Cultures of transformation: An integrated framework for transformative action

The challenges posed by climate change have generated many initiatives that seek to implement societal transformations. In most cases, these focus on technology developments, adoption and diffusion but neglect the social and cultural dimensions of a transformation. Insights from systems and behavioural sciences can provide valuable guidance on these aspects, but the utility of this literature is limited by two factors. Firstly, the literature on the intersection between social transformation and psychological processes of behaviour change by individuals is limited. Secondly, the complex technical nature of much of the transition relevant literature limits its accessibility by stakeholders outside academia. We seek to address these challenges through the development of a transdisciplinary Transformation Process Framework for use as a ‘knowledge integration’ tool as part of a co-design process for transformative change. The Framework: (1) develops a systematic narrative of the transformational changes that need to be triggered at multiple scales (from individual to society), (2) generates a map to identify key variables, drivers, and blockers in a transformation process integrating different knowledge from fragmented disciplines; (3) serves as a tool to support the exploration of relevant academic (and other) literature to collate and utilise relevant knowledge. © 2022Suggestion H.P., A.H.S. and A.A.K was supported by the H2020 European Commission Project ‘PARIS REINFORCE’ under grant agreement no. 820846 . This work also originated in, and benefited from, discussions with multiple research and non-governmental organisations. We acknowledge and thank all involved in helping us develop and refine our ideas. We also thank two anonymous referees who provided valuable and insights comments that significantly helped in improving the original manuscript. We also grateful for the constructive and thoughtful comments provided by two anonymous referees

Mild Traumatic Brain Injury and Treatment Response in Prolonged Exposure for PTSD

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98185/1/jts21813.pd

SibylFS: Formal specification and oracle-based testing for POSIX and real-world file systems

Systems depend critically on the behaviour of file systems, but that behaviour differs in many details, both between implementations and between each implementation and the POSIX (and other) prose specifications. Building robust and portable software requires understanding these details and differences, but there is currently no good way to systematically describe, investigate, or test file system behaviour across this complex multi-platform interface. In this paper we show how to characterise the envelope of allowed behaviour of file systems in a form that enables practical and highly discriminating testing. We give a mathematically rigorous model of file system behaviour, SibylFS, that specifies the range of allowed behaviours of a file system for any sequence of the system calls within our scope, and that can be used as a test oracle to decide whether an observed trace is allowed by the model, both for validating the model and for testing file systems against it. SibylFS is modular enough to not only describe POSIX, but also specific Linux, OS X and FreeBSD behaviours. We complement the model with an extensive test suite of over 21 000 tests; this can be run on a target file system and checked in less than 5 minutes, making it usable in practice. Finally, we report experimental results for around 40 configurations of many file systems, identifying many differences and some serious flaws

Biological And Symptom Changes In Posttraumatic Stress Disorder Treatment: A Randomized Clinical Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110764/1/da22331.pd

Exploiting the Temporal Logic Hierarchy and the Non-Confluence Property for Efficient LTL Synthesis

The classic approaches to synthesize a reactive system from a linear temporal logic (LTL) specification first translate the given LTL formula to an equivalent omega-automaton and then compute a winning strategy for the corresponding omega-regular game. To this end, the obtained omega-automata have to be (pseudo)-determinized where typically a variant of Safra's determinization procedure is used. In this paper, we show that this determinization step can be significantly improved for tool implementations by replacing Safra's determinization by simpler determinization procedures. In particular, we exploit (1) the temporal logic hierarchy that corresponds to the well-known automata hierarchy consisting of safety, liveness, Buechi, and co-Buechi automata as well as their boolean closures, (2) the non-confluence property of omega-automata that result from certain translations of LTL formulas, and (3) symbolic implementations of determinization procedures for the Rabin-Scott and the Miyano-Hayashi breakpoint construction. In particular, we present convincing experimental results that demonstrate the practical applicability of our new synthesis procedure

Aptamers that recognize drug-resistant HIV-1 reverse transcriptase

Drug-resistant variants of HIV-1 reverse transcriptase (RT) are also known to be resistant to anti-RT RNA aptamers. In order to be able to develop diagnostics and therapies that can focus on otherwise drug-resistant viruses, we have isolated two aptamers against a well-known, drug-resistant HIV-1 RT, Mutant 3 (M3) from the multidrug-resistant HIV-1 RT panel. One aptamer, M302, bound M3 but showed no significant affinity for wild-type (WT) HIV-1 RT, while another aptamer, 12.01, bound to both M3 and WT HIV-1 RTs. In contrast to all previously selected anti-RT aptamers, neither of these aptamers showed observable inhibition of either polymerase or RNase H activities. Aptamers M302 and 12.01 competed with one another for binding to M3, but they did not compete with a pseudoknot aptamer for binding to the template/primer cleft of WT HIV-1 RT. These results represent the surprising identification of an additional RNA-binding epitope on the surface of HIV-1 RT. M3 and WT HIV-1 RTs could be distinguished using an aptamer-based microarray. By probing protein conformation as a correlate to drug resistance we introduce an additional and useful measure for determining HIV-1 drug resistance

