Crystal Structures of Tcl1 Family Oncoproteins and Their Conserved Surface Features

Members of the TCL1 family of oncogenes are abnormally expressed in mature T-cell leukemias and B-cell lymphomas. The proteins are involved in the coactivation of protein kinase B (Akt/PKB), a key intracellular kinase. The sequences and crystal structures of three Tcl1 proteins were analyzed in order to understand their interactions with Akt/PKB and the implications for lymphocyte malignancies. Tcl1 proteins are ~15 kD and share 25—80% amino acid sequence identity. The tertiary structures of mouse Tcl1, human Tcl1, and Mtcp1 are very similar. Analysis of the structures revealed conserved semi-planar surfaces that have characteristics of surfaces involved in protein-protein interactions. The Tcl1 proteins show differences in surface charge distribution and oligomeric state suggesting that they do not interact in the same way with Akt/PKB and other cellular protein(s)

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

A major risk factor for ovarian cancer is germline mutations of BRCA1/2. It has been found that (80%) of cellular models with acquired platinum or taxane resistance display an inverse resistance relationship, that is collateral sensitivity to the other agent. We used a clinically relevant comparative selection strategy to develop novel chemoresistant cell lines which aim to investigate the mechanisms of resistance that arise from different exposures of carboplatin and taxol on cells having BRCA1 function (UPN251) or dysfunction (OVCAR8). Resistance to carboplatin and taxol developed quicker and more stably in UPN251 (BRCA1-wildtype) compared to OVCAR8 (BRCA1-methylated). Alternating carboplatin and taxol treatment delayed but did not prevent resistance development when compared to single-agent administration. Interestingly, the sequence of drug exposure influenced the resistance mechanism produced. UPN251-6CALT (carboplatin first) and UPN251-6TALT (taxol first) have different profiles of cross resistance. UPN251-6CALT displays significant resistance to CuSO4 (2.3-fold, p=0.004) while UPN251-6TALT shows significant sensitivity to oxaliplatin (0.6-fold, p=0.01). P-glycoprotein is the main mechanism of taxol resistance found in the UPN251 taxane-resistant sublines. UPN251 cells increase cellular glutathione levels (3.0-fold, p=0.02) in response to carboplatin treatment. However, increased glutathione is not maintained in the carboplatin-resistant sublines. UPN251-7C and UPN251-6CALT are low-level resistant to CuSO4 suggesting alterations in copper metabolism. However, none of the UPN251 sublines have alterations in the protein expression of ATP7A or CTR1. The protein expression of BRCA1 and MRP2 is unchanged in the UPN251 sublines. The UPN251 sublines remain sensitive to parp inhibitors veliparib and CEP8983 suggesting that these agents are candidates for the treatment of platinum/taxane resistant ovarian cancer patients

Detection of Stance-Related Characteristics in Social Media Text

In this paper, we present a study for the identification of stance-related features in text data from social media. Based on our previous work on stance and our findings on stance patterns, we detected stance-related characteristics in a data set from Twitter and Facebook. We extracted various corpus-, quantitative- and computational-based features that proved to be significant for six stance categories (contrariety, hypotheticality, necessity, prediction, source of knowledge, and uncertainty), and we tested them in our data set. The results of a preliminary clustering method are presented and discussed as a starting point for future contributions in the field. The results of our experiments showed a strong correlation between different characteristics and stance constructions, which can lead us to a methodology for automatic stance annotation of these data

The wages of whiteness in the absence of wages: racial capitalism, reactionary intercommunalism and the rise of Trumpism

In November 1970, Black Panther Party leader Huey P. Newton gave a lecture at Boston College where he introduced his theory of intercommunalism. Newton re-articulated Marxist theories of imperialism through the lens of the Black liberation struggle and argued that imperialism had entered a new phase called ‘reactionary intercommunalism’. Newton’s theory of intercommunalism o ers nothing less than a proto-theorisation of what we have come to call neo-liberal globalisation and its e ects on what W. E. B. Du Bois had seen as the racialisation of modern imperialism. Due to the initial historical dismissal of the Black Panther Party’s political legacy, Newton’s thought has largely been neglected for the past 40 years. This paper revisits Newton’s theory of intercommunalism, with the aim of achieving some form of epistemic justice for his thought, but also to highlight how Newton’s recasting of imperialism as reactionary intercommunalism provides critical insight into the rise of Trumpism in the US

Delamination properties of laminated glass windows subject to blast loading

Delamination processes absorb significant amounts of energy in laminated glass windows when they are subjected to blast loads. Blast tests were performed previously and their results had been used to calculate the loads imposed on the support systems. In this research, the delamination process at realistic deformation rates was studied to understand the reaction force response obtained. Laboratory tensile tests were performed on pre-cracked laminated glass specimens to investigate their delamination behaviour. The experiments confirmed the presence of a plateau in the force-deflection graphs, suggesting that the delamination process absorbed significant energy. The experimental results were then employed to calibrate FEA models of the delamination process with the aim of estimating the delamination energy of the polyvinyl butyral (PVB) membrane and glass layers and its relationship with deformation speed. The delamination energies obtained through this research, if used with the appropriate PVB material model, are a valuable new tool new tool in the modelling and design of laminated glass façade structures

Identity, race and faith: The role of faith in post-Apartheid South Africa

South Africa has experienced an unprecedented influx of migrants in the 21st century. Immigration and race have contributed to the raising of important questions of identity and social inclusion. Immigration and race are two crucial phenomena for the church in South Africa because the overwhelming majority of immigrants to South Africa are affiliated to Christianity and active participants in worshipping communities. This article is an attempt to critically engage with the complex phenomena of immigration and race for the role of Christianity in identity. I will attempt to show how mainstream Christianity as an open-ended narrative and can provide the space for creative tension between the ‘host’ and ‘stranger’ for identity formation. I will use the theoretical framework of Don Browning’s correlational approach to demonstrate how the experience of immigrants and minority race groups creates identity of self and the constructive other.DHE

Idiopathic interstitial pneumonia: Do community and academic physicians agree on diagnosis?

Rationale: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results: Each observer’s diagnosis was coded into one of eight categories. A statistic allowing formultiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (Kappa= 0.55–0.71) than within community centers (Kappa=0.32–0.44). Clinically significant disagreement was present between academic and communitybased physicians (Kappa=0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91941/1/2007 AJRCCM Idiopathic interstitial pneumonia - Do community and academic physicians agree on diagnosis.pd

The discourse dynamics approach to metaphor and metaphor-led discourse analysis

The use of metaphor as a tool to uncover people's ideas, attitudes, and values through analysis of discourse is demonstrated and illustrated with data collected in a social science research project. A 'discourse dynamics' approach to metaphor situated within a complexity/dynamic systems perspective is developed. This approach is turned into a method of 'metaphor-led discourse analysis' which is described in detail, using a focus group discussion to illustrate the procedure: transcription, metaphor identification, coding metaphors and using software, and finding patterns of metaphor use from coded data. The reasoning that justifies decisions at each stage of the procedure is made explicit so that the trustworthiness of the method can be maximized. The method of metaphor-led discourse analysis has been developed through a series of empirical projects to be accessible and relevant to social science researchers as well as to metaphor scholars

Colonialism, postcolonialism and the liberal welfare state

This article addresses the colonial and racial origins of the welfare state with a particular emphasis on the liberal welfare state of the USA and UK. Both are understood in terms of the centrality of the commodified status of labour power expressing a logic of market relations. In contrast, we argue that with a proper understanding of the relations of capitalism and colonialism, the sale of labour power as a commodity already represents a movement away from the commodified form of labour represented by enslavement. European colonialism is integral to the development of welfare states and their forms of inclusion and exclusion which remain racialised through into the twenty-first century