How the structure of the large subunit controls function in an oxygen-tolerant [NiFe]-hydrogenase

Salmonella enterica is an opportunistic pathogen that produces a [NiFe]-hydrogenase under aerobic conditions. In the present study, genetic engineering approaches were used to facilitate isolation of this enzyme, termed Hyd-5. The crystal structure was determined to a resolution of 3.2 Å and the hydro-genase was observed to comprise associated large and small subunits. The structure indicated that His(229) from the large subunit was close to the proximal [4Fe–3S] cluster in the small subunit. In addition, His(229) was observed to lie close to a buried glutamic acid (Glu(73)), which is conserved in oxygen-tolerant hydrogenases. His(229) and Glu(73) of the Hyd-5 large subunit were found to be important in both hydrogen oxidation activity and the oxygen-tolerance mechanism. Substitution of His(229) or Glu(73) with alanine led to a loss in the ability of Hyd-5 to oxidize hydrogen in air. Furthermore, the H229A variant was found to have lost the overpotential requirement for activity that is always observed with oxygen-tolerant [NiFe]-hydrogenases. It is possible that His(229) has a role in stabilizing the super-oxidized form of the proximal cluster in the presence of oxygen, and it is proposed that Glu(73)could play a supporting role in fine-tuning the chemistry of His(229) to enable this function

To protect the hell yeah and every hell yeah\u27s variations

I try to imagine a scrutiny free from transaction and authority, where time and generosity are not scarce. If real generosity divests from the expectation of returns, then what are the full implications of imaging someone in this way, through touch? My sitters gave me permission to stare at them in private. What happens to this momentary consensual gaze over time, prolonged into months of looking? Prolonged into an abundance of labor, abundance of attention, abundance of precious materials

Re-engineering a NiFe hydrogenase to increase the H2 production bias while maintaining native levels of O2 tolerance

Naturally occurring oxygen tolerant NiFe membrane bound hydrogenases have a conserved catalytic bias towards hydrogen oxidation which limits their technological value. We present an Escherichia coli Hyd-1 amino acid exchange that apparently causes the catalytic rate of H2 production to double but does not impact the O2 tolerance

Technology as a resource: Increasing engagement in learning and developing 21st century skills

The purpose of this research study was to help inform the researcher’s future practice as a teacher on the influence of technology on young learners. The question of inquiry pertained to define how technology has initiated and increased student engagement within their learning, and through this, how technology has specifically influenced the creation of the 21st century learner. By beginning the inquiry through a literature review on the theme of technology and student engagement, the researcher was able to gain an understanding that technology is the motivator for children in developed, and even in undeveloped countries. In order to assess the relationship of technology and student engagement in learning, along with how digital devices influence the creation of 21st century learners, the researcher surveyed a variety of teacher candidates and university students to draw conclusions. From the research findings of the study, the researcher concluded that students were attracted to technology as it is a tool that is convenient in organizing information, and is efficient in making data easier to allocate. Therefore, the skills that technology imparted upon 21st century learners from the findings were allowing students to become self-directed learners, access and, evaluate information through critical thinking and solving data to become more engaged thinkers, and influencing leadership and collaboration skills

Demon or philosopher: the artist and teacher Tibor Varga

The Hungarian violinist and pedagogue Tibor Varga (1921–2003) was a performer of formidable technical ability whose playing was characterised by a vibrant and powerful tone and a unique approach to phrasing. He is rarely acknowledged among the great violinists of the twentieth century notwithstanding his legacy of compositions, recordings and teaching which indicates that the field of violin performance and education may have much to gain from his approach to playing and teaching. At this point, there is no comprehensive presentation of his contribution to violin playing and teaching. This research project presents and analyses Tibor Varga’s approach to performance and pedagogy and places it in the context of violin pedagogy from the seventeenth century to today. Significant influences are identified and the advantages and disadvantages of his technical conceptions, approach to practice, performance, and his psychology of teaching are discussed critically. Significant violin pedagogical literature, journal articles about Varga, interviews, literature on psychology in music education and direct information gathered in lessons is used to inform this investigation. Varga’s original contributions to the development of violin playing are presented and unique approaches to practice and performance are highlighted. The concept of an ‘old school’ of playing and teaching and its place in contemporary teaching that is the result of scientific research in the twentieth century is discussed. Encouraging students to think for themselves is identified as fundamental to a successful didactic approach and revealed as central to Tibor Varga’s philosophy of teaching

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

Shawn Hunt\u27s Transformation Mask: The Intersection of Contemporary and Traditional Heiltsuk Art

Shawn Hunt is an artist of Heiltsuk (Bella Bella), French, and Scottish Canadian ancestry who is at the forefront of contemporary Northwest Coast art in the Vancouver area. Historic artworks of his community have been often overlooked in scholarly literature due to the seeming willingness of the people to adapt to colonization. Viewed as a “tainted” culture, the Heiltsuk have been noticeably ignored in the art historical realm. However, their masks are some of the best examples of traditional regalia that are found in museums across Canada and the United States. Contemporary native artists of the Northwest Coast continue to use these works as examples for their own pieces today – these artists are merely continuing tradition in the modern day. Hunt is making strides towards blending the “traditional” and the “contemporary” native art worlds into an inclusive, more indigenous notion of art today. His works speak about indigenous identity and what the “authentic” native looks like today. Hunt’s work Transformation Mask is the best example of his work intersecting the boundaries of western categories of native art. He is able to blend the ideas of “native,” “contemporary,” and “traditional” through the utilization of oral histories, clan imagery, and commercial technologies. My thesis discusses Hunt’s work in relation to long-standing Heiltsuk art practices. It breaks new ground as the first in-depth examination of Hunt’s Transformation Mask which explores the issues of identity, respect for ceremony and expansion on traditions, and the resistance to colonial narratives