Histone deacetylase 3 unconventional splicing mediates endothelial-to- mesenchymal transition through transforming growth factor β2

Histone deacetylase 3 (HDAC3) plays a critical role in the maintenance of endothelial integrity and other physiological processes. In this study, we demonstrated that HDAC3 undergoes unconventional splicing during stem cell differentiation. Four different splicing variants have been identified, designated as HD3α, -β, -γ, and -Δ, respectively. HD3α was confirmed in stem cell differentiation by specific antibody against the sequences from intron 12. Immunofluorescence staining indicated that the HD3α isoform co-localized with CD31-positive or α-smooth muscle actin-positive cells at different developmental stages of mouse embryos. Overexpression of HD3α reprogrammed human aortic endothelial cells into mesenchymal cells featuring an endothelial-to-mesenchymal transition (EndMT) phenotype. HD3α directly interacts with HDAC3 and Akt1 and selectively activates transforming growth factor β2 (TGFβ2) secretion and cleavage. TGFβ2 functioned as an autocrine and/or paracrine EndMT factor. The HD3α-induced EndMT was both PI3K/Akt- and TGFβ2-dependent. This study provides the first evidence of the role of HDAC3 splicing in the maintenance of endothelial integrity.

Automated detection and measurement of isolated retinal arterioles by a combination of edge enhancement and cost analysis

Pressure myography studies have played a crucial role in our understanding of vascular physiology and pathophysiology. Such studies depend upon the reliable measurement of changes in the diameter of isolated vessel segments over time. Although several software packages are available to carry out such measurements on small arteries and veins, no such software exists to study smaller vessels (<50 µm in diameter). We provide here a new, freely available open-source algorithm, MyoTracker, to measure and track changes in the diameter of small isolated retinal arterioles. The program has been developed as an ImageJ plug-in and uses a combination of cost analysis and edge enhancement to detect the vessel walls. In tests performed on a dataset of 102 images, automatic measurements were found to be comparable to those of manual ones. The program was also able to track both fast and slow constrictions and dilations during intraluminal pressure changes and following application of several drugs. Variability in automated measurements during analysis of videos and processing times were also investigated and are reported. MyoTracker is a new software to assist during pressure myography experiments on small isolated retinal arterioles. It provides fast and accurate measurements with low levels of noise and works with both individual images and videos. Although the program was developed to work with small arterioles, it is also capable of tracking the walls of other types of microvessels, including venules and capillaries. It also works well with larger arteries, and therefore may provide an alternative to other packages developed for larger vessels when its features are considered advantageous.

Neolithic settlement at the woodland’s edge: palynological data and timber architecture in Orkney, Scotland

It has often been assumed that the islands of Orkney were essentially treeless throughout much of the Holocene, with any ‘scrub’ woodland having been destroyed by Neolithic farming communities by around 3500 cal. BC. This apparently open, hyper-oceanic environment would presumably have provided quite marginal conditions for human settlement, yet Neolithic communities flourished and the islands contain some of the most spectacular remains of this period in north-west Europe. The study of new Orcadian pollen sequences, in conjunction with the synthesis of existing data, indicates that the timing of woodland decline was not synchronous across the archipelago, beginning in the Mesolithic, and that in some areas woodland persisted into the Bronze Age. There is also evidence to suggest that woodland communities in Orkney were more diverse, and therefore that a wider range of resources was available to Neolithic people, than has previously been assumed. Recent archaeological investigations have revealed evidence for timber buildings at early Neolithic settlement sites, suggesting that the predominance of stone architecture in Neolithic Orkney may not have been due to a lack of timber as has been supposed. Rather than simply reflecting adaptation to resource constraints, the reasons behind the shift from timber to stone construction are more complex and encompass social, cultural and environmental factors.

On Being Let Loose in the Field: The Execution of Professional Ethics

In recent years concerns over litigation and the trend towards close monitoring of academic activity has seen the effective hijacking of research ethics by university managers and bureaucrats. This can effectively curtail cutting edge research as perceived ‘safe’ research strategies are encouraged. However, ethics is about more than research governance. Ultimately, it seeks to avoid harm and to increase benefits to society. Rural development debate is fairly quiet on the question of ethics, leaving guidance to professional bodies. This study draws on empirical research that examined the lives of migrant communities in Northern Ireland. This context of increasingly diverse rural development actors provides a backdrop for the way in which the researcher navigates through ethical issues as they unfold in the field. The analysis seeks to relocate ethics from being an annoying bureaucratic requirement to one where it is inherent to rigorous and professional research and practice. It reveals how attention to professional ethics can contribute to effective, situated and reflexive practice, thus transforming ethics to become an asset to professional researchers.

The interaction of surface plasmon polaritons with a silver film edge

A prism coupling arrangement is used to excite surface plasmons at the surface of a thin silver aim and a photon scanning tunnelling microscope is used to detect the evanescent field above the silver surface. Excitation of the silver/ air mode of interest is performed at lambda(1) = 632 . 8 nm using a tightly focused beam, while the control of the tip is effected by exciting a counter-propagating surface plasmon field at a different wavelength. lambda(2) = 543 . 5 nm, using an unfocused beam covering a macroscopic area. Propagation of the red surface plasmon is evidenced by an exponential tail extending away from the launch site, but this feature is abruptly truncated if the surface plasmon encounters the edge of the silver film - there is no specularly reflected 'beam'. Importantly, the radiative decay of the surface mode at the film edge is observable only at larger tip-sample separations, emphasizing the importance of accessing the mesoscopic regime.

Progress at JET in integrating ITER-relevant core and edge plasmas within the constraints of an ITER-like wall

This paper reports the progress made at JET-ILW on integrating the requirements of the reference ITER baseline scenario with normalized confinement factor of 1, at a normalized pressure of 1.8 together with partially detached divertor whilst maintaining these conditions over many energy confinement times. The 2.5 MA high triangularity ELMy H-modes are studied with two different divertor configurations with D-gas injection and nitrogen seeding. The power load reduction with N seeding is reported. The relationship between an increase in energy confinement and pedestal pressure with triangularity is investigated. The operational space of both plasma configurations is studied together with the ELM energy losses and stability of the pedestal of unseeded and seeded plasmas. The achievement of stationary plasma conditions over many energy confinement times is also reported.

Transforming Post-Catholic Ireland: Religious Practice in Late Modernity

Transforming Post-Catholic Ireland is the first major book to explore the dynamic religious landscape of contemporary Ireland, north and south, and to analyse the island’s religious transition. It confirms that the Catholic Church’s long-standing ‘monopoly’ has well and truly disintegrated, replaced by a mixed, post-Catholic religious ‘market’ featuring new and growing expressions of Protestantism, as well as other religions. It describes how people of faith are developing ‘extra-institutional’ expressions of religion, keeping their faith alive outside or in addition to the institutional Catholic Church.

Drawing on island-wide surveys of clergy and laypeople, as well as more than 100 interviews, this book describes how people of faith are engaging with key issues such as increased diversity, reconciliation to overcome the island’s sectarian past, and ecumenism. It argues that extra-institutional religion is especially well-suited to address these and other issues due to its freedom and flexibility when compared to traditional religious institutions. It describes how those who practice extra-institutional religion have experienced personal transformation, and analyses the extent that they have contributed to wider religious, social, and political change. On an island where religion has caused much pain, from clerical sexual abuse scandals, to sectarian violence, to a frosty reception for some immigrants, those who practice their faith outside traditional religious institutions may hold the key to transforming post-Catholic Ireland into a more reconciled society.

A numerical study of trailing edge geometry for low inertia automotive mixed flow turbines

Abstract. Mixed flow turbines can offer improvements over typical radial turbines used in automotive turbochargers, with respect to transient performance and low velocity ratio efficiency. Turbine rotor mass dominates the rotating inertia of the turbocharger’s rotating assembly, and any reductions of mass in the outer radii of the wheel, including the rotor back-disk, can significantly reduce this inertia and improve the acceleration of the assembly. Off-design, low velocity ratio conditions are typified by highly tangential flow at the rotor inlet and a non-zero inlet blade angle is desirable for such operating conditions. This is achievable in a Mixed Flow Turbine without increasing bending stresses within the rotor blade, which is beneficial in high speed and high inlet temperature turbine designs.
This study considers the meridional geometry of Mixed Flow Turbines using a multi-disciplinary study to assess both the structural and aerodynamic performance of each rotor, incorporating both CFD and FEA. Variations of rotor trailing edge were investigated at different operating conditions representing both on- and off-design operation within the constraints of existing hardware geometries. In all cases, the performance is benchmarked against an existing state-of-the-art radial turbocharger turbine with consideration of rotor inertia and its benefit for engine transient performance. The results indicate the influence of these parameters and this report details their benefits with respect to turbocharging a downsized, automotive engine.

Small molecular logic systems can draw the outlines of objects via edge visualization

The recently-discovered ability of small logical molecules to recognize edges is exploited to achieve outline drawing from binary templates. Outlines of arbitrary curvature, several colours and thicknesses down to 1 mm are drawn in around 30 min or less by employing a common laboratory two-colour ultraviolet lamp. The outlines and the light dose-driven XOR logic with fluorescence output or ‘off-on-off’ action which is observed in the irradiated regions are modelled by combining foundational principles of photochemistry, acid-base neutralization and diffusion.

The effect of ionization on the populations of excited levels of C IV and C V in tokamak edge plasmas

The main populating and depopulating mechanisms of the excited energy levels of ions in plasmas with densities <10²³-10²⁴ m^-3 are electron collisional excitation from the ion's ground state and radiative decay, respectively, with the majority of the electron population being in the ground state of the ionization stage. Electron collisional ionization is predominately expected to take place from one ground state to that of the next higher ionization stage. However, the question arises as to whether, in some cases, ionization can also affect the excited level populations. This would apply particularly to those cases involving transient events such as impurity influxes in a laboratory plasma. An analysis of the importance of ionization in populating the excited levels of ions in plasmas typical of those found in the edge of tokamaks is undertaken for the C IV and C V ionization stages. The emphasis is on those energy levels giving rise to transitions of most use for diagnostic purposes (n ≤ 5). Carbon is chosen since it is an important contaminant of JET plasmas; it was the dominant low Z impurity before the installation of the ITER-like wall and is still present in the plasma after its installation. Direct electron collisional ionization both from and to excited levels is considered. Distorted-wave flexible atomic code calculations are performed to generate the required ionization cross sections, due to a lack of atomic data in the literature. Employing these data, ionization from excited level populations is not found to be significant in comparison with radiative decay. However, for some energy levels, ionization terminating in the excited level has an effect in the steady-state of the order of the measurement errors (±10%). During transient events, ionization to excited levels will be of more importance and must be taken into account in the calculation of excited level populations. More accurate atomic data, including possible resonance contributions to the cross sections, would tend to increase further the importance of these effects. 

Practicing peace: Psychological roots of transforming conflicts

The practice of sustainable peace is a process that must be initiated, nourished and revised. The
“social energies” of conflict transformation – truth, mercy, justice, peace – offer a useful model to describe the transformative power of this practice. These social energies can be conceptualized as a combination of norms or values, on the one hand, and actions directed toward social reconstruction, on the other. As such, the social energies of conflict transformation are both the guideposts and the engine in the journey of practicing sustainable peace. This article begins by
linking psychological constructs of narrative/voice, empathy/altruism, individual/collective guilt, and security/fear with the social energies, highlighting the interdependence of processes and shifting the focus away from pathology toward an emphasis on harmony. An empirical application of how the four social energies contribute to the mobilization, maintenance and adaptations in on-going peace processes in post-war Guatemala is then presented. By analyzing the interaction among diverse actors and goals in the decade and a half since the signing of the 1996 Peace Accords, current theory is extended in two ways: a) differentiation between elite and grassroots initiatives, and b) specification and evaluation the impact of various efforts on episodic and structural violence. We conclude that although national and local processes have
had limited success, more integrated practices of truth, mercy, justice and peace are necessary if Guatemala is to make sustainable peace a reality. The findings from this case study have policy and practical implications for other countries facing protracted, violent conflict.

Transforming Growth Factor-beta superfamily:evaluation as breast cancer biomarkers and preventive agents

The Transforming Growth Factor-beta (TGFbeta) superfamily of cytokines is comprised of a number of structurally-related, secreted polypeptides that regulate a multitude of cellular processes including proliferation, differentiation and neoplastic transformation. These growth regulatory molecules induce ligand-mediated hetero-oligomerization of distinct type II and type I serine/threonine kinase receptors that transmit signals predominantly through receptor-activated Smad proteins but also induce Smad-independent pathways. Ligands, receptors and intracellular mediators of signaling initiated by members of the TGFbeta family are expressed in the mammary gland and disruption of these pathways may contribute to the development and progression of human breast cancer. Since many facets of TGFbeta and breast cancer have been recently reviewed in several articles, except for discussion of recent developments on some aspects of TGFbeta, the major focus of this review will be on the role of activins, inhibins, BMPs, nodal and MIS-signaling in breast cancer with emphasis on their utility as potential diagnostic, prognostic and therapeutic targets.

The View from the Edge: The Proyecto Arqueológico Chihuahua (PAC) 1990 to 2010: An Overview

The work of the Proyecto Arqueológico Chihuahua (PAC) has played an integral role in defining the origins and characteristics of the Chihuahua culture area, also known as the Casas Grandes Regional System. PAC has developed a critical suite of radiocarbon dates for the southern zone, undertaken the first substantial investigations of the Viejo period (ca. A.D. 800textendash1200 or 1250) since the early 1960s, and added to knowledge of the southern Medio period (ca. A.D. 1250textendash1450). The project has also elucidated the chronology, settlement patterns, subsistence strategies, and technology for both periods. Results of our research indicate continuity between the Viejo period, characterized by small pithouse settlements, and the pueblo focused Medio period in the southern zone, with some poorly understood external influences from both western Mesoamerica to the south and the American Southwest to the north shaping events within the area.