Finding your way into an open online learning community

Making educational materials freely available on the web is not only a noble enterprise, but also fits the call of helping people to become lifelong learners; a call which gets louder and louder every day. The world is rapidly changing, requiring us to continuously update our knowledge and skills. A problem with this approach to lifelong learning is that the materials that are made available are often both incomplete and unsuitable for independent learning in an online setting. The OpenER (Open Educational Resources) project at the Open Universiteit Nederland makes more than 20 short courses, originally developed for independent-study, freely available from the website www.opener.ou.nl. For our research we start from an envisioned online learning environment now under development. We use backcasting to select research topics that form steps from the current to the ultimate situation. The two experiments we report on here are an extension to standard forum software and the use of student notes to annotate learning materials: two small steps towards our ultimate open learning environment

Fouling mechanisms in constant flux crossflow ultrafiltration

Four fouling models due to Hermia (complete pore blocking, intermediate pore blocking, cake filtration and standard pore blocking), have long been used to describe membrane filtration and fouling in constant transmembrane pressure (ΔP) operation of membranes. A few studies apply these models to constant flux dead-end filtration systems. However, these models have not been reported for constant flux crossflow filtration, despite the frequent use of this mode of membrane operation in practical applications. We report derivation of these models for constant flux crossflow filtration. Of the four models, complete pore blocking and standard pore blocking were deemed inapplicable due to contradicting assumptions and relevance, respectively. Constant flux crossflow fouling experiments of dilute latex bead suspensions and soybean oil emulsions were conducted on commercial poly (ether sulfone) flat sheet ultrafiltration membranes to explore the models’ abilities to describe such data. A model combining intermediate pore blocking and cake filtration appeared to give the best agreement with the experimental data. Below the threshold flux, both the intermediate pore blocking model and the combined model fit the data well. As permeate flux approached and passed the threshold flux, the combined model was required for accurate fits. Based on this observation, a physical interpretation of the threshold flux is proposed: the threshold flux is the flux below which cake buildup is negligible and above which cake filtration becomes the dominant fouling mechanism

Thermal Spore Exposure Vessels

Thermal spore exposure vessels (TSEVs) are laboratory containers designed for use in measuring rates of death or survival of microbial spores at elevated temperatures. A major consideration in the design of a TSEV is minimizing thermal mass in order to minimize heating and cooling times. This is necessary in order to minimize the number of microbes killed before and after exposure at the test temperature, so that the results of the test accurately reflect the effect of the test temperature. A typical prototype TSEV (see figure) includes a flat-bottomed stainless-steel cylinder 4 in. (10.16 cm) long, 0.5 in. (1.27 cm) in diameter, having a wall thickness of 0.010 plus or minus 0.002 in. (0.254 plus or minus 0.051 mm). Microbial spores are deposited in the bottom of the cylinder, then the top of the cylinder is closed with a sterile rubber stopper. Hypodermic needles are used to puncture the rubber stopper to evacuate the inside of the cylinder or to purge the inside of the cylinder with a gas. In a typical application, the inside of the cylinder is purged with dry nitrogen prior to a test. During a test, the lower portion of the cylinder is immersed in a silicone-oil bath that has been preheated to and maintained at the test temperature. Test temperatures up to 220 C have been used. Because the spores are in direct contact with the thin cylinder wall, they quickly become heated to the test temperature

Modelling pulsed immunotherapy of tumour-immune interaction

We develop a mathematical model that describes the tumour-immune interaction and the effect on it of pulsed immunotherapy, based on the administration of adoptive cellular immunotherapy (ACI) combined with interleukin-2 (IL-2). The stability conditions for the tumour-free periodic solution are provided with different frequencies of ACI applications and IL-2 infusions. Furthermore, the effects of period, dosage and times of drug deliveries on the amplitudes of the tumour-free periodic solution were investigated. The most feasible immunotherapy strategy was determined by comparing immunotherapy with ACI treatment with or without IL-2. However, to investigate how to enhance the efficacy of chemotherapy (radiotherapy) and reduce its sideeffects, we developed a model involving periodic applications of immunotherapy with chemotherapy (radiotherapy) applied only when the density of the tumour reached a given threshold. The results revealed that the initial densities, the effector cell: tumour cell ratios, the periods T and a given critical number of tumour cells CT are crucial for cancer treatment, which confirms that it is important to customise treatment strategies for individual patients

The Urgent Need for Global Nuclear Disarmament: An Occupational Therapy Perspective

The risk of nuclear war, exacerbated by recent global conflict, poses an existential threat to humanity and undermines the ability of individuals and communities to engage in meaningful occupation. This article argues that occupational therapists and occupational therapy assistants have a role to play in supporting global nuclear disarmament and that such efforts align with both our ethical responsibilities and scope of practice. It explores the profound impact of nuclear weapons on health and well-being, emphasizing the relevance of this issue to occupational therapy. The article outlines practical strategies for occupational therapists to engage in advocacy, including public education campaigns, professional alignment with disarmament organizations, and direct support for affected communities. By advocating for nuclear disarmament, occupational therapists can uphold their commitment to enhancing global health and participation, contributing to a safer and more peaceful world. This call to action highlights the role of occupational therapy in addressing the catastrophic potential of nuclear weapons and promoting a future where everyone can safely and meaningfully engage in their daily lives

A high-order Boris integrator

This work introduces the high-order Boris-SDC method for integrating the equations of motion for electrically charged particles in electric and magnetic fields. Boris-SDC relies on a combination of the Boris-integrator with spectral deferred corrections (SDC). SDC can be considered as preconditioned Picard iteration to compute the stages of a collocation method. In this interpretation, inverting the preconditioner corresponds to a sweep with a low-order method. In Boris-SDC, the Boris method, a second-order Lorentz force integrator based on velocity-Verlet, is used as a sweeper/preconditioner. The presented method provides a generic way to extend the classical Boris integrator, which is widely used in essentially all particle-based plasma physics simulations involving magnetic fields, to a high-order method. Stability, convergence order and conservation properties of the method are demonstrated for different simulation setups. Boris-SDC reproduces the expected high order of convergence for a single particle and for the center-of-mass of a particle cloud in a Penning trap and shows good long-term energy stability

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

Development of Rural Leadership: Problems, Procedures, and Insights

Between 1965 and 1976, more than 700 rural leaders participated in one of four statewide public affairs leadership development programs. These programs were conducted by educational institutions in Pennsylvania, California, Michigan, and Montana. The W. K. Kellogg Foundation provided over $4 million in financial assistance. The programs were designed to: increase participation in public affairs by men and women from rural areas; improve problem-solving and leadership skills of participants; and encourage sponsoring educational institutions to expand their extension programs in the areas of public affairs education and rural leadership developent. The question that concerned educational policymakers and led to and guided this study was: How did these programs affect the participants and the involved institutions? This summary booklet is organized around four case studies. Chapter I provides an analytical review of both past and current assessments of the four statewide leadership development programs. Chapters II through V discuss the programs and findings of the projects conducted in Pennsylvania, California, Michigan,and Montana. The final chapter (VI) presents the results of a multivariate analysis of the outcomes and includes a discussion of the lessons learned as a result of conducting the study

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000