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BackgroundImproving access to end-of-life symptom control interventions among cancer patients is a public health priority in Tanzania, and innovative community-based solutions are needed. Mobile health technology holds promise; however, existing resources are limited, and outpatient access to palliative care specialists is poor. A mobile platform that extends palliative care specialist access via shared care with community-based local health workers (LHWs) and provides remote support for pain and other symptom management can address this care gap. ObjectiveThe aim of this study is to design and develop mobile-Palliative Care Link (mPCL), a web and mobile app to support outpatient symptom assessment and care coordination and control, with a focus on pain. MethodsA human-centered iterative design framework was used to develop the mPCL prototype for use by Tanzanian palliative care specialists (physicians and nurses trained in palliative care), poor-prognosis cancer patients and their lay caregivers (patients and caregivers), and LHWs. Central to mPCL is the validated African Palliative Care Outcome Scale (POS), which was adapted for automated, twice-weekly collection of quality of life–focused patient and caregiver responses and timely review, reaction, and tracking by specialists and LHWs. Prototype usability testing sessions were conducted in person with 21 key informants representing target end users. Sessions consisted of direct observations and qualitative and quantitative feedback on app ease of use and recommendations for improvement. Results were applied to optimize the prototype for subsequent real-world testing. Early pilot testing was conducted by deploying the app among 10 patients and caregivers, randomized to mPCL use versus phone-contact POS collection, and then gathering specialist and study team feedback to further optimize the prototype for a broader randomized field study to examine the app’s effectiveness in symptom control among cancer patients. ResultsmPCL functionalities include the ability to create and update a synoptic clinical record, regular real-time symptom assessment, patient or caregiver and care team communication and care coordination, symptom-focused educational resources, and ready access to emergency phone contact with a care team member. Results from the usability and pilot testing demonstrated that all users were able to successfully navigate the app, and feedback suggests that mPCL has clinical utility. User-informed recommendations included further improvement in app navigation, simplification of patient and caregiver components and language, and delineation of user roles. ConclusionsWe designed, built, and tested a usable, functional mobile app prototype that supports outpatient palliative care for Tanzanian patients with cancer. mPCL is expressly designed to facilitate coordinated care via customized interfaces supporting core users—patients or caregivers, LHWs, and members of the palliative care team—and their respective roles. Future work is needed to demonstrate the effectiveness and sustainability of mPCL to remotely support the symptom control needs of Tanzanian cancer patients, particularly in harder-to-reach areas.

Adaptive learning has become more popular over the last several years, especially with the increasing need to adapt to students with different needs, interests, and learning preferences. The aim of adaptive learning is to provide students with the means to acquire information according to their training needs and cognitive differences, thus facilitating the learning process of each individual. Adaptive learning can be defined as an individualized adaptation of content and pedagogy implementation according to the needs of participants to increase the effectiveness and quality of learning. In this paper, we evaluate the available literature on adaptive learning technology using a SWOT (strengths, weaknesses, opportunities, and threats) approach. While there is promise in adaptive learning, much work still exists in helping to define best practices for utilizing adaptive learning technology to improve student learning and the student experience.

Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI(+) bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighboring target bacteria and produce CDI immunity proteins (CdiI) to protect against self-inhibition. The CdiA-CT(EC536) deployed by uropathogenic Escherichia coli 536 (EC536) is a bacterial toxin 28 (Ntox28) domain that only exhibits ribonuclease activity when bound to the cysteine biosynthetic enzyme O-acetylserine sulfhydrylase A (CysK). Here, we present crystal structures of the CysK/CdiA-CT(EC536) binary complex and the neutralized ternary complex of CysK/CdiA-CT/CdiI(EC536) CdiA-CT(EC536) inserts its C-terminal Gly-Tyr-Gly-Ile peptide tail into the active-site cleft of CysK to anchor the interaction. Remarkably, E. coli serine O-acetyltransferase uses a similar Gly-Asp-Gly-Ile motif to form the "cysteine synthase" complex with CysK. The cysteine synthase complex is found throughout bacteria, protozoa, and plants, indicating that CdiA-CT(EC536) exploits a highly conserved protein-protein interaction to promote its toxicity. CysK significantly increases CdiA-CT(EC536) thermostability and is required for toxin interaction with tRNA substrates. These observations suggest that CysK stabilizes the toxin fold, thereby organizing the nuclease active site for substrate recognition and catalysis. By contrast, Ntox28 domains from Gram-positive bacteria lack C-terminal Gly-Tyr-Gly-Ile motifs, suggesting that they do not interact with CysK. We show that the Ntox28 domain from Ruminococcus lactaris is significantly more thermostable than CdiA-CT(EC536), and its intrinsic tRNA-binding properties support CysK-independent nuclease activity. The striking differences between related Ntox28 domains suggest that CDI toxins may be under evolutionary pressure to maintain low global stability.

Contact-dependent growth inhibition (CDI) is a widespread mechanism of inter-bacterial competition mediated by the CdiB/CdiA family of two-partner secretion proteins. CdiA effectors carry diverse C-terminal toxin domains (CdiA-CT), which are delivered into neighboring target cells to inhibit growth. CDI(+) bacteria also produce CdiI immunity proteins that bind specifically to cognate CdiA-CT toxins and protect the cell from auto-inhibition. Here, we compare the structures of homologous CdiA-CT/CdiI complexes from Escherichia coli EC869 and Yersinia pseudotuberculosis YPIII to explore the evolution of CDI toxin/immunity protein interactions. Both complexes share an unusual β-augmentation interaction, in which the toxin domain extends a β-hairpin into the immunity protein to complete a six-stranded anti-parallel sheet. However, the specific contacts differ substantially between the two complexes. The EC869 β-hairpin interacts mainly through direct H-bond and ion-pair interactions, whereas the YPIII β-hairpin pocket contains more hydrophobic contacts and a network of bridging water molecules. In accord with these differences, we find that each CdiI protein only protects target bacteria from its cognate CdiA-CT toxin. The compact β-hairpin binding pocket within the immunity protein represents a tractable system for the rationale design of small molecules to block CdiA-CT/CdiI complex formation. We synthesized a macrocyclic peptide mimic of the β-hairpin from EC869 toxin and solved its structure in complex with cognate immunity protein. These latter studies suggest that small molecules could potentially be used to disrupt CDI toxin/immunity complexes.

Mycobacterium heme utilization degrader (MhuD) is a heme-degrading protein from Mycobacterium tuberculosis responsible for extracting the essential nutrient iron from host-derived heme. MhuD has been previously shown to produce unique organic products compared to those of canonical heme oxygenases (HOs) as well as those of the IsdG/I heme-degrading enzymes from Staphylococcus aureus. Here, we report the X-ray crystal structure of cyanide-inhibited MhuD (MhuD-heme-CN) as well as detailed (1)H nuclear magnetic resonance (NMR), UV/vis absorption, and magnetic circular dichroism (MCD) spectroscopic characterization of this species. There is no evidence for an ordered network of water molecules on the distal side of the heme substrate in the X-ray crystal structure, as was previously reported for canonical HOs. The degree of heme ruffling in the crystal structure of MhuD is greater than that observed for HO and less than that observed for IsdI. As a consequence, the Fe 3dxz-, 3dyz-, and 3dxy-based MOs are very close in energy, and the room-temperature (1)H NMR spectrum of MhuD-heme-CN is consistent with population of both a (2)Eg electronic state with a (dxy)(2)(dxz,dyz)(3) electron configuration, similar to the ground state of canonical HOs, and a (2)B2g state with a (dxz,dyz)(4)(dxy)(1) electron configuration, similar to the ground state of cyanide-inhibited IsdI. Variable temperature, variable field MCD saturation magnetization data establishes that MhuD-heme-CN has a (2)B2g electronic ground state with a low-lying (2)Eg excited state. Our crystallographic and spectroscopic data suggest that there are both structural and electronic contributions to the α-meso regioselectivity of MhuD-catalyzed heme cleavage. The structural distortion of the heme substrate observed in the X-ray crystal structure of MhuD-heme-CN is likely to favor cleavage at the α- and γ-meso carbons, whereas the spin density distribution may favor selective oxygenation of the α-meso carbon.

