Introduction Glutaminase inhibitors target cancer cells by blocking the conversion of glutamine to glutamate, thereby potentially interfering with anaplerosis and synthesis of amino acids and glutathione. The drug CB-839 has shown promising effects in preclinical experiments and is currently undergoing clinical trials in several human malignancies, including triple-negative breast cancer (TNBC). However, response to glutaminase inhibitors is variable and there is a need for identification of predictive response biomarkers. The aim of this study was to determine how glutamine is utilized in two patient-derived xenograft (PDX) models of breast cancer representing luminal-like/ER+ (MAS98.06) and basal-like/triple-negative (MAS98.12) breast cancer and to explore the metabolic effects of CB-839 treatment. Experimental MAS98.06 and MAS98.12 PDX mice received CB-839 (200 mg/kg) or drug vehicle two times daily p.o. for up to 28 days ( n = 5 per group), and the effect on tumor growth was evaluated. Expression of 60 genes and seven glutaminolysis key enzymes were determined using gene expression microarray analysis and immunohistochemistry (IHC), respectively, in untreated tumors. Uptake and conversion of glutamine were determined in the PDX models using HR MAS MRS after i.v. infusion of [5- 13 C] glutamine when the models had received CB-839 (200 mg/kg) or vehicle for 2 days ( n = 5 per group). Results Tumor growth measurements showed that CB-839 significantly inhibited tumor growth in MAS98.06 tumors, but not in MAS98.12 tumors. Gene expression and IHC analysis indicated a higher proline synthesis from glutamine in untreated MAS98.06 tumors. This was confirmed by HR MAS MRS of untreated tumors demonstrating that MAS98.06 used glutamine to produce proline, glutamate, and alanine, and MAS98.12 to produce glutamate and lactate. In both models, treatment with CB-839 resulted in accumulation of glutamine. In addition, CB-839 caused depletion of alanine, proline, and glutamate ([1-13C] glutamate) in the MAS98.06 model. Conclusion Our findings indicate that TNBCs may not be universally sensitive to glutaminase inhibitors. The major difference in the metabolic fate of glutamine between responding MAS98.06 xenografts and non-responding MAS98.12 xenografts is the utilization of glutamine for production of proline. We therefore suggest that addiction to proline synthesis from glutamine is associated with response to CB-839 in breast cancer. Graphical abstract The effect of glutaminase inhibition in two breast cancer patient-derived xenograft (PDX) models. 13 C HR MAS MRS analysis of tumor tissue from CB-839-treated and untreated models receiving 13 C-labeled glutamine ([5- 13 C] Gln) shows that the glutaminase inhibitor CB-839 is causing an a...

It has been suggested that community, social cohesion and territorial ties in neighbourhoods may be characterised by three directions: the lost, the saved and the transformed. On the basis of a number of case studies in a Norwegian city, it is found that these three trends exist together, on the basis of various local interactive practices. The concept of an interaction pretext is developed to answer in a more nuanced way how various forms of social ties are developed, maintained and/or altered. By combining this concept with local activity, four community types are specified that may characterise different neighbourhoods and that may also exist in parallel at one place: the passing-by community, the tight community, the weak community, and the split community. Demonstrating the potential of a more detailed empirical approach to the community question, the paper warns against too analytically shallow suggestions about their development. By understanding how neighbourhoods develop socially in different ways, it may be possible to increase the probability of better community planning.

Situational domestication and the origin of the café worker speciesabstract Given the pervasiveness of free Wi-Fi zones in cafés, use of laptops, tablets and smart phones supports the transformation of cafés from social spaces to work spaces for many customers. In this article we analyse, on the basis of an ethnographic study of individuals' laptop work in urban cafés in Norway and the UK, (1) what it is about cafés that makes people visit them for working purposes, and (2) how individual laptop work changes the social life of such venues. By linking our analysis to theories of communal processes and the domestication of technologies, we put forward the concept of 'situational domestication', encompassing the aspects of socially embedded individual working. Consequently, the close study of how café spaces are being used for work offers insights into how progressively technologised work and work habits influence not only work itself, but also public space at a broader level.

This collective editorial on the neoliberal university follows eight days of strike action at sixty UK universities called by the University and College Union (UCU) in two separate legal disputes, one on pensions and one on pay and working conditions. Anticipating the recent labor strike after previous industrial disputes in 2018 at UK universities, the work included here emanates from two dialogues at the Nordic Geographers Meeting (NGM) in summer 2019, a public meeting called Protest Pub and a conference session on the neoliberal subject and the neoliberal academy. After an opening statement by the editors, this collective endeavor begins with the urgent collaborative action of graduate students and early-career academics and is followed by reflections on life in the neoliberal academy from those involved in the dialogues at the NGM 2019 in Trondheim. Additionally, the editorial introduces the content of the present issue.

Electricity demand-side management (DSM) programs are becoming increasingly important to energy system managers in advanced industrialized countries, especially those with high renewable energy penetration. As energy user participation is paramount for their success but has proven to be difficult to obtain, we explore the usefulness of the 'social license' concept, originally developed in the mining sector, to refer to the process of creating acceptance in DSM programs aimed at managing or controlling household energy resources such EVs, batteries, and heating and cooling devices. We argue that analyzing the attainment or lack of 'social license' may be useful to energy policy-makers and researchers for understanding public concerns with not only supply-side energy resources, but also DSM. We do so by (1) drawing attention to potential frictions between demands for flexibility on the one hand and social practices and habits on the other; (2) attending to the ways that users'