Epidermal Langerhans Cells are Dispensable for Humoral and Cell-Mediated Immunity Elicited by Gene Gun Immunization.

Gene gun immunization, i.e., bombardment of skin with DNA-coated particles, is an efficient method for the administration of DNA vaccines. Direct transfection of APC or cross-presentation of exogenous Ag acquired from transfected nonimmune cells enables MHC-I-restricted activation of CD8(+) T cells. Additionally, MHC-II-restricted presentation of exogenous Ag activates CD4(+) Th cells. Being the principal APC in the epidermis, Langerhans cells (LC) seem ideal candidates to accomplish these functions. However, the dependence on LC of gene gun-induced immune reactions has not yet been demonstrated directly. This was primarily hampered by difficulties to discriminate the contributions of LC from those of other dermal dendritic cells. To address this problem, we have used Langerin-diphtheria toxin receptor knockin mice that allow for selective inducible ablation of LC. LC deficiency, even over the entire duration of experiments, did not affect any of the gene gun-induced immune functions examined, including proliferation of CD4(+) and CD8(+) T cells, IFN-gamma secretion by spleen cells, Ab production, CTL activity, and development of protective antitumor immunity.

Langerin(+) Dermal Dendritic Cells Are Critical for CD8(+) T Cell Activation and IgH gamma-1 Class Switching in Response to Gene Gun Vaccines

The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-gamma producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation. The Journal of Immunology, 2011, 186: 1377-1383.

Belfast Legion for Improvised Sights and Sounds

Improvisations, Centro Mexicano para la Mu´sica y las Artes Sonoras, Morelia

Silica grain labelling and EDX spectroscopy; evidence for inter-grain diffusion of Pt(NH3)(4)(2+) species during Pt/SiO2 catalyst preparation by ionic exchange

Labelling of silica grains and energy dispersive X-ray spectroscopy (EDX) in a TEM-FEG (field emission gun) were used to demonstrate the migration of Pt(NH3)(4)(2+) species from one grain to another during Pt/SiO2 catalyst preparation by the ion-exchange procedure.

Efficient modelling and optimisation of hybrid multilayered plates subject to ballistic impact

Among the key challenges present in the modelling and optimisation of composite structures against impact is the computational expense involved in setting up accurate simulations of the impact event and then performing the iterations required to optimise the designs. It is of more interest to find good designs given the limitations of the resources and time available rather than the best possible design. In this paper, low cost but sufficiently accurate finite element (FE) models were generated in LS Dyna for several experimentally characterised materials by semi-automating the modelling process and using existing material models. These models were then used by an optimisation algorithm to generate new hybrid offspring, leading to minimum weight and/or cost designs from a selection of isotropic metals, polymers and orthotropic fibre-reinforced laminates that countered a specified impact threat. Experimental validation of the optimal designs thus identified was then successfully carried out using a single stage gas gun. With sufficient computational hardware, the techniques developed in this pilot study can further utilise fine meshes, equations of state and sophisticated material models, so that optimal hybrid systems can be identified from a wide range of materials, designs and threats.

Report of the workshop for life detection in samples from Mars

The question of whether there is or was life on Mars has been one of the most pivotal since Schiaparellis' telescopic observations of the red planet. With the advent of the space age, this question can be addressed directly by exploring the surface of Mars and by bringing samples to Earth for analysis. The latter, however, is not free of problems. Life can be found virtually everywhere on Earth. Hence the potential for contaminating the Mars samples and compromising their scientific integrity is not negligible. Conversely, if life is present in samples from Mars, this may represent a potential source of extraterrestrial biological contamination for Earth. A range of measures and policies, collectively termed ‘planetary protection’, are employed to minimise risks and thereby prevent undesirable consequences for the terrestrial biosphere. This report documents discussions and conclusions from a workshop held in 2012, which followed a public conference focused on current capabilities for performing life-detection studies on Mars samples. The workshop focused on the evaluation of Mars samples that would maximise scientific productivity and inform decision making in the context of planetary protection. Workshop participants developed a strong consensus that the same measurements could be employed to effectively inform both science and planetary protection, when applied in the context of two competing hypotheses: 1) that there is no detectable life in the samples; or 2) that there is martian life in the samples. Participants then outlined a sequence for sample processing and defined analytical methods that would test these hypotheses. They also identified critical developments to enable the analysis of samples from Mars.

The Political Economy of Swift's Satires and other Prose Works

Jonathan Swift wrote perceptively about the emerging commercial society
in Britain in the early eighteenth century. His particular focus was on the
financial revolution and its implications for economic and political stability
as well as for shifts of power between the landed and commercial
classes. Following his return to Ireland Swift’s focus shifted to the developmental
problems of his native country. In several pamphlets he advocated
consumption of domestic products, challenged existing political
structures and made trenchant criticisms of absenteeism and other dysfunctional
aspects of the land tenure system. Swift’s politico-economic
concerns are fully reflected in his best known work, Gulliver’s Travels but
his most pointed criticism of the emerging commercial system is contained
in A Modest Proposal. Written in the form of an economic pamphlet, A
Modest Proposal is ostensibly designed to address the problem of poverty
in Ireland. In addition to its implicit criticism of economic policy in Ireland,
the pamphlet challenges the separation of economics and morality as
evidenced in the writings of William Petty and Bernard Mandeville. Swift
parodies Petty’s political arithmetic but it is suggested here that he also
had in his sights the consequentialist reasoning present in the work of
both authors but explicitly so in Mandeville.
Keywords: financial revolution, public debt, paper credit, rationality, political
arithmetic, consequentialism, Petty (William), Mandeville (Bernard)

Mitochondrial DNA Damage Following Isolated Muscle Exercise: A Preliminary Investigation Into HO-1 Gene Expression

PURPOSE: This preliminary investigation was designed to test the hypothesis that high intensity single-leg exercise can cause extensive cell DNA damage, which subsequently may affect the expression of the HO-1 gene. METHODS: Six (n=6) apparently healthy male participants (age 27 + 7 yrs, stature 174 + 12 cm, body mass 79 + 4 kg and BMI 24 + 4 kg/m2) completed 100 isolated and continuous maximal concentric contractions (minimum force = 200 N, speed of contraction = 60°/sec) of the rectus femoris muscle. Using a spring-loaded and reusable Magnum biopsy gun with a 16-gauge core disposable biopsy needle, skeletal muscle micro biopsy tissue samples were extracted at rest and following exercise. mRNA gene expression was determined via two-step quantitative real-time PCR using GAPDH as a reference gene. RESULTS: The average muscle force production was 379 + 179 N. High intensity exercise increased mitochondrial 8-OHdG concentration (P < 0.05 vs. rest) with a concomitant decrease in total antioxidant capacity (P < 0.05 vs. rest). Exercise also increased protein oxidation as quantified by protein carbonyl concentration (P < 0.05 vs. rest). HO-1 expression increased (> 2-fold change vs. rest) following exercise, and it is postulated that this change was not significant due to low subject numbers (P > 0.05). CONCLUSION: These preliminary findings tentatively suggest that maximal concentric muscle contractions can cause intracellular DNA damage with no apparent disruption to the expression of the antioxidant stress protein HO-1. Moreover, it is likely that cell oxidant stress is required to activate the signal transduction cascade related to the expression of HO-1. A large-scale study incorporating a greater subject number is warranted to fully elucidate this relationship.

Concussion and Brain Injury in Contact Sport: Legal Implications

A concussed participant leaving the field of play is one of the most worrying sights in sport. It is also one that might have serious legal implications for sports governing bodies. Over the past number of years, a major class action suit has rumbled through the US courts as taken against that country's biggest professional sport, the National Football League. The NFL is at present attempting to settle the lawsuit from more than 4,500 retired players who claim that the NFL knew for decades about the chronic health risks associated with cumulative concussions in American football but failed to warn players or take preventative steps. Testimony from retired NFL players has revealed stories of chronic headaches, Alzheimer-like forgetfulness, altered personalities and sometimes a downward spiral into depression, violence and suicide. Medical research is suggesting that professional American football players are three times more likely to die as a result of certain neurodegenerative diseases than the general population. This paper notes that the concerns about concussion are not confined to the NFL and extend to contact sport more widely and notably rugby union. This paper also assesses the reaction of leading sports governing bodies globally to the recorded medical risks and accompanying legal vulnerabilities.

Polarized skylight does not calibrate the compass system of a migratory bat

In a recent study, Greif et al. (2014) demonstrated a functional role of polarized light for a bat species confronted with a homing task. These non-migratory bats appeared to calibrate their magnetic compass by using polarized skylight at dusk, yet it is unknown if migratory bats also use these cues for calibration. During autumn migration, we equipped Nathusius' bats, Pipistrellus nathusii, with radio transmitters and tested if experimental animals exposed to a 90° rotated band of polarized light during dusk, would head in a different direction compared with control animals. After release, bats of both groups continued their journey in the same direction. This observation argues against the use of a polarization-calibrated magnetic compass by this migratory bat and questions that the ability of using polarized light for navigation is a consistent feature in bats. This finding matches with observations in some passerine birds that used polarized light for calibration of their magnetic compass before but not during migration.

Beneath an Irish Sky:A new play by Kieran Kelly

A fictionalised account of one Letterkenny man's journey, questioning what made him pick up a gun to fight for his country and how one moment in his youth affected the rest of his life. Part of the 'Ireland 2016 Centenary Programme'

Direct spun aligned carbon nanotube web-reinforced proton exchange membranes for fuel cells

A new method combining electrospinning of SPEEK and direct spinning of CNT forests has been used to prepare sulfonated poly(ether ether ketone) (SPEEK)/directly spinnable carbon nanotube (dsCNT) composite proton exchange membranes. The SPEEK/dsCNT membrane is more robust than SPEEK alone, and in a fuel cell significantly outperforms both SPEEK and the commercial Nafion 212 membranes.