Design of Launch Abort System Thrust Profile and Concept of Operations

This paper describes how the Abort Motor thrust profile has been tailored and how optimizing the Concept of Operations on the Launch Abort System (LAS) of the Orion Crew Exploration Vehicle (CEV) aides in getting the crew safely away from a failed Crew Launch Vehicle (CLV). Unlike the passive nature of the Apollo system, the Orion Launch Abort Vehicle will be actively controlled, giving the program a more robust abort system with a higher probability of crew survival for an abort at all points throughout the CLV trajectory. By optimizing the concept of operations and thrust profile the Orion program will be able to take full advantage of the active Orion LAS. Discussion will involve an overview of the development of the abort motor thrust profile and the current abort concept of operations as well as their effects on the performance of LAS aborts. Pad Abort (for performance) and Maximum Drag (for separation from the Launch Vehicle) are the two points that dictate the required thrust and shape of the thrust profile. The results in this paper show that 95% success of all performance requirements is not currently met for Pad Abort. Future improvements to the current parachute sequence and other potential changes will mitigate the current problems, and meet abort performance requirements

Mining unexpected temporal associations: Applications in detecting adverse drug reactions

Copyright © 2008 IEEEIn various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. TheMUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.Huidong (Warren) Jin, Jie Chen, Member, Hongxing He, Graham J. Williams, Chris Kelman and Christine M. O’Keef

Twelve tips for structuring student placements to achieve interprofessional learning outcomes

Published: 19/10/2016Background: Increasingly, universities are being asked to provide evidence of interprofessional learning within their health and human services programs. Given the authentic nature of the placement setting, this component of curricula is well suited to provide students with these interprofessional learning experiences. Aims: To describe twelve tips for structuring student placements to achieve interprofessional learning outcomes. Methods: Development of these 12 tips was based on knowledge and experience drawn from the literature, focus groups and workshop with experts within the field, together with the authors’ own experiences over many years of teaching in multidisciplinary and interprofessional contexts. Results and conclusions: The tips provide direction and clarity for universities and placement sites to facilitate authentic learning in practice based settings. In particular, they describe the ways in which placements can be structured to maximise opportunities for students to achieve specific interprofessional competencies. They are underpinned by the principle that interprofessional learning should be a core component of all healthcare placements and that student learning occurs through participation in routine work activity in addition to structured learning activities.Gillian Nisbet, Maree O'Keefe, Amanda Henderso

DNA Methylation of the ABO Promoter Underlies Loss of ABO Allelic Expression in a Significant Proportion of Leukemic Patients

Background: Loss of A, B and H antigens from the red blood cells of patients with myeloid malignancies is a frequent occurrence. Previously, we have reported alterations in ABH antigens on the red blood cells of 55% of patients with myeloid malignancies. Methodology/Principal Findings: To determine the underlying molecular mechanisms of this loss, we assessed ABO allelic expression in 21 patients with ABH antigen loss previously identified by flow cytometric analysis as well as an additional 7 patients detected with ABH antigen changes by serology. When assessing ABO mRNA allelic expression, 6/12 (50%) patients with ABH antigen loss detected by flow cytometry and 5/7 (71%) of the patients with ABH antigen loss detected by serology had a corresponding ABO mRNA allelic loss of expression. We examined the ABO locus for copy number and DNA methylation alterations in 21 patients, 11 with loss of expression of one or both ABO alleles, and 10 patients with no detectable allelic loss of ABO mRNA expression. No loss of heterozygosity (LOH) at the ABO locus was observed in these patients. However in 8/11 (73%) patients with loss of ABO allelic expression, the ABO promoter was methylated compared with 2/10 (20%) of patients with no ABO allelic expression loss (P = 0.03). Conclusions/Significance: We have found that loss of ABH antigens in patients with hematological malignancies is associated with a corresponding loss of ABO allelic expression in a significant proportion of patients. Loss of ABO allelic expression was strongly associated with DNA methylation of the ABO promoter.Tina Bianco-Miotto, Damian J. Hussey, Tanya K. Day, Denise S. O'Keefe and Alexander Dobrovi

Intermediate statistics in quantum maps

We present a one-parameter family of quantum maps whose spectral statistics are of the same intermediate type as observed in polygonal quantum billiards. Our central result is the evaluation of the spectral two-point correlation form factor at small argument, which in turn yields the asymptotic level compressibility for macroscopic correlation lengths

BMP-2 induces ATF4 phosphorylation in chondrocytes through a COX-2/PGE2 dependent signaling pathway

SummaryObjectiveBone morphogenic protein (BMP)-2 is approved for fracture non-union and spine fusion. We aimed to further dissect its downstream signaling events in chondrocytes with the ultimate goal to develop novel therapeutics that can mimic BMP-2 effect but have less complications.MethodsBMP-2 effect on cyclooxygenase (COX)-2 expression was examined using Real time quantitative PCR (RT-PCR) and Western blot analysis. Genetic approach was used to identify the signaling pathway mediating the BMP-2 effect. Similarly, the pathway transducing the PGE2 effect on ATF4 was investigated. Immunoprecipitation (IP) was performed to assess the complex formation after PGE2 binding.ResultsBMP-2 increased COX-2 expression in primary mouse costosternal chondrocytes (PMCSC). The results from the C9 Tet-off system demonstrated that endogenous BMP-2 also upregulated COX-2 expression. Genetic approaches using PMCSC from ALK2fx/fx, ALK3fx/fx, ALK6−/−, and Smad1fx/fx mice established that BMP-2 regulated COX-2 through activation of ALK3–Smad1 signaling. PGE-2 EIA showed that BMP-2 increased PGE2 production in PMCSC. ATF4 is a transcription factor that regulates bone formation. While PGE2 did not have significant effect on ATF4 expression, it induced ATF4 phosphorylation. In addition to stimulating COX-2 expression, BMP-2 also induced phosphorylation of ATF4. Using COX-2 deficient chondrocytes, we demonstrated that the BMP-2 effect on ATF4 was COX-2-dependent. Tibial fracture samples from COX-2−/− mice showed reduced phospho-ATF4 immunoreactivity compared to wild type (WT) ones. PGE2 mediated ATF4 phosphorylation involved signaling primarily through the EP2 and EP4 receptors and PGE2 induced an EP4-ERK1/2-RSK2 complex formation.ConclusionsBMP-2 regulates COX-2 expression through ALK3–Smad1 signaling, and PGE2 induces ATF4 phosphorylation via EP4-ERK1/2-RSK2 axis

The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds

The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds

A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families

HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females

Event-based camera refractory period characterization and initial clock drift evaluation

Event-based camera (EBC) technology provides high-dynamic range operation and shows promise for efficient capture of spatio-temporal information, producing a sparse data stream and enabling consideration of nontraditional data processing solutions (e.g., new algorithms, neuromorphic processors, etc.). Given the fundamental difference in camera architecture, the EBC response and noise behavior differ considerably compared to standard CCD/CMOS framing sensors. These differences necessitate the development of new characterization techniques and sensor models to evaluate hardware performance and elucidate the trade-space between the two camera architectures. Laboratory characterization techniques reported previously include noise level as a function of static scene light level (background activity) and contrast responses referred to as S-curves. Here we present further progress on development of basic characterization methods and test capabilities for commercial-off-the-shelf (COTS) visible EBCs, with a focus on measurement of pixel deadtime (refractory period) including results for the 4th-generation sensor from Prophesee and Sony. Refractory period is empirically determined from analysis of the interspike intervals (ISIs), and results visualized using log-histograms of the minimum per-pixel ISI values for a subset of pixels activated by a controlled dynamic scene. Our tests of the Prophesee gen4 EVKv2 yield refractory period estimates ranging from 6.1 msec to 6.8 μsec going from the slowest (20) to fastest (100) settings of the relevant bias parameter, bias_refr. We also introduce and demonstrate the concept of pixel bandwidth measurement from data captured while viewing a static scene – based on recording data at a range of refractory period setting and then analyzing noise-event statistics. Finally, we present initial results for estimating and correcting EBC clock drift using a GPS PPS signal to generate special timing events in the event-list data streams generated by the DAVIS346 and DVXplorer EBCs from iniVation