An application generator for rapid prototyping of Ada real-time control software

The need to increase engineering productivity and decrease software life cycle costs in real-time system development establishes a motivation for a method of rapid prototyping. The design by iterative rapid prototyping technique is described. A tool which facilitates such a design methodology for the generation of embedded control software is described

RT_BUILD: An expert programmer for implementing and simulating Ada real-time control software

The RT BUILD is an expert control system programmer that creates real-time Ada code from block-diagram descriptions of control systems. Since RT BUILD embodies substantial knowledge about the implementation of real-time control systems, it can perform many, if not most of the functions normally performed by human real-time programmers. Though much basic research was done in automatic programming, RT BUILD appears to be the first application of this research to an important problem in flight control system development. In particular, RT BUILD was designed to directly increase productivity and reliability for control implementations of large complex systems

Avalanches on a conical bead pile: scaling with tuning parameters

Uniform spherical beads were used to explore the behavior of a granular system near its critical angle of repose on a conical bead pile. We found two tuning parameters that could take the system to a critical point where a simple power-law described the avalanche size distribution as predicted by self-organized criticality, which proposed that complex dynamical systems self-organize to a critical point without need for tuning. Our distributions were well described by a simple power-law with the power {\tau} = 1.5 when dropping beads slowly onto the apex of a bead pile from a small height. However, we could also move the system from the critical point using either of two tuning parameters: the height from which the beads fell onto the top of the pile or the region over which the beads struck the pile. As the drop height increased, the system did not reach the critical point yet the resulting distributions were independent of the bead mass, coefficient of friction, or coefficient of restitution. All our apex-dropping distributions for any type of bead (glass, stainless steel, zirconium) showed universality by scaling onto a common curve with {\tau} = 1.5 and {\sigma} = 1.0, where 1/{\sigma} is the power of the tuning parameter. From independent calculations using the moments of the distribution, we find values for {\tau} = 1.6 \pm 0.1 and {\sigma} = 0.91 \pm 0.15. When beads were dropped across the surface of the pile instead of solely on the apex, then the system also moved from the critical point and again the avalanche size distributions fell on a common curve when scaled similarly using the same values of {\tau} and {\sigma}. We also observed that an hcp structure on the base of the pile caused an emergent structure in the pile that had six faces with some fcc or hcp structure.Comment: 8 pages, 6 figures; submitted to Granular Matter; Reformatted into LaTeX from Word; Fixed typo in uncertainty of tau; Rearranged two paragraphs to improve flo

An Empirical Comparison of the Anova F-Test, Normal Scores Test and Kruskal-Wallis Test Under Violation of Assumptions

The present research compares the ANOVA F-test, the Kruskal-Wallis test, and the normal scores test in terms of empirical alpha and empirical power with samples from the normal distribution and two exponential distributions. Empirical evidence supports the use of the ANOVA F-test even under violation of assumptions when testing hypotheses about means. If the researcher is willing to test hypotheses about medians, the Kruskal-Wallis test was found to be competitive to the F-test. However, in the cases investigated, the normal scores test was not consistently better than the F-test or the Kruskal-Wallis test and could not be recommended on the basis of this research.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

<p>Abstract</p> <p>Background</p> <p>Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid) injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal). These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability.</p> <p>Methods</p> <p>In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively) or placebo (NCT#00590577). Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS) score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity) using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE) rates and relative risks (RR) with 95% confidence intervals (CI) versus placebo were determined.</p> <p>Results</p> <p>Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS) mean PANSS total score at Day 8 (p = 0.037). After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo) and Day 36 (p < 0.001). Taken together with results in the 39 mg and 234 mg Day 8 arms, these findings suggest a trend towards a dose-dependent response. During Days 1 to 7, AEs reported in ≥2% of paliperidone palmitate subjects (234 mg) and a greater proportion of paliperidone palmitate than placebo subjects were: agitation (3.2% vs. 1.3%; RR 2.52 [95% CI 0.583, 10.904]), headache (4.0% vs. 3.8%; RR 1.06 [95% CI 0.433, 2.619]), and injection site pain (6.7% vs. 3.8%; RR 1.79 [95% CI 0.764, 4.208]). Days 8 to 36 AEs meeting the same criteria in the 156 mg Day 8 arm were: anxiety (3.1% vs. 2.5%; RR 1.24 [95% CI 0.340, 4.542]), psychotic disorder (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), dizziness (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), and injection site pain (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]). Corresponding Days 8 to 36 AEs in the 39 mg Day 8 group were: agitation (4.5% vs. 4.4%; RR 1.03 [95% CI 0.371, 2.874]), anxiety (3.9% vs. 2.5%; RR 1.55 [95% CI 0.446, 5.381]), and psychotic disorder (2.6% vs. 1.3%; RR 2.07 [95% CI 0.384, 11.110]) while in the 234 mg Day 8 group it was anxiety (3.1% vs. 2.5%, RR 1.25 [95% CI 0.342, 4.570]).</p> <p>Conclusions</p> <p>Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1) compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose-dependent response. No unexpected tolerability findings were noted in the first week or month after the initiation dosing.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT#00590577">NCT#00590577</a></p

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to&nbsp;RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead