perirhinal cortex of rats performing SOR where the familiarity of objects has been manipulated. Despite robust recognition memory performance, we show no significant changes in perirhinal activity related to the level of familiarity of the objects. Reasons for this lack of familiarity-related modulation in perirhinal cortex activity are discussed. The current findings support emerging evidence that perirhinal responses to novelty are complex and that task demands are critical to the involvement of perirhinal cortex in the control of object recognition memory

Modulation of blood-brain barrier permeability by neutrophils: in vitro and in vivo studies

The blood-brain barrier (BBB) restricts solute permeability across healthy cerebral endothelial cells. However, during inflammation, permeability is increased and can lead to deleterious cerebral edema. Neutrophils are early cellular participants in acute inflammation, but their effect on BBB permeability is unclear. To study this, neutrophils were applied in a resting and activated state to in vitro and in vivo models of the BBB. In vitro, human neutrophils (5 × 106/ml) were activated with tumor necrosis factor (100U/ml) and leukotriene B4 (10-7mol/l). Untreated neutrophils reduced permeability across the human brain endothelial cell line hCMEC/D3. Activated neutrophils returned permeability to baseline, an effect blocked by the reactive oxygen scavengers superoxide dismutase (10U/ml) and catalase (1000U/ml). In vivo, human neutrophils (2.5 × 105 in 4μl) were injected into the striatum of anesthetized juvenile Wistar rats, and BBB permeability measured 30 minutes later. This was compared to control injections (4μl) of vehicle (0.9% saline) and arachidonic acid (10-3mol/l). The injection generated a small hematoma around the injection tract (<3μl). Untreated neutrophils induced significantly lower permeability in their vicinity than activated neutrophils, with a trend to lowered permeability compared to the vehicle control. Neither untreated nor activated neutrophils induced permeability increases, while arachidonic acid increased permeability as a positive control. This study further delineates the effect of neutrophils on the BBB, and demonstrates that resting neutrophils induce acute reductions in permeability while activated neutrophils have a neutral effect. The in vivo model reiterates some aspects of acute intracerebral hemorrhage

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan.

The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes