Solid state image sensor research Final technical report

Fifty-element linear arrays of InAs photodiode

Leukotriene B4 stimulates the release of arachidonate in human neutrophils via the action of cytosolic phospholipase A2

AbstractLeukotriene B4 (LTB4) is a potent lipid mediator of inflammation and is involved in the receptor-mediated activation of a number of leukocyte responses including degranulation, superoxide formation, and chemotaxis. In the present research, stimulation of unprimed polymorphonuclear leukocytes (neutrophils) with LTB4 results in the transient release of arachidonate as measured by mass. This release of arachidonate was maximal at an LTB4 concentration of 50–75 nM and peaked at 45 s after stimulation with LTB4. The transient nature of this release can be attributed, in part, to a fast (<60 s) metabolism of the added LTB4. Moreover, the inhibition of the reacylation of the released arachidonate with thimerosal results in greater than 4-times as much arachidonate released. Thus, a rapid reacylation of the released arachidonate also contributes to the transient nature of its measured release. Multiple additions of LTB4, which would be expected to more closely resemble the situation in vivo where the cell may come into contact with an environment where LTB4 is in near constant supply, yielded a more sustained release of arachidonate. No release of [3H]arachidonate was observed when using [3H]arachidonate-labeled cells. This indicates that the release of arachidonate as measured by mass is most probably the result of hydrolysis of arachidonate-containing phosphatidylethanolamine within the cell since the radiolabeled arachidonate is almost exclusively incorporated into phosphatidylcholine and phosphatidylinositol pools under the non-equilibrium radiolabeling conditions used. Consistent with the role of cytosolic phospholipase A2 (cPLA2) in the release of arachidonate, potent inhibition of the LTB4-stimulated release was observed with methylarachidonylfluorophosphonate, an inhibitor of cPLA2 (IC50 of 1 μM). The bromoenol lactone of the calcium-independent phosphospholipase A2. failed to affect LTB4-stimulated release of arachidonate in these cells

Inhibition of Immune Complex-Induced Inflammation by A small Molecular Weight Selectin Antagonist

The anti-inflammatory effect of a small molecular weight antagonist of P- and E-selectin-dependent cell adhesion was examined. The glycolipid sulphatide was shown to block the adherence of thrombin-activated rat platelets to HL-60 cells. This interaction is known to be dependent on P-selectin. The rat dermal reverse passive Arthus reaction was used to assess the effect of sulphatide on a neutrophil dependent inflammatory response. Sulphatide dosedependently blocked both the vascular permeability increase and cell infiltration after intraperitoneal administration. These results show that a small molecular weight compound which blocks P- and E-selectin dependent adhesion in vitro can effectively block the inflammation due to immune complex deposition. A compound with this type of profile may have therapeutic potential in the treatment of immune complex mediated diseases

Best practice fleet management and priority actions

This paper reviews relevant literature and publicly available fleet management programs, along with workplace road safety policies and procedures. Discussions were also held with managers of selected companies about their fleet safety achievements. This work identified key vehicle and driver safety interventions from the literature, plus best practice fleet management and workplace road safety policies and priority actions for consideration within fleets. Managers reported progress in organisational acceptance and recognition that road trauma is a social, human, financial, reputation, efficiency and operational risk to an organisation and needs to be given priority at all management levels. The study investigated workplace safety management principles and their application in road safety management. Within standard management processes, companies wishing to reduce their road safety risk should: reassess the need for travel; reorganise work journeys to reduce exposure to risk or use lower risk journey options; invest in the upfront safety quality of vehicles that are being used; and engage their staff and stakeholders about risk management on the road.Small, M., Bailey, T., Lydon, M., & Davern, T.http://www.rsrpe2013.com.au/conference-papers/conference-papers.ph

Detection and quantification of γ-H2AX using a dissociation enhanced lanthanide fluorescence immunoassay

Phosphorylation of the histone protein H2AX to form γ-H2AX foci directly represents DNA double-strand break formation. Traditional γ-H2AX detection involves counting individual foci within individual nuclei. The novelty of this work is the application of a time-resolved fluorescence assay using dissociation-enhanced lanthanide fluorescence immunoassay for quantitative measurements of γ-H2AX. For comparison, standard fluorescence detection was employed and analyzed either by bulk fluorescent measurements or by direct foci counting using BioTek Spot Count algorithm and Gen 5 software. Etoposide induced DNA damage in A549 carcinoma cells was compared across all test platforms. Time resolved fluorescence detection of europium as a chelated complex enabled quantitative measurement of γ-H2AX foci with nanomolar resolution. Comparative bulk fluorescent signals achieved only micromolar sensitivity. Lanthanide based immunodetection of γ-H2AX offers superior detection and a user-friendly workflow. These approaches have the potential to improve screening of compounds that either enhance DNA damage or protect against its deleterious effects

Australia and Other Nations are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward

BACKGROUND: Australia has joined a growing number of nations which have evaluated the physical activity and sedentary behaviour status of their children. Australia received a 'D minus' in the first Active Healthy Kids Australia Physical Activity Report Card. METHODS: An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer three questions: 1) What are the main sedentary behaviours of children?, 2) What are the potential mechanisms for sedentary behaviour to impact on child health and development? and, 3) What are the effects of different types of sedentary behaviours on child health and development? RESULTS: Neither sedentary time nor screen time are homogeneous activities likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviours may positively or negatively affect cardiometabolic, neuro-musculoskeletal, and psycho-social health, though the strength of evidence varies. National surveillance systems, and mechanistic, longitudinal and experimental studies are needed for Australia and other nations to improve their grade. CONCLUSIONS: Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviours are critical to the healthy growth, development and wellbeing of children. Nations therefore need strategies to address these common behaviours

Genes Influencing Circadian Differences in Blood Pressure in Hypertensive Mice

Essential hypertension is a common multifactorial heritable condition in which increased sympathetic outflow from the central nervous system is involved in the elevation in blood pressure (BP), as well as the exaggerated morning surge in BP that is a risk factor for myocardial infarction and stroke in hypertensive patients. The Schlager BPH/2J mouse is a genetic model of hypertension in which increased sympathetic outflow from the hypothalamus has an important etiological role in the elevation of BP. Schlager hypertensive mice exhibit a large variation in BP between the active and inactive periods of the day, and also show a morning surge in BP. To investigate the genes responsible for the circadian variation in BP in hypertension, hypothalamic tissue was collected from BPH/2J and normotensive BPN/3J mice at the ‘peak’ (n = 12) and ‘trough’ (n = 6) of diurnal BP. Using Affymetrix GeneChip® Mouse Gene 1.0 ST Arrays, validation by quantitative real-time PCR and a statistical method that adjusted for clock genes, we identified 212 hypothalamic genes whose expression differed between ‘peak’ and ‘trough’ BP in the hypertensive strain. These included genes with known roles in BP regulation, such as vasopressin, oxytocin and thyrotropin releasing hormone, as well as genes not recognized previously as regulators of BP, including chemokine (C-C motif) ligand 19, hypocretin and zinc finger and BTB domain containing 16. Gene ontology analysis showed an enrichment of terms for inflammatory response, mitochondrial proton-transporting ATP synthase complex, structural constituent of ribosome, amongst others. In conclusion, we have identified genes whose expression differs between the peak and trough of 24-hour circadian BP in BPH/2J mice, pointing to mechanisms responsible for diurnal variation in BP. The findings may assist in the elucidation of the mechanism for the morning surge in BP in essential hypertension

Parents speak : what are their perceptions of their children’s experiences in a 90/10 one-way language immersion program?

Dual Language programs can be found across the globe and they offer learners opportunities to become immersed in a new language. The purpose of my study was to investigate parents’ perceptions of their children’s experiences in a one-way 90/10 dual language program that began in elementary school and has continued into secondary school. I interviewed ten parents whose children are currently involved with dual language at the secondary level and asked them to share their experiences and insights on programmatic features as well as areas of concern that schools in the program may need to address. I aimed to examine parents’ understanding of the experiences that their child has had over time and the programmatic features parents favor that prompted them to extend their child’s continued participation into the secondary level. I found that parents valued outcomes the program generated, including preparing their child to be a global citizen, enabling them to achieve content mastery, and encouraging them to take responsibility and become independent. Parents also identified challenges with their child maintaining engagement with the adopted language along the way, primarily during transitions from elementary to middle and middle to high school. In analyzing my findings, I examined how the concept of self-interest related to parent decision-making. I hope that the results of my study will allow school and district leaders, like myself, to consider approaches to enhance the structural aspects of a dual language program already in operation

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72563/1/j.1365-2893.2005.00581.x.pd

Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress

The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 +/- 4 mmHg for AT(1A)R vs 10 +/- 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 +/- 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress