A failure recovery planning prototype for Space Station Freedom

NASA is investigating the use of advanced automation to enhance crew productivity for Space Station Freedom in numerous areas, including failure management. A prototype is described that uses various advanced automation techniques to generate courses of action whose intents are to recover from a diagnosed failure, and to do so within the constraints levied by the failure and by Freedom's configuration and operating conditions

The Relationship Between Prior Experiences in Mathematics and Pharmacy School Success

Objective. To assess students’ pre-pharmacy math experiences, confidence in math ability, and relationship between experiences, confidence, and grades in math-based pharmacy courses. Methods. A cross-sectional survey of first year to third year pharmacy students was conducted. Students reported type of pre-pharmacy math courses taken, when they were taken [high school (HS) vs. college] and year of HS and college graduation. Students rated their confidence in math ability using the previously validated 11-item Fogerty Math Confidence Scale (Cronbach alpha=0.92). Math grade point average (GPA), Pharmacy College Admission Test quantitative (PCAT quant) scores, and grades (calculations and kinetics) were obtained from transcripts and school records. Spearman correlation and multivariate linear regression were used to compare math experiences, confidence, and grades. Results. There were 198 students who reported taking math courses 7.1 years since HS graduation and 2.9 years since their last schooling prior to pharmacy school. Students who took math courses with more time since HS/last schooling had lower calculations and kinetics grades. Students reporting having taken more HS math courses had better calculations grades. Students with higher math GPA, and PCAT quant scores also had higher calculations and kinetics grades. Greater confidence in math ability was associated with higher calculations grades. In multivariate regressions, PCAT quant scores and years since HS independently predicted calculations grades, and PCAT quant scores independently predicted kinetics grades. Conclusion. The number of pre-pharmacy math courses and time elapsed since they were taken are important factors to consider when predicting a pharmacy student’s success in math-based pharmacy school courses

Quantitative analysis of ruminal methanogenic microbial populations in beef cattle divergent in phenotypic residual feed intake (RFI) offered contrasting diets

peer-reviewedBackground Methane (CH4) emissions in cattle are an undesirable end product of rumen methanogenic fermentative activity as they are associated not only with negative environmental impacts but also with reduced host feed efficiency. The aim of this study was to quantify total and specific rumen microbial methanogenic populations in beef cattle divergently selected for residual feed intake (RFI) while offered (i) a low energy high forage (HF) diet followed by (ii) a high energy low forage (LF) diet. Ruminal fluid was collected from 14 high (H) and 14 low (L) RFI animals across both dietary periods. Quantitative real time PCR (qRT-PCR) analysis was conducted to quantify the abundance of total and specific rumen methanogenic microbes. Spearman correlation analysis was used to investigate the association between the relative abundance of methanogens and animal performance, rumen fermentation variables and diet digestibility. Results Abundance of methanogens, did not differ between RFI phenotypes. However, relative abundance of total and specific methanogen species was affected (P < 0.05) by diet type, with greater abundance observed while animals were offered the LF compared to the HF diet. Conclusions These findings suggest that differences in abundance of specific rumen methanogen species may not contribute to variation in CH4 emissions between efficient and inefficient animals, however dietary manipulation can influence the abundance of total and specific methanogen species.Funding for the development and main work of this research was provided under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Fisheries & Food, Ireland RSF 05 224

Ergodicity and Accuracy of Optimal Particle Filters for Bayesian Data Assimilation

Data assimilation refers to the methodology of combining dynamical models and observed data with the objective of improving state estimation. Most data assimilation algorithms are viewed as approximations of the Bayesian posterior (filtering distribution) on the signal given the observations. Some of these approximations are controlled, such as particle filters which may be refined to produce the true filtering distribution in the large particle number limit, and some are uncontrolled, such as ensemble Kalman filter methods which do not recover the true filtering distribution in the large ensemble limit. Other data assimilation algorithms, such as cycled 3DVAR methods, may be thought of as controlled estimators of the state, in the small observational noise scenario, but are also uncontrolled in general in relation to the true filtering distribution. For particle filters and ensemble Kalman filters it is of practical importance to understand how and why data assimilation methods can be effective when used with a fixed small number of particles, since for many large-scale applications it is not practical to deploy algorithms close to the large particle limit asymptotic. In this paper, the authors address this question for particle filters and, in particular, study their accuracy (in the small noise limit) and ergodicity (for noisy signal and observation) without appealing to the large particle number limit. The authors first overview the accuracy and minorization properties for the true filtering distribution, working in the setting of conditional Gaussianity for the dynamics-observation model. They then show that these properties are inherited by optimal particle filters for any fixed number of particles, and use the minorization to establish ergodicity of the filters. For completeness we also prove large particle number consistency results for the optimal particle filters, by writing the update equations for the underlying distributions as recursions. In addition to looking at the optimal particle filter with standard resampling, they derive all the above results for (what they term) the Gaussianized optimal particle filter and show that the theoretical properties are favorable for this method, when compared to the standard optimal particle filter

The search for novel analgesics: re-examining spinal cord circuits with new tools

In this perspective, we propose the absence of detailed information regarding spinal cord circuits that process sensory information remains a major barrier to advancing analgesia. We highlight recent advances showing that functionally discrete populations of neurons in the spinal cord dorsal horn play distinct roles in processing sensory information. We then discuss new molecular, electrophysiological, and optogenetic techniques that can be employed to understand how dorsal horn circuits process tactile and nociceptive information. We believe this information can drive the development of entirely new classes of pharmacotherapies that target key elements in spinal circuits to selectively modify sensory function and blunt pain

A novel human glucocorticoid receptor SNP results in increased transactivation potential.

Glucocorticoids are one of the most widely used therapeutics in the treatment of a variety of inflammatory disorders. However, it is known that there are variable patient responses to glucocorticoid treatment; there are responders and non-responders, or those that need higher dosages. Polymorphisms in the glucocorticoid receptor (GR) have been implicated in this variability. In this study, ninety-seven volunteers were surveyed for polymorphisms in the human GR-alpha (hGRα), the accepted biologically active reference isoform. One isoform identified in our survey, named hGR DL-2, had four single nucleotide polymorphisms (SNPs), one synonymous and three non-synonymous, and a four base pair deletion resulting in a frame shift and early termination to produce a 743 amino acid putative protein. hGR DL-2 had a decrease in transactivation potential of more than 90%. Upon further analysis of the individual SNPs and deletion, one SNP, A829G, which results in a lysine to glutamic acid amino acid change at position 277, was found to increase the transactivation potential of hGR more than eight times the full-length reference. Furthermore, the hGRα-A829G isoform had a differential hyperactive response to various exogenous steroids. Increasing our knowledge as to how various SNPs affect hGR activity may help in understanding the unpredictable patient response to steroid treatment, and is a step towards personalizing patient care

A failure management prototype: DR/Rx

This failure management prototype performs failure diagnosis and recovery management of hierarchical, distributed systems. The prototype, which evolved from a series of previous prototypes following a spiral model for development, focuses on two functions: (1) the diagnostic reasoner (DR) performs integrated failure diagnosis in distributed systems; and (2) the recovery expert (Rx) develops plans to recover from the failure. Issues related to expert system prototype design and the previous history of this prototype are discussed. The architecture of the current prototype is described in terms of the knowledge representation and functionality of its components

MV-22B LOGISTICS FLIGHTS SUSTAINING THE AVIATION COMBAT ELEMENT IN THE INDO-PACIFIC

This research analyzes the usage of the MV-22B for logistics or passenger/mail/cargo sorties in the Indo-Pacific region. Specifically, it focuses on its application to the transport of high-priority aircraft parts from locations ashore to the aviation combat element embarked on an amphibious assault ship, multipurpose (LHD) or amphibious assault ship, general purpose (LHA). Supporting the aviation combat element as it conducts distributed aviation operations inside and on the periphery of the weapon engagement zone in the Pacific is widely unknown in an expeditionary advanced base framework in the great power competition. Two hypothetical scenarios are presented as frameworks to aid in the understanding of MV-22B utilization for logistics. Real-world high-priority aircraft part demand and sortie data, provided by the operating forces, were collected, analyzed, and inserted into the scenarios. The resulting outputs provide new insight on aircraft employment and risks associated with sorties in the engagement zone. Recommendations are given for improving sustainment capabilities while operating in a Marine expeditionary unit construct.Captain, United States Marine CorpsMajor, United States Marine CorpsApproved for public release. Distribution is unlimited

Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia

Nelarabine is the prodrug of 9-β-arabinofuranosylguanine (ara-G) and is therapeutically classified as a purine nucleoside analog. Nelarabine is converted to ara-G by adenosine deaminase and transported into cells by a nucleoside transporter. Ara-G is subsequently phosphorylated to ara-G triphosphate (ara-GTP), thereby initiating the therapeutic effect by inhibiting DNA synthesis. Nelarabine has been extensively studied in regards to its pharmacokinetics, and the data have demonstrated that ara-GTP preferentially accumulates in malignant T-cells. Clinical responses to nelarabine have been demonstrated in various T-cell malignancies and appear to correlate with a relatively high intracellular concentration of ara-GTP compared to nonresponders. Therefore, this unique drug feature of nelarabine accounts for clinical utilization in treating adult and pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Neuropathy is the most predominant adverse effect associated with nelarabine and the incidence correlates with the dose administered. Myelosuppression has been observed, with thrombocytopenia and neutropenia as the most common hematologic complications. This article reviews the pharmacology, mechanism of action, and pharmacokinetic properties of nelarabine, as well as nelarabine’s clinical efficacy in T-ALL, T-LBL, and other hematologic malignancies. The toxicity profile, dosage, and administration, and areas of ongoing and future research, are also presented