Retirees Look Back on the Years

Professors Howard Leichter, Linda Olds and Kareen Sturgeon share memories of their years at Linfield

Torque-dependent remodeling of the bacterial flagellar motor

Multisubunit protein complexes are ubiquitous in biology and perform a plethora of essential functions. Most of the scientific literature treats such assemblies as static: their function is assumed to be independent of their manner of assembly, and their structure is assumed to remain intact until they are degraded. Recent observations of the bacterial flagellar motor, among others, bring these notions into question. The torque-generating stator units of the motor assemble and disassemble in response to changes in load. Here, we used electrorotation to drive tethered cells forward, which decreases motor load, and measured the resulting stator dynamics. No disassembly occurred while the torque remained high, but all of the stator units were released when the motor was spun near the zero-torque speed. When the electrorotation was turned off, so that the load was again high, stator units were recruited, increasing motor speed in a stepwise fashion. A model in which speed affects the binding rate and torque affects the free energy of bound stator units captures the observed torque-dependent stator assembly dynamics, providing a quantitative framework for the environmentally regulated self-assembly of a major macromolecular machine

Parsnips in ELT: stepping out of the comfort zone (Vol. 2)

The PARSNIP is, as many of you will know, a reference to all those topics that are commonly left out of the standard ELT coursebook: Politics, Alcohol, Religion, Sex, Narcotics, -Isms, Pork. And it is easy to understand why these things are not included - in simple terms coursebooks are written for the largest possible market and therefore can only ever concentrate on the safest common denominator in terms of topics. You might be able to get away with a discussion on the differences between democratic governments and dictatorships in Portugal, but the chances are you might find it more difficult in Belarus. So if you want to sell a coursebook in both Portugal and Belarus, you have to make sure that the topics are not going to prove overly contentious or possibly lead to the arrest and deportation of the teacher and closing of the school. The result though, is what Mario Rinvolucri described as ““the soft, fudgey, sub-journalistic, woman’s magaziney world of EFLese course materials” - endless worthy discussions about the environment, the role of technology in life and how to have a healthy lifestyle. The Parsnips in ELT project is an attempt to provide resources and support for teachers who do want to engage their classes in more meaningful topics and discussions. Or at the very least to do something different! It is however, up to you and your own personal and professional judgment whether you choose to use these lesson plans in your context and with your classes, or even if you choose to read them at all! Inevitably, there will be some lessons that you will feel are inappropriate to use and some that you feel will really get the class engaged in the topic and the discussion

Bridging the gap between instructional design and double loop learning

Spoelstra, H., Matera, M., Rusman, E., Van Bruggen, J., & Koper, R. (2006). Bridging the gap between instructional design and double loop learning. Proceedings of IV International Conference on Multimedia and Information and Communication Technologies in Education (m-ICTE2006). November, 22-25, 2006, Seville, Spain.There seems to be a gap between instructional design, as implemented in workflow-like e-learning sys-tems, and double loop learning, because the former predefines educational processes and the latter as-sumes these processes can be reflected upon and can be modified by the learners. Instructional designs implemented in workflow-like e-learning systems that use modelling standards enable portability of the designs. While maintaining this advantage of portability, the COOPER environment aims to make room for learning reflection and influence as well. We will present a pedagogical scenario called “Virtual Com-pany”, which uses double loop learning extensively, to demonstrate the feasibility of our proposed solu-tion. We provide learners with “atomic actions”, that can be used to create and revise processes “on the fly”, thus enabling double-loop learning.This article is sponsored by the COOPER Project that is funded by the European Commission's 6th Framework Programme, priority 2 IST. Contract no.: 027073 (www.cooper-project.org

Observations on acoustic emissions from a line contact compressed into the plastic region

Some observations from acoustic emissions recorded during a yield test of a bearing raceway compressed into plasticity using a rolling element are presented. The general objective of the study is to establish whether there is enough evidence of the onset of sub-surface plasticity in the acoustic emissions signature. It is discussed here how acoustic emissions monitoring during compression could indicate the onset of subsurface plasticity as a precursor to damage propagation to the surface. Some comparisons are drawn between the acoustic emissions activity levels and time-frequency response during elastic deformation and at yield loads

Unfitness to Plead. Volume 1: Report.

