Spatial competition constrains resistance to targeted cancer therapy

Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden and resistance in tumour spheroids, but not in monolayer culture. Mathematical modelling indicates that tumour spatial structure amplifies the fitness penalty of resistant cells, and identifies their relative fitness as a critical determinant of the clinical benefit of AT. Our results justify further investigation of AT with kinase inhibitors

Encountering Berlant part one: Concepts otherwise

In Part 1 of ‘Encountering Berlant’, we encounter the promise and provocation of Lauren Berlant's work. In 1000-word contributions, geographers and others stay with what Berlant's thought offers contemporary human geography. They amplify an encounter with their work, demonstrating how a concept, idea, or style disrupts something, opens up a new possibility, or simply invites thinking otherwise. The encounters range across the incredible body of work Berlant left us with, from the ‘national sentimentality’ trilogy through to recent work on negativity. Varying in form and tone, the encounters exemplify and enact the inexhaustible plenitude of Berlant's thought: fantasy, the case, love, impasse, feel tanks, slow death, ellipses, gesture, attrition, intimate public, ambivalence, style. Part 2 of ‘Encountering Berlant’ focuses on Berlant's most influential concept: ‘cruel optimism’. Across these heterogeneous encounters, Berlant's enduring concern with the tensions and possibilities of relationality and how to enact better forms of common life shine through. These enduring concerns and Berlant's commitment to the incoherence and overdetermination of phenomena are summarised in the Introduction, which also explores how Berlant's work has been engaged with in geography. The result is a repository of what an encounter with Berlant's thought makes possible. Short Abstract Part 1 of ‘Encountering Berlant’ explores the promise and provocation of Lauren Berlant's work. Contributors amplify an encounter with Berlant's concepts, tones, and styles, drawing out their implications for understanding relationality and how to invent and live better ways of being in common. The result is a repository of what Berlant's thinking offers geographers

Encountering Berlant part 1: Concepts otherwise

In Part 1 of ‘Encountering Berlant’, we encounter the promise and provocation of Lauren Berlant's work. In 1000-word contributions, geographers and others stay with what Berlant's thought offers contemporary human geography. They amplify an encounter with their work, demonstrating how a concept, idea, or style disrupts something, opens up a new possibility, or simply invites thinking otherwise. The encounters range across the incredible body of work Berlant left us with, from the ‘national sentimentality’ trilogy through to recent work on negativity. Varying in form and tone, the encounters exemplify and enact the inexhaustible plenitude of Berlant's thought: fantasy, the case, love, impasse, feel tanks, slow death, ellipses, gesture, attrition, intimate public, ambivalence, style. Part 2 of ‘Encountering Berlant’ focuses on Berlant's most influential concept: ‘cruel optimism’. Across these heterogeneous encounters, Berlant's enduring concern with the tensions and possibilities of relationality and how to enact better forms of common life shine through. These enduring concerns and Berlant's commitment to the incoherence and overdetermination of phenomena are summarised in the Introduction, which also explores how Berlant's work has been engaged with in geography. The result is a repository of what an encounter with Berlant's thought makes possible

Encountering Berlant part 1: Concepts otherwise

In Part 1 of ‘Encountering Berlant’, we encounter the promise and provocation of Lauren Berlant's work. In 1000-word contributions, geographers and others stay with what Berlant's thought offers contemporary human geography. They amplify an encounter with their work, demonstrating how a concept, idea, or style disrupts something, opens up a new possibility, or simply invites thinking otherwise. The encounters range across the incredible body of work Berlant left us with, from the ‘national sentimentality’ trilogy through to recent work on negativity. Varying in form and tone, the encounters exemplify and enact the inexhaustible plenitude of Berlant's thought: fantasy, the case, love, impasse, feel tanks, slow death, ellipses, gesture, attrition, intimate public, ambivalence, style. Part 2 of ‘Encountering Berlant’ focuses on Berlant's most influential concept: ‘cruel optimism’. Across these heterogeneous encounters, Berlant's enduring concern with the tensions and possibilities of relationality and how to enact better forms of common life shine through. These enduring concerns and Berlant's commitment to the incoherence and overdetermination of phenomena are summarised in the Introduction, which also explores how Berlant's work has been engaged with in geography. The result is a repository of what an encounter with Berlant's thought makes possible

DNA damage restrains CDK2 activity to delay S-M progression and promote cell cycle exit

International audienc

Partial Horizontal Differentiation in Croatian Higher Education: How Ideas, Institutions and Interests Shape the Policy Process

This chapter looks into the historical process of establishing and strengthening of the non-university sector in Croatia since the mid-1990s onwards and offers an account of its outcome. Initially, the process was part of the country’s broader efforts not only to ensure regionally balanced development, but also to improve quality, efficiency and accessibility to higher education. Since 2001, it was further embedded in broader higher education reform efforts, especially the implementation of the Bologna Process. This reform entailed, on the one hand, the establishment of non-university – professionally oriented – higher education institutions and, on the other hand, a gradual abolishment of professional study programmes in universities. The authors suggest that only a small part of the reform goals have been achieved, whereby some non-university institutions have been established and the number of students enrolled in professional programmes at universities has somewhat decreased. Effectively, the reform failed to align the distinction between types of higher education institutions and types of programmes, rendering the binary divide, at best, blurred. The authors argue that such outcome has been a result of, on the one hand, the governments’ reliance on formal regulation as the main policy instrument, which allowed for discretion in interpretation and enforcement of rules, and, on the other hand, the fact that the most dominant actor – universities – has continuously opposed the reforms