Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Communication style and exercise compliance in physiotherapy (CONNECT). A cluster randomized controlled trial to test a theory-based intervention to increase chronic low back pain patients’ adherence to physiotherapists’ recommendations: study rationale, design, and methods

Physical activity and exercise therapy are among the accepted clinical rehabilitation guidelines and are recommended self-management strategies for chronic low back pain. However, many back pain sufferers do not adhere to their physiotherapist’s recommendations. Poor patient adherence may decrease the effectiveness of advice and home-based rehabilitation exercises. According to self-determination theory, support from health care practitioners can promote patients’ autonomous motivation and greater long-term behavioral persistence (e.g., adherence to physiotherapists’ recommendations). The aim of this trial is to assess the effect of an intervention designed to increase physiotherapists’ autonomy-supportive communication on low back pain patients’ adherence to physical activity and exercise therapy recommendations. \ud \ud This study will be a single-blinded cluster randomized controlled trial. Outpatient physiotherapy centers (N =12) in Dublin, Ireland (population = 1.25 million) will be randomly assigned using a computer-generated algorithm to either the experimental or control arm. Physiotherapists in the experimental arm (two hospitals and four primary care clinics) will attend eight hours of communication skills training. Training will include handouts, workbooks, video examples, role-play, and discussion designed to teach physiotherapists how to communicate in a manner that promotes autonomous patient motivation. Physiotherapists in the waitlist control arm (two hospitals and four primary care clinics) will not receive this training. Participants (N = 292) with chronic low back pain will complete assessments at baseline, as well as 1 week, 4 weeks, 12 weeks, and 24 weeks after their first physiotherapy appointment. Primary outcomes will include adherence to physiotherapy recommendations, as well as low back pain, function, and well-being. Participants will be blinded to treatment allocation, as they will not be told if their physiotherapist has received the communication skills training. Outcome assessors will also be blinded. \ud \ud We will use linear mixed modeling to test between arm differences both in the mean levels and the rates of change of the outcome variables. We will employ structural equation modeling to examine the process of change, including hypothesized mediation effects. \ud \ud This trial will be the first to test the effect of a self-determination theory-based communication skills training program for physiotherapists on their low back pain patients’ adherence to rehabilitation recommendations. Current Controlled Trials ISRCTN63723433\u

An investigation to determine the static pressure distribution of the 0.00548 scale shuttle solid rocket booster (MSFC model number 468) during reentry in the NASA/MSFC 14 inch trisonic wind tunnel (SA28F)

The results of a pressure test of a .00548 scale 146 inch Space Shuttle Solid Rocket Booster (SRB) with and without protuberances, conducted in a 14 x 14 inch trisonic wind tunnel are presented. Static pressure distributions for the SRB at reentry attitudes and flight conditions were obtained. Local longitudinal and ring pressure distributions are presented in tabulated form. Integration of the pressure data was performed. The test was conducted at Mach numbers of 0.40 to 4.45 over an angle of attack range from 60 to 185 degrees. Roll angles of 0, 45, 90 and 315 degrees were investigated. Reynolds numbers per foot varied for selected Mach numbers

Crafting the Composite Garment: The role of hand weaving in digital creation

There is a growing body of practice-led textile research, focused on how digital technologies can inform new design and production strategies that challenge and extend the field. To date, this research has emphasized a traditional linear transition between hand and digital production; with hand production preceding digital as a means of acquiring the material and process knowledge required to negotiate technologies and conceptualize designs. This paper focuses on current Doctoral research into the design and prototyping of 3D woven or 'composite' garments and how the re-learning, or reinterpreting, of hand weaving techniques in a digital Jacquard format relies heavily on experiential knowledge of craft weaving skills. Drawing parallels between hand weaving and computer programming, that extend beyond their shared binary (pixel-based) language, the paper discusses how the machine-mediated experience of hand weaving can prime the weaver to ‘think digitally’ and make the transition to digital production. In a process where the weaver acts simultaneously as designer, constructor and programmer, the research explores the inspiring, but often indefinable space between craft and digital technology by challenging the notion that 'the relationship between hand, eye and material’ naturally precedes the use of computing (Harris 2012: 93). This is achieved through the development of an iterative working methodology that encompasses a cycle of transitional development, where hand weaving and digital processes take place in tandem, and techniques and skills are reinterpreted to exploit the advantages and constraints of each construction method. It is argued that the approach challenges the codes and conventions of computer programming, weaving and fashion design to offer a more sustainable clothing solution

