On-orbit structural dynamic performance of a 15-meter microwave radiometer antenna

The on-orbit structural dynamic performance of a microwave radiometer antenna for Earth science applications is addressed. The radiometer is one of the Earth-observing instruments aboard a proposed geostationary platform as part of the Mission to the Planet Earth. A sequential approach is presented for assessing the ability of an antenna structure to retain its geometric shape subject to a representative onboard disturbance. This approach includes establishing the structural requirements of the antenna, developing the structural and disturbance models, performing modal and forced response analyses, and evaluating the resulting distortions in terms of the antenna's ability to meet stringent structural performance requirements. Two antenna configurations are discussed: free-flying and platform-mounted. These configurations are analyzed for a representative disturbance function which simulates rotation of the subreflector in order to perform a raster-type scan of the Earth disk. Results show that the scanning maneuver modeled would not induce antenna structural errors outside the specified limits

Executing Formal Specifications with Constraint Programming

We have implemented a technique for execution of formal, model-based specifications. The specifications we can execute are written at a level of abstraction that has not previously been supported in executable specification languages. The specification abstractions supported by our execution technique include quantified assertions that reference post-state values, and indirect definitions of post-state values (definitions that do not use equality). Our approach is based on translating specifications to the concurrent constraint programming language AKL. While there are, of course, expressible assertions that are not executable, our technique is amenable to any formal specification language based on a finite number of intrinsic types and pre- and postcondition assertions

The Direct Execution of SPECS-C++: A Model-Based Specification Language for C++ Classes

Executable specification languages may be the key to more widespread use of formal methods in software production. However, the expressiveness of executable specification languages is typically much less than that of non-executable specification languages such as VDM or Z. Thus, specifiers are forced to work at a lower level of abstraction to gain the advantage of executability. Additionally, specifications are typically made executable by translating them to a programming language, so errors in the specification can only be detected as errors in the resulting code. This paper presents a technique for directly executing specifications written in SPECS-C++, a model-based specification language for C++ classes. As SPECS-C++ has much in common with the implicit subset of VDM, this technique is equally applicable to implicit VDM specifications. Standard ML code for the interpreter and the example used in the paper appear in the appendices

Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report

Neuromuscular electrical stimulation has been used to aid musculoskeletal recovery. Excessive oxidative stress and excitoxicity are implicated in secondary progressive multiple sclerosis. A 52-year-old white female with SPMS had been scooter- and cane-dependent for 4 years. She requested and received a trial of neuromuscular electrical stimulation. Two months after initiating NMES the patient adopted several nutritional interventions to lower oxidative stress and excito-toxicity. During the first 2 months of neuromuscular electrical stimulation, the therapist observed modest gait improvements. Following the addition of nutritional interventions, more rapids gains in strength and endurance, including muscle groups not receiving neuromuscular electrical stimulation were observed by both the therapist and the patient. After 8 months of neuromuscular electrical stimulation (6 months of nutritional intervention) the patient’s function had improved sufficiently that she no longer used a scooter or cane and rode her bicycle routinely 8 miles, including hills

The frequency of missed test results and associated treatment delays in a highly computerized health system

<p>Abstract</p> <p>Background:</p> <p>Diagnostic errors associated with the failure to follow up on abnormal diagnostic studies ("missed results") are a potential cause of treatment delay and a threat to patient safety. Few data exist concerning the frequency of missed results and associated treatment delays within the Veterans Health Administration (VA).</p> <p>Objective:</p> <p>The primary objective of the current study was to assess the frequency of missed results and resulting treatment delays encountered by primary care providers in VA clinics.</p> <p>Methods:</p> <p>An anonymous on-line survey of primary care providers was conducted as part of the health systems ongoing quality improvement programs. We collected information from providers concerning their clinical effort (e.g., number of clinic sessions, number of patient visits per session), number of patients with missed abnormal test results, and the number and types of treatment delays providers encountered during the two week period prior to administration of our survey.</p> <p>Results:</p> <p>The survey was completed by 106 out of 198 providers (54 percent response rate). Respondents saw and average of 86 patients per 2 week period. Providers encountered 64 patients with missed results during the two week period leading up to the study and 52 patients with treatment delays. The most common missed results included imaging studies (29 percent), clinical laboratory (22 percent), anatomic pathology (9 percent), and other (40 percent). The most common diagnostic delays were cancer (34 percent), endocrine problems (26 percent), cardiac problems (16 percent), and others (24 percent).</p> <p>Conclusion:</p> <p>Missed results leading to clinically important treatment delays are an important and likely underappreciated source of diagnostic error.</p

Patient- and system-related barriers for the earlier diagnosis of colorectal cancer

<p>Abstract</p> <p>Background</p> <p>A cohort of colorectal cancer (CRC) patients represents an opportunity to study missed opportunities for earlier diagnosis. Primary objective: To study the epidemiology of diagnostic delays and failures to offer/complete CRC screening. Secondary objective: To identify system- and patient-related factors that may contribute to diagnostic delays or failures to offer/complete CRC screening.</p> <p>Methods</p> <p>Setting: Rural Veterans Administration (VA) Healthcare system. Participants: CRC cases diagnosed within the VA between 1/1/2000 and 3/1/2007. Data sources: progress notes, orders, and pathology, laboratory, and imaging results obtained between 1/1/1995 and 12/31/2007. Completed CRC screening was defined as a fecal occult blood test or flexible sigmoidoscopy (both within five years), or colonoscopy (within 10 years); delayed diagnosis was defined as a gap of more than six months between an abnormal test result and evidence of clinician response. A summary abstract of the antecedent clinical care for each patient was created by a certified gastroenterologist (GI), who jointly reviewed and coded the abstracts with a general internist (TW).</p> <p>Results</p> <p>The study population consisted of 150 CRC cases that met the inclusion criteria. The mean age was 69.04 (range 35-91); 99 (66%) were diagnosed due to symptoms; 61 cases (46%) had delays associated with system factors; of them, 57 (38% of the total) had delayed responses to abnormal findings. Fifteen of the cases (10%) had prompt symptom evaluations but received no CRC screening; no patient factors were identified as potentially contributing to the failure to screen/offer to screen. In total, 97 (65%) of the cases had missed opportunities for early diagnosis and 57 (38%) had patient factors that likely contributed to the diagnostic delay or apparent failure to screen/offer to screen.</p> <p>Conclusion</p> <p>Missed opportunities for earlier CRC diagnosis were frequent. Additional studies of clinical data management, focusing on following up abnormal findings, and offering/completing CRC screening, are needed.</p

Phosphorylation-Independent Regulation of Atf1-Promoted Meiotic Recombination by Stress-Activated, p38 Kinase Spc1 of Fission Yeast

BACKGROUND:Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. METHODOLOGY/PRINCIPAL FINDINGS:We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. CONCLUSIONS/SIGNIFICANCE:The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1

Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes

Analysis of laser radiation using the Nonlinear Fourier transform

Modern high-power lasers exhibit a rich diversity of nonlinear dynamics, often featuring nontrivial co-existence of linear dispersive waves and coherent structures. While the classical Fourier method adequately describes extended dispersive waves, the analysis of time-localised and/or non-stationary signals call for more nuanced approaches. Yet, mathematical methods that can be used for simultaneous characterisation of localized and extended fields are not yet well developed. Here, we demonstrate how the Nonlinear Fourier transform (NFT) based on the Zakharov-Shabat spectral problem can be applied as a signal processing tool for representation and analysis of coherent structures embedded into dispersive radiation. We use full-field, real-time experimental measurements of mode-locked pulses to compute the nonlinear pulse spectra. For the classification of lasing regimes, we present the concept of eigenvalue probability distributions. We present two field normalisation approaches, and show the NFT can yield an effective model of the laser radiation under appropriate signal normalisation conditions

Superhelical Duplex Destabilization and the Recombination Position Effect

The susceptibility to recombination of a plasmid inserted into a chromosome varies with its genomic position. This recombination position effect is known to correlate with the average G+C content of the flanking sequences. Here we propose that this effect could be mediated by changes in the susceptibility to superhelical duplex destabilization that would occur. We use standard nonparametric statistical tests, regression analysis and principal component analysis to identify statistically significant differences in the destabilization profiles calculated for the plasmid in different contexts, and correlate the results with their measured recombination rates. We show that the flanking sequences significantly affect the free energy of denaturation at specific sites interior to the plasmid. These changes correlate well with experimentally measured variations of the recombination rates within the plasmid. This correlation of recombination rate with superhelical destabilization properties of the inserted plasmid DNA is stronger than that with average G+C content of the flanking sequences. This model suggests a possible mechanism by which flanking sequence base composition, which is not itself a context-dependent attribute, can affect recombination rates at positions within the plasmid