Home in British working-class fiction

Offering new readings of working-class writing that focus on the home as a key emotional and material site in writing by working-class authors from the Edwardian period through to the mid-1990s. With close readings of The Ragged Trousered Philanthropists, works by D. H. Lawrence, Ethel Carnie Holdsworth, Ellen Wilkinson, Lewis Grassic Gibbon, Walter Brierley, Alan Sillitoe, John Braine, Nell Dunn, Sam Selvon, Sid Chaplin, Buchi Emecheta, Pat Barker, Jeanette Winterson, James Kelman and many others. The book demonstrates the importance of ideas of home and its narrative representation to the making and expression of class feeling and identity.

Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts

Aims. Protein kinases are potential therapeutic targets for heart failure, but most studies of cardiac protein kinases derive from other systems, an approach that fails to account for specific kinases expressed in the heart and the contractile cardiomyocytes. We aimed to define the cardiomyocyte kinome (i.e. the protein kinases expressed in cardiomyocytes) and identify kinases with altered expression in human failing hearts. Methods and Results. Expression profiling (Affymetrix microarrays) detected >400 protein kinase mRNAs in rat neonatal ventricular myocytes (NVMs) and/or adult ventricular myocytes (AVMs), 32 and 93 of which were significantly upregulated or downregulated (>2-fold), respectively, in AVMs. Data for AGC family members were validated by qPCR. Proteomics analysis identified >180 cardiomyocyte protein kinases, with high relative expression of mitogen-activated protein kinase cascades and other known cardiomyocyte kinases (e.g. CAMKs, cAMP-dependent protein kinase). Other kinases are poorly-investigated (e.g. Slk, Stk24, Oxsr1). Expression of Akt1/2/3, BRaf, ERK1/2, Map2k1, Map3k8, Map4k4, MST1/3, p38-MAPK, PKCδ, Pkn2, Ripk1/2, Tnni3k and Zak was confirmed by immunoblotting. Relative to total protein, Map3k8 and Tnni3k were upregulated in AVMs vs NVMs. Microarray data for human hearts demonstrated variation in kinome expression that may influence responses to kinase inhibitor therapies. Furthermore, some kinases were upregulated (e.g. NRK, JAK2, STK38L) or downregulated (e.g. MAP2K1, IRAK1, STK40) in human failing hearts. Conclusions. This characterization of the spectrum of kinases expressed in cardiomyocytes and the heart (cardiomyocyte and cardiac kinomes) identified novel kinases, some of which are differentially expressed in failing human hearts and could serve as potential therapeutic targets.

Disorder prediction methods, their applicability to different protein targets and their usefulness for guiding experimental studies

The role and function of a given protein is dependent on its structure. In recent years, however, numerous studies have highlighted the importance of unstructured, or disordered regions in governing a protein’s function. Disordered proteins have been found to play important roles in pivotal cellular functions, such as DNA binding and signalling cascades. Studying proteins with extended disordered regions is often problematic as they can be challenging to express, purify and crystallise. This means that interpretable experimental data on protein disorder is hard to generate. As a result, predictive computational tools have been developed with the aim of predicting the level and location of disorder within a protein. Currently, over 60 prediction servers exist, utilizing different methods for classifying disorder and different training sets. Here we review several good performing, publicly available prediction methods, comparing their application and discussing how disorder prediction servers can be used to aid the experimental solution of protein structure. The use of disorder prediction methods allows us to adopt a more targeted approach to experimental studies by accurately identifying the boundaries of ordered protein domains so that they may be investigated separately, thereby increasing the likelihood of their successful experimental solution.

Direct and ozone-mediated forcing of the Southern Annular Mode by greenhouse gases

We assess the roles of long-lived greenhouse gases and ozone depletion in driving meridional surface pressure gradients in the southern extratropics; these gradients are a defining feature of the Southern Annular Mode. Stratospheric ozone depletion is thought to have caused a strengthening of this mode during summer, with increasing long-lived greenhouse gases playing a secondary role. Using a coupled atmosphere-ocean chemistry-climate model, we show that there is cancelation between the direct, radiative effect of increasing greenhouse gases by the also substantial indirect—chemical and dynamical—feedbacks that greenhouse gases have via their impact on ozone. This sensitivity of the mode to greenhouse gas-induced ozone changes suggests that a consistent implementation of ozone changes due to long-lived greenhouse gases in climate models benefits the simulation of this important aspect of Southern Hemisphere climate.

The influence of sea ice dynamics on the climate sensitivity and memory to increased Antarctic sea ice

The study analyzes the sensitivity and memory of the Southern Hemisphere coupled climate system to increased Antarctic sea ice (ASI), taking into account the persistence of the sea ice maxima in the current climate. The mechanisms involved in restoring the climate balance under two sets of experiments, which differ in regard to their sea ice models, are discussed. The experiments are perturbed with extremes of ASI and integrated for 10 yr in a large 30-member ensemble. The results show that an ASI maximum is able to persist for ; 4 yr in the current climate, followed by a negative sea ice phase. The sea ice insulating effect during the positive phase reduces heat fluxes south of 60 8 S, while at the same time these are intensified at the sea ice edge. The increased air stability over the sea ice field strengthens the polar cell while the baroclinicity increases at midlatitudes. The mean sea level pressure is reduced (increased) over high latitudes (midlatitudes), typical of the southern annular mode (SAM) positive phase. The Southern Ocean (SO) becomes colder and fresher as the sea ice melts mainly through sea ice lateral melting, the consequence of which is an increase in the ocean stability by buoyancy and mixing changes. The climate sensitivity is triggered by the sea ice insulating process and the resulting freshwater pulse (fast response), while the climate equilibrium is restored by the heat stored in the SO subsurface layers (long response). It is concluded that the time needed for the ASI anomaly to be dissipated and/or melted is shortened by the sea ice dynamical processes.

Fighting merchants

Selected essays from a conference held in November 2013 to celebrate the contribution to scholarship of the medieval historian Professor James L. Bolton.

Control of nanomaterial self-assembly in ultrasonically levitated droplets

We demonstrate that acoustic trapping can be used to levitate and manipulate droplets of soft matter, in particular, lyotropic mesophases formed from selfassembly of different surfactants and lipids, which can be analyzed in a contact-less manner by X-ray scattering in a controlled gas-phase environment. On the macroscopic length scale, the dimensions and the orientation of the particle are shaped by the ultrasonic field, while on the microscopic length scale the nanostructure can be controlled by varying the humidity of the atmosphere around the droplet. We demonstrate levitation and in situ phase transitions of micellar, hexagonal, bicontinuous cubic, and lamellar phases. The technique opens up a wide range of new experimental approaches of fundamental importance for environmental, biological, and chemical research.