Using a finite element grid on corner points in flow models

One of the main functions of a multilayer cover liner is to prevent water from infiltrating into mine or other waste thereby preventing the occurrence of ground water pollution. In the past, numerical models have predominantly dealt with vertical infiltration or infiltration into sloping hillsides of infinite extent. The two layer model investigated in this paper has a more realistic shape which is piece-wise linear with a horizontal top, vertical bottom and a sloping section in-between. At the intersection of these segments are corner points where there are changes from sloping flow dynamics to either vertical or horizontal flow dynamics, depending on the corner point. The abrupt change in dynamics at the corner points can cause numerical problems especially when dealing with the boundary condition at the interface of two soils. This paper will deal with the corner point problem at the soil layer interface and, in particular, investigate the use of a finite element grid around the corner points

Like It Is, Episode #329, Interview with Holmes Braddock

This episode of Like It Is , aired in 1980, features Holmes Braddock discussing the value of education, desegregation, and racial integration. Braddock emphasizes that education is a holistic process beyond classroom learning and advocates for equal educational opportunities for all races. He speaks of his support for busing and integration as means to break down segregation at the time and believed that genuine integration, where students interact and learn together, was progressing despite challenges. Braddock advocates for maintaining a commitment to law and fairness in desegregation efforts, and emphasizes the importance of respecting individual differences. He also discusses the need for Black and white students to interrelate and understand each other\u27s cultures, opposing the idea of separate Black institutions for K-12 education

Photochemical dihydrogen production using an analogue of the active site of [NiFe] hydrogenase

The photoproduction of dihydrogen (H2) by a low molecular weight analogue of the active site of [NiFe] hydrogenase has been investigated by the reduction of the [NiFe2] cluster, 1, by a photosensitier PS (PS = [ReCl(CO)3(bpy)] or [Ru(bpy)3][PF6]2). Reductive quenching of the 3MLCT excited state of the photosensitiser by NEt3 or N(CH2CH2OH)3 (TEOA) generates PS•−, and subsequent intermolecular electron transfer to 1 produces the reduced anionic form of 1. Time-resolved infrared spectroscopy (TRIR) has been used to probe the intermediates throughout the reduction of 1 and subsequent photocatalytic H2 production from [HTEOA][BF4], which was monitored by gas chromatography. Two structural isomers of the reduced form of 1 (1a•− and 1b•−) were detected by Fourier transform infrared spectroscopy (FTIR) in both CH3CN and DMF (dimethylformamide), while only 1a•− was detected in CH2Cl2. Structures for these intermediates are proposed from the results of density functional theory calculations and FTIR spectroscopy. 1a•− is assigned to a similar structure to 1 with six terminal carbonyl ligands, while calculations suggest that in 1b•− two of the carbonyl groups bridge the Fe centres, consistent with the peak observed at 1714 cm−1 in the FTIR spectrum for 1b•− in CH3CN, assigned to a ν(CO) stretching vibration. The formation of 1a•− and 1b•− and the production of H2 was studied in CH3CN, DMF and CH2Cl2. Although the more catalytically active species (1a•− or 1b•−) could not be determined, photocatalysis was observed only in CH3CN and DMF

What punishment expresses

In this article, I consider the question of what punishment expresses and propose a way of approaching the question that overcomes problems in both psychosocial and philosophical expressivist traditions. The problem in both traditions is, I suggest, the need for an adequate moral – neither moralizing nor reductive – psychology, and I argue that Melanie Klein’s work offers such a moral psychology. I offer a reconstruction of Klein’s central claims and begin to sketch some of its potential implications for an expressive account of punishment. I outline a Kleinian interpretation of modern punishment’s expression as of an essentially persecutory nature but also include depressive realizations that have generally proved too difficult for liberal modernity to work through successfully, and the recent ‘persecutory turn’ is a defence against such realizations. I conclude by considering the wider philosophical significance of a Kleinian account for the expressivist theory of punishment

Missing Links: Referrer Behavior and Job Segregation

How does referral recruitment contribute to job segregation, and what can organizations do about it? Current theory on network effects in the labor market emphasizes the job-seeker perspective, focusing on the segregated nature of job-seekers’ information and contact networks, and leaves little role for organizational influence. But employee referrals are necessarily initiated from within a firm by referrers. We argue that referrer behavior is the missing link that can help organizations manage the segregating effects of referring. Adopting the referrer’s perspective of the process, we develop a computational model which integrates a set of empirically documented referrer behavior mechanisms gleaned from extant organizational case studies. Using this model, we compare the segregating effects of referring when these behaviors are inactive to the effects when the behaviors are active. We show that referrer behaviors substantially boost the segregating effects of referring. This impact of referrer behavior presents an opportunity for organizations. Contrary to popular wisdom, we show that organizational policies designed to influence referrer behaviors can mitigate most if not all of the segregating effects of referring