This has been produced along with Volume 2: Draft Legislation as a combined document Presented to Parliament pursuant to section 3(2) of the Law Commissions Act 1965 Ordered by the House of Commons to be printed on 12 January 201

Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres

<p>Abstract</p> <p>Background</p> <p>It has been suggested that carbon nanotubes might conform to the fibre pathogenicity paradigm that explains the toxicities of asbestos and other fibres on a continuum based on length, aspect ratio and biopersistence. Some types of carbon nanotubes satisfy the first two aspects of the fibre paradigm but only recently has their biopersistence begun to be investigated. Biopersistence is complex and requires <it>in vivo </it>testing and analysis. However durability, the chemical mimicking of the process of fibre dissolution using <it>in vitro </it>treatment, is closely related to biopersistence and more readily determined. Here, we describe an experimental process to determine the durability of four types of carbon nanotubes in simulated biological fluid (Gambles solution), and their subsequent pathogenicity <it>in vivo </it>using a mouse model sensitive to inflammogenic effects of fibres. The <it>in vitro </it>and <it>in vivo </it>results were compared with well-characterised glass wool and asbestos fibre controls.</p> <p>Results</p> <p>After incubation for up to 24 weeks in Gambles solution, our control fibres were recovered at percentages consistent with their known <it>in vitro </it>durabilities and/or <it>in vivo </it>persistence, and three out of the four types of carbon nanotubes tested (single-walled (CNT_SW) and multi-walled (CNT_TANG2, CNT_SPIN)) showed no, or minimal, loss of mass or change in fibre length or morphology when examined by electron microscopy. However, the fourth type [multi-walled (CNT_LONG1)] lost 30% of its original mass within the first three weeks of incubation, after which there was no further loss. Electron microscopy of CNT_LONG1samples incubated for 10 weeks confirmed that the proportion of long fibres had decreased compared to samples briefly exposed to the Gambles solution. This loss of mass and fibre shortening was accompanied by a loss of pathogenicity when injected into the peritoneal cavities of C57Bl/6 mice compared to fibres incubated briefly. CNT_SWdid not elicit an inflammogenic effect in the peritoneal cavity assay used here.</p> <p>Conclusions</p> <p>These results support the view that carbon nanotubes are generally durable but may be subject to bio-modification in a sample-specific manner. They also suggest that pristine carbon nanotubes, either individually or in rope-like aggregates of sufficient length and aspect ratio, can induce asbestos-like responses in mice, but that the effect may be mitigated for certain types that are less durable in biological systems. Results indicate that durable carbon nanotubes that are either short or form tightly bundled aggregates with no isolated long fibres are less inflammogenic in fibre-specific assays.</p

Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: Evidence for pleiotropy

In the U.S.A., cocaine is the second most abused illicit drug. Variants within the CHRNB3-A6 gene cluster have been associated with cigarette consumption in several GWAS. These receptors represent intriguing candidates for the study of cocaine dependence because nicotinic receptors are thought to be involved in generalized addiction pathways. Using genotypic data from a GWAS of the Study of Addiction: Genetics and Environment (SAGE) dataset, we tested for association of CHRNB3-A6 SNPs with DSM-5 cocaine use disorder. Multiple SNPs in the region were significantly associated with increased risk of cocaine use disorder. Inclusion of the most significant SNP as a covariate in a linear regression model provided evidence for an additional independent signal within this locus for cocaine use disorder. These results suggest that the CHRNB3-A6 locus contains multiple variants affecting risk for vulnerability to cocaine and nicotine dependence as well as bipolar disorder, suggesting that they have pleiotropic effects

Data Census of a Geographically-Bounded Tweet Set to Enhance Common Operational Picture Tools

Location information is of particular importance to crisis informatics. The Twitter API provides several methods to assess a rough location and/or the specific latitude and longitude in which a post originated. This paper offers a comparison of location information provided by Twitter’s four geolocation methods. The study aggregates one month of data from the greater Cincinnati, Ohio metropolitan area and assesses the relative contribution that each method can make to common operational picture tools used by crisis informatics researchers. Results show that of 49,744 Tweets, 4% contained geotags, 85.2% contained a location in the users’ profile, and 3.5% contained no apparent location data, but were gathered using the bounding box method and would not have been identified using traditional methods of gathering data using geotagged Tweets or user profile information alone. We reflect on these results in light of design implications for common operational picture tools (COPs)

Current perspectives in fragment based lead discovery (FBLD)

It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems