1,761 research outputs found

    Set‐Based Design and the Ship to Shore Connector

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    The Ship to Shore Connector (SSC), a replacement for the Landing Craft, Air Cushion (LCAC), is the first government‐led design of a ship in over 15 years. This paper will discuss the changes that a government‐led design presents to the design approach, including schedule, organization structure, and design methodology. While presenting challenges, a government‐led design also afforded the opportunity to implement a new technique for assessing various systems and ship alternatives, set‐based design (SBD). The necessity for implementing SBD was the desire to design SSC from a blank sheet of paper and the need for a replacement craft in a short time frame. That is, the LCACs need to be replaced and consequently the preliminary design phase of the SSC program will only be 12 months. This paper will describe SBD and how it was applied to the SSC, the challenges that the program faced, and an assessment of the new methodology, along with recommendations that future design programs should consider when adopting this approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90054/1/j.1559-3584.2011.00332.x.pd

    Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis

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    Muscle dysfunction is a common feature of severe sepsis and multi-organ failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP-3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit ROS production. Using a murine model, we examined metabolic, cardiovascular and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3(-/-) mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Mitochondrial membrane potential was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP-3 protein abundance at 24 hours, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3(-/-) mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and phosphorylation pathway. However, UCP-3 does not play an important functional role, despite its upregulation

    A note on monopole moduli spaces

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    We discuss the structure of the framed moduli space of Bogomolny monopoles for arbitrary symmetry breaking and extend the definition of its stratification to the case of arbitrary compact Lie groups. We show that each stratum is a union of submanifolds for which we conjecture that the natural L2L^2 metric is hyperKahler. The dimensions of the strata and of these submanifolds are calculated, and it is found that for the latter, the dimension is always a multiple of four.Comment: 17 pages, LaTe

    Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements

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    As they proliferate, living cells undergo transitions between specific molecularly and developmentally distinct states. Despite the functional centrality of these transitions in multicellular organisms, it has remained challenging to determine which transitions occur and at what rates without perturbations and cell engineering. Here, we introduce kin correlation analysis (KCA) and show that quantitative cell-state transition dynamics can be inferred, without direct observation, from the clustering of cell states on pedigrees (lineage trees). Combining KCA with pedigrees obtained from time-lapse imaging and endpoint single-molecule RNA-fluorescence in situ hybridization (RNA-FISH) measurements of gene expression, we determined the cell-state transition network of mouse embryonic stem (ES) cells. This analysis revealed that mouse ES cells exhibit stochastic and reversible transitions along a linear chain of states ranging from 2C-like to epiblast-like. Our approach is broadly applicable and may be applied to systems with irreversible transitions and non-stationary dynamics, such as in cancer and development

    Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

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    Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

    PySDM v1 : particle-based cloud modeling package for warm-rain microphysics and aqueous chemistry

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    PySDM is an open-source Python package for simulating the dynamics of particles undergoing condensational and collisional growth, interacting with a fluid flow and subject to chemical composition changes. It is intended to serve as a building block for process-level as well as computational-fluid-dynamics simulation systems involving representation of a continuous phase (air) and a dispersed phase (aerosol), with PySDM being responsible for representation of the dispersed phase. The PySDM package core is a Pythonic high-performance implementation of the Super-Droplet Method (SDM) Monte-Carlo algorithm for representing collisional growth, hence the name. PySDM has two alternative parallel number-crunching backends available: multi-threaded CPU backend based on Numba and GPU-resident backend built on top of ThrustRTC. The usage examples are built on top of four simple atmospheric cloud modelling frameworks: box, adiabatic parcel, single-column and 2D prescribed flow kinematic models. In addition, the package ships with tutorial code depicting how PySDM can be used from Julia and Matlab

    Weaving Academic Grace into the Fabric of Online Courses and Faculty Training: First-Year Engineering Student Advice for Online Faculty During the COVID-19 Pandemic and Faculty Responses

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    Background: In the spring of 2020, COVID-19 forced the majority of higher education online, resulting in a wave of new online students uniquely positioned to offer fresh perspectives and advice to faculty. Purpose: This study investigated the advice offered to online faculty by first-year engineering (FYE) students who were forced online during the pandemic and faculty ideas to address the student advice. Methods: This multi-methods study included qualitative data from 233 FYE students (in 67 teams across four class offerings) who provided advice for online faculty through an end-of-year team assignment, leveraging analytic induction methods for analysis. The Quality Matters Online Instructor Skill Set was used as the theoretical framework for viewing the student results (Quality Matters, 2016). After being presented with the student results, 41 faculty participants within two workshops brainstormed ways to respond to FYEs’ advice. Faculty workshop participants organized their own brainstorming/discussion results by themes within community documents. Results: Students forced online expressed the following needs/desires: instructional design practices appropriate for the online environment; understanding, flexibility, and patience from their faculty (which we defined as Academic Grace); instructor social presence; appropriate pedagogy for online learning environments; effective assessment; technologically capable instructors; and instructor understanding of their institutional context. Faculty advised responding to online students with more Academic Grace. Conclusions: This work reveals a new competency missing from traditional online instructor skills, that of Academic Grace. To embed Academic Grace within online courses, we propose that faculty consider a flexible bichronous model for online courses, in which students can choose to attend synchronous live lectures/classes or cover the material asynchronously at their own convenience. In this model, lecture/class recordings and supplemental asynchronous materials should be provided to foster fluid student movement between the learning modes. We also recommend online faculty training efforts include the components of Academic Grace: understanding, flexibility, and patience

    Signatures of natural selection between life cycle stages separated by metamorphosis in European eel

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    Received: 16 December 2014, Accepted: 6 July 2015, Published: 13 August 2015[Background] Species showing complex life cycles provide excellent opportunities to study the genetic associations between life cycle stages, as selective pressures may differ before and after metamorphosis. The European eel presents a complex life cycle with two metamorphoses, a first metamorphosis from larvae into glass eels (juvenile stage) and a second metamorphosis into silver eels (adult stage). We tested the hypothesis that different genes and gene pathways will be under selection at different life stages when comparing the genetic associations between glass eels and silver eels.[Results] We used two sets of markers to test for selection: first, we genotyped individuals using a panel of 80 coding-gene single nucleotide polymorphisms (SNPs) developed in American eel; second, we investigated selection at the genome level using a total of 153,423 RAD-sequencing generated SNPs widely distributed across the genome. Using the RAD approach, outlier tests identified a total of 2413 (1.57 %) potentially selected SNPs. Functional annotation analysis identified signal transduction pathways as the most over-represented group of genes, including MAPK/Erk signalling, calcium signalling and GnRH (gonadotropin-releasing hormone) signalling. Many of the over-represented pathways were related to growth, while others could result from the different conditions that eels inhabit during their life cycle.[Conclusions] The observation of different genes and gene pathways under selection when comparing glass eels vs. silver eels supports the adaptive decoupling hypothesis for the benefits of metamorphosis. Partitioning the life cycle into discrete morphological phases may be overall beneficial since it allows the different life stages to respond independently to their unique selection pressures. This might translate into a more effective use of food and niche resources and/or performance of phase-specific tasks (e.g. feeding in the case of glass eels, migrating and reproducing in the case of silver eels).We acknowledge funding from the Danish Council for Independent Reasearch, Natural Sciences (grant 09-072120 to MMH).Peer reviewe

    Research priorities of people living with Turner syndrome

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148393/1/ajmgc31676.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148393/2/ajmgc31676_am.pd
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