Incorporation of Half-Cycle Theory Into Ko Aging Theory for Aerostructural Flight-Life Predictions

The half-cycle crack growth theory was incorporated into the Ko closed-form aging theory to improve accuracy in the predictions of operational flight life of failure-critical aerostructural components. A new crack growth computer program was written for reading the maximum and minimum loads of each half-cycle from the random loading spectra for crack growth calculations and generation of in-flight crack growth curves. The unified theories were then applied to calculate the number of flights (operational life) permitted for B-52B pylon hooks and Pegasus adapter pylon hooks to carry the Hyper-X launching vehicle that air launches the X-43 Hyper-X research vehicle. A crack growth curve for each hook was generated for visual observation of the crack growth behavior during the entire air-launching or captive flight. It was found that taxiing and the takeoff run induced a major portion of the total crack growth per flight. The operational life theory presented can be applied to estimate the service life of any failure-critical structural components

Robots in Retirement Homes: Applying Off-the-Shelf Planning and Scheduling to a Team of Assistive Robots

This paper investigates three different technologies for solving a planning and scheduling problem of deploying multiple robots in a retirement home environment to assist elderly residents. The models proposed make use of standard techniques and solvers developed in AI planning and scheduling, with two primary motivations. First, to find a planning and scheduling solution that we can deploy in our real-world application. Second, to evaluate planning and scheduling technology in terms of the ``model-and-solve'' functionality that forms a major research goal in both domain-independent planning and constraint programming. Seven variations of our application are studied using the following three technologies: PDDL-based planning, time-line planning and scheduling, and constraint-based scheduling. The variations address specific aspects of the problem that we believe can impact the performance of the technologies while also representing reasonable abstractions of the real world application. We evaluate the capabilities of each technology and conclude that a constraint-based scheduling approach, specifically a decomposition using constraint programming, provides the most promising results for our application. PDDL-based planning is able to find mostly low quality solutions while the timeline approach was unable to model the full problem without alterations to the solver code, thus moving away from the model-and-solve paradigm. It would be misleading to conclude that constraint programming is ``better'' than PDDL-based planning in a general sense, both because we have examined a single application and because the approaches make different assumptions about the knowledge one is allowed to embed in a model. Nonetheless, we believe our investigation is valuable for AI planning and scheduling researchers as it highlights these different modelling assumptions and provides insight into avenues for the application of AI planning and scheduling for similar robotics problems. In particular, as constraint programming has not been widely applied to robot planning and scheduling in the literature, our results suggest significant untapped potential in doing so.California Institute of Technology. Keck Institute for Space Studie

Towards Quantum Belief Propagation for LDPC Decoding in Wireless Networks

We present Quantum Belief Propagation (QBP), a Quantum Annealing (QA) based decoder design for Low Density Parity Check (LDPC) error control codes, which have found many useful applications in Wi-Fi, satellite communications, mobile cellular systems, and data storage systems. QBP reduces the LDPC decoding to a discrete optimization problem, then embeds that reduced design onto quantum annealing hardware. QBP's embedding design can support LDPC codes of block length up to 420 bits on real state-of-the-art QA hardware with 2,048 qubits. We evaluate performance on real quantum annealer hardware, performing sensitivity analyses on a variety of parameter settings. Our design achieves a bit error rate of $10^{-8}$ in 20 $\mu$s and a 1,500 byte frame error rate of $10^{-6}$ in 50 $\mu$s at SNR 9 dB over a Gaussian noise wireless channel. Further experiments measure performance over real-world wireless channels, requiring 30 $\mu$s to achieve a 1,500 byte 99.99$\%$ frame delivery rate at SNR 15-20 dB. QBP achieves a performance improvement over an FPGA based soft belief propagation LDPC decoder, by reaching a bit error rate of $10^{-8}$ and a frame error rate of $10^{-6}$ at an SNR 2.5--3.5 dB lower. In terms of limitations, QBP currently cannot realize practical protocol-sized ($\textit{e.g.,}$ Wi-Fi, WiMax) LDPC codes on current QA processors. Our further studies in this work present future cost, throughput, and QA hardware trend considerations

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

The polymyxin antibiotics [colistin and polymyxin B (PMB)] are increasingly used as a last-line option for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria. Despite having similar structures and antibacterial activity in vitro, the two clinically available polymyxins have very different pharmacological properties, as colistin (polymyxin E) is intravenously administered to patients in the form of an inactive prodrug colistin methanesulphonate (sodium). This review will discuss recent progress in the pharmacokinetics/pharmacodynamics and toxicity of colistin and PMB, the factors that affect their pharmacological profiles, and the challenges for the effective use of both polymyxins. Strategies are proposed for optimising their clinical utility based upon the recent pharmacological studies in vitro, in animals and patients. In the ‘bad bugs, no drugs’ era, polymyxins are a critically important component of the antibiotic armamentarium against difficult-to-treat Gram-negative ‘superbugs’. Rational approaches to the use of polymyxins must be pursued to increase their effectiveness and to minimise resistance and toxicity

Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance

Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise. However, the precise mechanisms by which exercise and ROS promote metabolic health remain unclear. Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance. Conversely, reductions in skeletal muscle NOX4 in aging and obesity contribute to the development of insulin resistance. NOX4 deletion in skeletal muscle compromised exercise capacity and antioxidant defense and promoted oxidative stress and insulin resistance in aging and obesity. The abrogated adaptive mechanisms, oxidative stress, and insulin resistance could be corrected by deleting the H2O2-detoxifying enzyme GPX-1 or by treating mice with an agonist of NFE2L2, the master regulator of antioxidant defense. These findings causally link NOX4-derived ROS in skeletal muscle with adaptive responses that promote muscle function and insulin sensitivity

Inequalities and Agencies in Workplace Learning Experiences: International Student Perspectives

The final publication is available at Springer via http://dx.doi.org/10.1007/s12186-016-9167-2National systems of vocational education and training around the globe are facing reform driven by quality, international mobility, and equity. Evidence suggests that there are qualitatively distinctive challenges in providing and sustaining workplace learning experiences to international students. However, despite growing conceptual and empirical work, there is little evidence of the experiences of these students undertaking workplace learning opportunities as part of vocational education courses. This paper draws on a four-year study funded by the Australian Research Council that involved 105 in depth interviews with international students undertaking work integrated learning placements as part of vocational education courses in Australia. The results indicate that international students can experience different forms of discrimination and deskilling, and that these were legitimised by students in relation to their understanding of themselves as being an ‘international student’ (with fewer rights). However, the results also demonstrated the ways in which international students exercised their agency towards navigating or even disrupting these circumstances, which often included developing their social and cultural capital. This study, therefore, calls for more proactively inclusive induction and support practices that promote reciprocal understandings and navigational capacities for all involved in the provision of work integrated learning. This, it is argued, would not only expand and enrich the learning opportunities for international students, their tutors, employers, and employees involved in the provision of workplace learning opportunities, but it could also be a catalyst to promote greater mutual appreciation of diversity in the workplace

T-BET and EOMES sustain mature human NK cell identity and antitumor function

Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which was rapidly lost following T-BET and EOMES deletion. Further, T-BET- and EOMES-deleted CD56bright NK cells acquired an innate lymphoid cell precursor-like (ILCP-like) profile with increased expression of the ILC-3-associated TFs RORC and AHR, revealing a role for T-box TFs in maintaining mature NK cell phenotypes and an unexpected role of suppressing alternative ILC lineages. Our study reveals the critical importance of sustained EOMES and T-BET expression to orchestrate mature NK cell function and identity

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies