XBP1s levels are implicated in the biology and outcome of myeloma mediating different clinical outcomes to thalidomide-based treatments.

Immunoglobulin production by myeloma plasma cells depends on the unfolded protein response for protein production and folding. Recent studies have highlighted the importance of IRE1alpha and X box binding protein 1 (XBP1), key members of this pathway, in normal B-plasma cell development. We have determined the gene expression levels of IRE1alpha, XBP1, XBP1UNSPLICED (XBP1u), and XBP1SPLICED (XBP1s) in a series of patients with myeloma and correlated findings with clinical outcome. We show that IRE1alpha and XBP1 are highly expressed and that patients with low XBP1s/u ratios have a significantly better overall survival. XBP1s is an independent prognostic marker and can be used with beta2 microglobulin and t(4;14) to identify a group of patients with a poor outcome. Furthermore, we show the beneficial therapeutic effects of thalidomide in patients with low XBP1s/u ratios. This study highlights the importance of XBP1 in myeloma and its significance as an independent prognostic marker and as a predictor of thalidomide response.

Commentary on International Copyright Act 1886

The Act enabling the British government to become a signatory to the Berne Convention, which Convention came into force on 5 December 1887. The commentary describes the nature and extent of British participation in the three conferences which led to the signing of the Berne Convention, against a backdrop of several unsuccessful attempts to reform and consolidate the British copyright regime, the importance of pursuing meaningful Anglo-American copyright negotiations, and the significance of imperial-colonial copyright relations. The commentary also explores the extent to which the cause of Irish Nationalism, and the case for Home Rule, dominated the political landscape in early 1886, so explaining why the opportunity of adhering to the Berne Convention did not also lead to substantive reform of the domestic copyright regime at this time.

Avoiding Overfitting in Inverse Modeling of Chloride Migration in Concrete

Inverse analysis for reactive transport of chlorides through concrete in the presence of electric field is presented. The model is solved using MATLAB’s built-in solvers “pdepe.m” and “ode15s.m”. The results from the model are compared with experimental measurements from accelerated migration test and a function representing the lack of fit is formed. This function is optimised with respect to varying amount of key parameters defining the model. Levenberg-Marquardt trust-region optimisation approach is employed. The paper presents a method by which the degree of inter-dependency between parameters and sensitivity (significance) of each parameter towards model predictions can be studied on models with or without clearly defined governing equations. Eigen value analysis of the Hessian matrix was employed to investigate and avoid over-parametrisation in inverse analysis. We investigated simultaneous fitting of parameters for diffusivity, chloride binding as defined by Freundlich isotherm (thermodynamic) and binding rate (kinetic parameter). Fitting of more than 2 parameters, simultaneously, demonstrates a high degree of parameter inter-dependency. This finding is significant as mathematical models for representing chloride transport rely on several parameters for each mode of transport (i.e., diffusivity, binding, etc.), which combined may lead to unreliable simultaneous estimation of parameters.

Compensating Irish female revolutionaries, 1916-1923

The newly released Irish Military Service Pensions Collection offers the most comprehensive opportunity to examine the role of women in the Irish revolution (1916-1923) or in any comparable nationalist revolution. It is also an extremely useful source of evidence for an emerging historiographical trend of tracing the post-revolutionary lives of female veterans by examining the award of service pensions to them by that state. This article will examine the role played by gender in the award of such pensions, the economic and financial significance of them in a state that had under-developed welfare provision and the importance of them as a symbolic recognition of women’s roles in helping to achieve Irish independence. It also compares the post-conflict experience of Irish female revolutionary veterans with women who were involved in comparable international military conflicts.