State of the art and latest advances in exploring business models for nature-based solutions

Nature-based solutions (NBS) offer multiple solutions to urban challenges simultaneously, but realising funding for NBS remains a challenge. When the concept of NBS for societal challenges was first defined by the EC in 2017, financing was recognised as one of the major challenges to its mainstreaming. The complexity of NBS finance has its origin in the multiple benefits/stakeholders involved, which obscures the argument for both public and private sector investment. Since 2017, subsequent waves of EU research-and innovation-funded projects have substantially contributed to the knowledge base of funding and business models for NBS, particularly in the urban context. Collaborating and sharing knowledge through an EU Task Force, this first set of EU projects laid important knowledge foundations, reviewing existing literature, and compiling empirical evidence of different financing approaches and the business models that underpinned them. The second set of EU innovation actions advanced this knowledge base, developing and testing new implementation models, business model tools, and approaches. This paper presents the findings of these projects from a business model perspective to improve our understanding of the value propositions of NBS to support their mainstreaming

A calibrated diversity assay for nucleic acid libraries using DiStRO—a Diversity Standard of Random Oligonucleotides

We have determined diversities exceeding 1012 different sequences in an annealing and melting assay using synthetic randomized oligonucleotides as a standard. For such high diversities, the annealing kinetics differ from those observed for low diversities, favouring the remelting curve after annealing as the best indicator of complexity. Direct comparisons of nucleic acid pools obtained from an aptamer selection demonstrate that even highly complex populations can be evaluated by using DiStRO, without the need of complicated calculations

A modified bacterial one-hybrid system yields improved quantitative models of transcription factor specificity

We examine the use of high-throughput sequencing on binding sites recovered using a bacterial one-hybrid (B1H) system and find that improved models of transcription factor (TF) binding specificity can be obtained compared to standard methods of sequencing a small subset of the selected clones. We can obtain even more accurate binding models using a modified version of B1H selection method with constrained variation (CV-B1H). However, achieving these improved models using CV-B1H data required the development of a new method of analysis—GRaMS (Growth Rate Modeling of Specificity)—that estimates bacterial growth rates as a function of the quality of the recognition sequence. We benchmark these different methods of motif discovery using Zif268, a well-characterized C2H2 zinc-finger TF on both a 28 bp randomized library for the standard B1H method and on 6 bp randomized library for the CV-B1H method for which 45 different experimental conditions were tested: five time points and three different IPTG and 3-AT concentrations. We find that GRaMS analysis is robust to the different experimental parameters whereas other analysis methods give widely varying results depending on the conditions of the experiment. Finally, we demonstrate that the CV-B1H assay can be performed in liquid media, which produces recognition models that are similar in quality to sequences recovered from selection on solid media

An on-bead tailing/ligation approach for sequencing resin-bound RNA libraries

Nucleic acids possess the unique property of being enzymatically amplifiable, and have therefore been a popular choice for the combinatorial selection of functional sequences, such as aptamers or ribozymes. However, amplification typically requires known sequence segments that serve as primer binding sites, which can be limiting for certain applications, like the screening of on-bead libraries. Here, we report a method to amplify and sequence on-bead RNA libraries that requires not more than five known nucleotides. A key element is the attachment of the starting nucleoside to the synthesis resin via the nucleobase, which leaves the 3′-OH group accessible to subsequent enzymatic manipulations. After split-and-mix synthesis of the oligonucleotide library and deprotection, a poly(A)-tail can be efficiently added to this free 3′-hydroxyl terminus by Escherichia coli poly(A) polymerase that serves as an anchored primer binding site for reverse transcription. The cDNA is joined to a DNA adapter by T4 DNA ligase. PCR amplification yielded single-band products that could be cloned and sequenced starting from individual polystyrene beads. The method described here makes the selection of functional RNAs from on-bead RNA libraries more attractive due to increased flexibility in library design, higher yields of full-length sequence on bead and robust sequence determination