Contact-dependent growth inhibition (CDI) is one mechanism of inter-bacterial competition. CDI(+) cells export large CdiA effector proteins, which carry a variety of C-terminal toxin domains (CdiA-CT). CdiA-CT toxins are specifically neutralized by cognate CdiI immunity proteins to protect toxin-producing cells from autoinhibition. Here, we use structure determination to elucidate the activity of a CDI toxin from Enterobacter cloacae (ECL). The structure of CdiA-CT(ECL) resembles the C-terminal nuclease domain of colicin E3, which cleaves 16S ribosomal RNA to disrupt protein synthesis. In accord with this structural homology, we show that CdiA-CT(ECL) uses the same nuclease activity to inhibit bacterial growth. Surprisingly, although colicin E3 and CdiA(ECL) carry equivalent toxin domains, the corresponding immunity proteins are unrelated in sequence, structure, and toxin-binding site. Together, these findings reveal unexpected diversity among 16S rRNases and suggest that these nucleases are robust and versatile payloads for a variety of toxin-delivery platforms.

Since the 1950s, the Council of Europe has established conventions and information networks to enhance student mobility and qualification recognition in Europe. In contrast, Asia did not take this issue into consideration until 1983, when the UNESCO Regional Convention on the Recognition of Studies, Diplomas and Degrees in Higher Education in Asia and the Pacific (the "1983 Convention") was adopted. The recognition of a joint degree when the schools are in two different countries is even more challenging than for a conventional degree, because they do not belong to any single national higher education system. The first purpose of this study is to describe the current situation in the recognition of foreign qualifications in higher education institutions in Europe and Asia. Next, schemes, procedures and challenges for recognizing a joint degree will be analyzed. The role of recognition bodies and quality assurance agencies in qualification recognition will be discussed at the end of the paper.

Mycobacterium tuberculosis must import iron from its host for survival, and its siderophore-dependent iron acquisition pathways are well established. Here we demonstrate a newly characterized pathway, whereby M. tuberculosis can use free heme and heme from hemoglobin as an iron source. Significantly, we identified the genomic region, Rv0202c-Rv0207c, responsible for the passage of heme iron across the mycobacterial membrane. Key players of this heme uptake system were characterized including a secreted protein and two transmembrane proteins, all three specific to mycobacteria. Furthermore, the crystal structure of the key heme carrier protein Rv0203 was found to have a unique fold. The discovery of a unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.

Students get a sense of realistic values for physical situations from texts, but more importantly from solving problems. Therefore, problems should use realistic values for quantities to provide needed practice. Unfortunately, some problems on tests and in textbooks do not use realistic values. Physical situations in electrostatics seem to be particularly problematic.

Tertiary education institutions are currently learning to integrate and balance the needs of varying stakeholders, including local students, national governments, and the global market. These three dimensions combine into the concept of a "glonacal"--global?+?national?+?local--region of higher education. At the same time, quality assurance influences higher education in terms of policy decisions and processes, putting more emphasis on teaching as a core function of universities, and leading to an increased bureaucratization and heavier administrative workload. Yet, there is little evidence of the consequences of the glonacal approach for the quality of teaching and learning within universities and colleges. The main purpose of this paper is to assess the impact of the glonacal quality assurance system of Asian higher education through a case study of the effects of three program accreditations on higher education institutions in Taiwan (Higher Education Evaluation & Accreditation Council of Taiwan [HEEACT], Association to Advance Collegiate Schools of Business International [AACSB International] and Institute of Engineering Education Taiwan [IEET]).

Various experiments and demonstrations relate air pressure and air pressure difference to force and area. Carpenter and Minnix describe a large-scale pneumatic lift in which a person sitting on a board atop a plastic garbage bag is lifted when the bag is connected to the exhaustport of a vacuum cleaner, which easily lifts the person. This article describes the construction and use of an inexpensive hand-held pneumatic lift to demonstrate the same principle.

As the numbers of international students have grown, higher education institutions in Asia have offered a growing range of English medium instruction (EMI) degree programs. But Asian governments and higher education institutions have not thought deeply about how to ensure quality of English medium instruction degree programs. At the same time, their accreditors have not been fully aware of how to establish an external quality assurance mechanism to measure the quality of these programs. This study's main purpose is to put the quality of the EMI degree programs of Taiwan higher education institutions into the perspective of the Taiwan's institutions and one local Taiwan accreditor. With both qualitative and quantitative approaches, a survey targeting Taiwan's colleges and universities and interviews of Higher Education Evaluation & Accreditation Council of Taiwan international reviewers and Asian higher education experts are used to examine the challenges of EMI implementation in Taiwan universities and the role of local accreditors playing in reviewing the English medium instruction degree programs.

In order to help students make well-informed choices, reliable college ranking systems with comparable information about higher education institutions worldwide have been welcomed by many students. Because traditional college rankings had many methodological problems, a new type of user-based ranking, called "personalized college ranking" started to develop in many nations in the late 1990s. In 2008, Higher Education Evaluation and Accreditation Council of Taiwan (HEEACT), launched a ranking project called "College Navigator in Taiwan" which developed the first Asian student-based college search engine to provide local and international students with transparent information on Taiwan's higher education institutions. The main objective of this paper, therefore, is to compare the rational, strategies and pathways for establishing personalized college rankings. In order to analyze the gap between students' preferences and university presidents' concerns over ranking indicators, HEEACT's "College Navigator in Taiwan" is adopted as a case study at the end of paper.

Since the start of the twenty-first century, university rankings have become internationalized. Global rankings have a variety of uses, levels of popularity and rationales and they are here to stay. An examination of the results of the current global ranking reveals that well-reputed world-class universities are amongst the top ranked ones. A major concern for university administrators in many parts of the world is how to use the global rankings wisely in their mid-term and long-term strategic planning for building their institutions into world-class universities. Four major global rankings have been developed: the Academic Ranking of World Universities, the World University Rankings, the Webometrics Ranking of World Universities and the Performance Ranking of Scientific Papers for World Universities. The main purpose of this paper is to explore the most influential indicators in these global university rankings that will affect the rank mobility of an institution. Based on an analysis of correlation coefficients and K-means clustering, a model of strategic institutional planning for building a world-class university is proposed. (Contains 14 tables and 1 figure.)

How influential has the "US News" Best Colleges ranking been over the last twenty-five years since it was first started in 1983? In what ways does this influence manifest itself? There is strong evidence of the impact of the US News rankings among consumers, prospective students and their parents, and the higher education establishment in the United States. Their influence has now gone global since the US News rankings, according to some, have been the model for what has become a worldwide trend. This paper will look at all of these effects. (Contains 2 footnotes.)

Computer interfaced electrostatic charge sensors allow both qualitative and quantitative measurements of electrostatic charge but are quite sensitive to charges accumulating on modern synthetic materials. They need to be used with care so that students can correctly interpret their measurements. This paper describes the operation of the sensors, precautions for using them, and suggestions for experiments with sample readings.

The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models of SMA, we observed widespread perturbations in ubiquitin homeostasis, including reduced levels of ubiquitin-like modifier activating enzyme 1 (UBA1). SMN physically interacted with UBA1 in neurons, and disruption of Ubal mRNA splicing was observed in the spinal cords of SMA mice exhibiting disease symptoms. Pharmacological or genetic suppression of UBA1 was sufficient to recapitulate an SMAlike neuromuscular pathology in zebrafish, suggesting that UBA1 directly contributes to disease pathogenesis. Dysregulation of UBA1 and subsequent ubiquitination pathways led to β-catenin accumulation, and pharmacological inhibition of β-catenin robustly ameliorated neuromuscular pathology in zebrafish, Drosophila, and mouse models of SMA. UBA1-associated disruption of β-catenin was restricted to the neuromuscular system in SMA mice; therefore, pharmacological inhibition of β-catenin in these animals failed to prevent systemic pathology in peripheral tissues and organs, indicating fundamental molecular differences between neuromuscular and systemic SMA pathology. Our data indicate that SMA-associated reduction of UBA1 contributes to neuromuscular pathogenesis through disruption of ubiquitin homeostasis and subsequent β-catenin signaling, highlighting ubiquitin homeostasis and β-catenin as potential therapeutic targets for SMA., Introduction Proximal spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, with a carrier frequency of 1 in 35 in the population of mixed European descent and [...]

In Benjamin Franklin's one fluid theory of electrification, ordinary unelectrified matter consisted of a matrix of matter suffused with a certain amount of "electrical fluid." Electrical effects were due to an excess or deficit of electrical fluid, hence the terms positive and negative. Before the development of a modern view of the atom, diagrams showing charged objects would simply have "+" or "-" signs to indicate the charged state. As physicists we know how to interpret these diagrams and understand what they are telling us about the underlying atomic model of charging. However, novice students may not readily make the connection between the atomic model, in which a charged solid object either gains or loses electrons but does not gain or lose positive charges. Furthermore, when isolated objects become charged, the total number of electrons must be accounted for as charge is a conserved quantity. To really understand the changes that occur in charging by contact, conduction, or induction, it is useful for students to visually represent the processes in a way that emphasizes the atomicity of the processes, including the induced polarization of objects, and the requirement that charge be conserved.