Identifying cell class specific losses from serially generated electroretinogram components

Purpose. Processing of information through the cellular layers of the retina occurs in a serial manner. In the electroretinogram (ERG), this complicates interpretation of inner retinal changes as dysfunction may arise from "upstream" neurons or may indicate a direct loss to that neural generator. We propose an approach that addresses this issue by defining ERG gain relationships.

Methods. Regression analyses between two serial ERG parameters in a control cohort of rats are used to define gain relationships. These gains are then applied to two models of retinal disease.

Results. The PIIIamp to PIIamp gain is unity whereas the PIIamp to pSTRamp and PIIamp to nSTRamp gains are greater than unity, indicating "amplification" (P <0.05). Timing relationships show amplification between PIIIit to PIIit and compression for PIIit to pSTRit and PIIit to nSTRit, (P <0.05). Application of these gains to ?-3-deficiency indicates that all timing changes are downstream of photoreceptor changes, but a direct pSTR amplitude loss occurs (P <0.05). Application to diabetes indicates widespread inner retinal dysfunction which cannot be attributed to outer retinal changes (P <0.05).

Conclusions. This simple approach aids in the interpretation of inner retinal ERG changes by taking into account gain characteristics found between successive ERG components of normal animals.

‘A dance for all the outcasts’: Class and Postcolonialism in Brendan Behan’s An Giall and The Hostage

As Susan Bassnett and Harish Trivedi argue, ‘translation does not happen in a vacuum, but in a continuum; it is not an isolated act, it is part of an ongoing process of intercultural transfer’. In understanding Brendan Behan's most celebrated and controversial translation, of his spare Irish language play An Giall (1958) to its riotous English counterpart The Hostage (1958), understanding the problematic ‘intercultural transfer’ between British and Irish life in the 1950s is crucial. Comparisons between both works reveal significant changes that illuminate Behan's relationship with both nations and provide a sometimes oblique metacommentary regarding his most pressing political and personal anxieties. Yet for all their differences, the plays also share a common desire to transcend the divisions forged by the colonial experience through critical understandings of life on either side of the Irish Sea. In this essay, I argue that Behan's act of transculturation reveals a great deal more reflexivity and depth than many of his critics would allow, developing an iconoclastic dialogue between British and Irish mid-century life.

Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii

Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 µM against Gram-negative Escherichia coli, 4.3 µM against Gram-positive Staphylococcus aureus and 4–9 µM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6 %) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.

Family, state, class and solidarity: re-conceptualising intergenerational solidarity through the grounded theory approach

The relationship between class and intergenerational solidarities in the public and private spheres calls for further conceptual and theoretical development. This article discusses the findings from the first wave of a qualitative longitudinal study entitled Changing Generations, conducted in Ireland in 2011–2012, comprising 100 in-depth interviews with men and women across the age and socioeconomic spectrums. Constructivist grounded theory analysis of the data gives rise to the following postulates: (1) intergenerational solidarity at the family level is strongly contoured by socioeconomic status (SES); (2) intergenerational solidarity evolves as family generations observe each others’ practices and adjust their expectations accordingly; (3) intergenerational solidarity within families is also shaped by the public sphere (the welfare state) that generates varying expectations and levels of solidarity regarding State supports for different age groups, again largely dependent on SES; (4) the liberal welfare state context, especially at a time of economic crisis, enhances the significance of intergenerational solidarity within families. We conclude by calling for research that is attuned to age/generation, gender and class, and how these operate across the family and societal levels.

The Great Recession and the changing distribution of economic vulnerability by social class:The Irish case

Ireland provides an interesting case study of the distributional consequences of the Great Recession. To explore such effects we develop a measure of economic vulnerability based on a multidimensional risk profile for income poverty, material deprivation and economic stress. In the context of conflicting expectations of trends in social class differentials, we provide a comparison of pre and post-recession periods. Our analysis reveals a doubling of levels of economic vulnerability and a significant change in multidimensional profiles. Income poverty became less closely associated with material deprivation and economic stress and the degree of polarization between vulnerable and non-vulnerable classes was significantly reduced. Economic vulnerability is highly stratified by social class for both pre and post-recession periods. Focusing on absolute change, the main contrast is between the salariat and the non-agricultural self-employed and the remaining classes; providing some support for notions of polarization. In terms of relative change the higher salariat, the non-agricultural self-employed, the semi-unskilled manual and those who never worked gained relative to the remaining classes. This provides support the notion of ‘middle class squeeze’. The changing relationship between social class and household work intensity reflected a similar pattern. The impact of the latter on economic vulnerability declined sharply, while it came to play an increasing role in mediating the impact of membership of the non-agricultural middle classes. Responding to the political pressures likely to be associated with ‘middle class squeeze’ while sustaining the social welfare arrangements that have traditionally protected the economically vulnerable presents formidable challenges in terms of maintaining social cohesion and political legitimacy.

Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data

Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature.

Unveiling Fairness for the Consumer:The Law, Economics and Justice of Expanded Arbitration

In recent years, the US Supreme Court has rather controversially extended the ambit of the Federal Arbitration Act to extend arbitration’s reach into, inter alia¸ consumer matters, with the consequence that consumers are often (and unbeknownst to them) denied remedies which would otherwise be available. Such denied remedies include recourse to class action proceedings, effective denial of punitive damages, access to discovery and the ability to resolve the matter in a convenient forum.

The court’s extension of arbitration’s ambit is controversial. Attempts to overturn this extension have been made in Congress, but to no avail. In contrast to American law, European consumer law looks at pre-dispute agreements to arbitrate directed at consumers with extreme suspicion, and does so on the grounds of fairness. In contrast, some argue that pre-dispute agreements in consumer (and employment) matters are consumer welfare enhancing: they decrease the costs of doing business, which is then passed on to the consumer. This Article examines these latter claims from both an economic and normative perspective.

The economic analysis of these arguments shows that their assumptions do not hold. Rather than being productive of consumer surplus, the use of arbitration is likely to have the opposite effect. The industries from which the recent Supreme Court cases originated not only do not exhibit the industrial structure assumed by the proponents of expanded arbitration, but are also industries which exhibit features that facilitate consumer welfare reducing collusion.

The normative analysis addresses the fairness concerns. It is explicitly based upon John Rawls’ notion of “justice as fairness,” which can provide a lens to evaluate social institutions. This Rawlsian analysis considers the use of extended arbitration in consumer matters in the light of the earlier economic results. It suggests that the asymmetries present in the contractual allocation of rights serve as prima facie evidence that such arbitration–induced exclusions are prima facie unjust/unfair. However, as asymmetry is only a prima facie test, a generalized criticism of the arbitration exclusions (of the sort found in Congress and underlying the European regime) is overbroad.

Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin B₂-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B₂-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10⁻⁶ M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10⁻¹¹ M and 10⁻⁵ M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B₁- (desArg-HOE140) and B₂-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B₂-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B₂-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

A 2.2 GHz High-Efficiency Third-Harmonic-Peaking Class-EF Power Amplifier

This paper presents the design and implementation of a low-voltage-stress Class-EF power amplifier (PA) with extended maximum operating frequency, named as ‘third-harmonic-peaking Class-EF PA’. A novel transmission-line load network is proposed to meet the Class-EF impedance requirements at the fundamental, all even harmonics, and third harmonic components. It also provides an impedance matching to a 50 Ω load. A more effective λ/8 open- and shorted-stub network is deployed at the drain of the transistor replacing the traditional λ/4 transmission line. Implemented using GaN HEMTs, the PA delivered 39.2 dBm output power with 80.5% drain efficiency and 71% PAE at 2.22 GHz.