Telephone multiline signaling using common signal pair

An operator can rapidly and automatically produce coded electrical signals by manipulating mechanical thumb wheel switches so as to instruct a service center to connect any number of telephone lines to the console thus enabling the operator to listen and/or talk over several lines simultaneously. The system includes an on-site console having several mechanically operated thumb wheel switches to which the desired lines to be connected can be dialed in. Electrical coded signals are fed to a number of banks of line AND gates representing units, tens and hundreds, a group of channel gates, and a command gate. These signals are gated out in a controlled manner to an encoder which generates tones that are transmitted over a single line to a communication service center

A membrane cytoskeleton from Dictyostelium discoideum. II. Integral proteins mediate the binding of plasma membranes to F-actin affinity beads

In novel, low-speed sedimentation assays, highly purified, sonicated Dictyostelium discoideum plasma membrane fragments bind to F-actin beads (fluorescein-labeled F-actin on antifluorescein IgG-Sephacryl S-1000 beads). Binding was found to be (a) specific, since beads containing bound fluorescein-labeled ovalbumin or beads without bound fluorescein-labeled protein do not bind membranes, (b) saturable at approximately 0.6 microgram of membrane protein per microgram of bead-bound F-actin, (c) rapid with a t1/2 of 4-20 min, and (d) apparently of reasonable affinity since the off rate is too slow to be measured by present techniques. Using low-speed sedimentation assays, we found that sonicated plasma membrane fragments, after extraction with chaotropes, still bind F-actin beads. Heat-denatured membranes, proteolyzed membranes, and D. discoideum lipid vesicles did not bind F-actin beads. These results indicate that integral membrane proteins are responsible for the binding between sonicated membrane fragments and F-actin on beads. This finding agrees with the previous observation that integral proteins mediate interactions between D. discoideum plasma membranes and F-actin in solution (Luna, E.J., V. M. Fowler, J. Swanson, D. Branton, and D. L. Taylor, 1981, J. Cell Biol., 88:396-409). We conclude that low-speed sedimentation assays using F-actin beads are a reliable method for monitoring the associations between F-actin and membranes. Since these assays are relatively quantitative and require only micrograms of membranes and F-actin, they are a significant improvement over other existing techniques for exploring the biochemical details of F-actin-membrane interactions. Using F-actin beads as an affinity column for actin-binding proteins, we show that at least 12 integral polypeptides in D. discoideum plasma membranes bind to F-actin directly or indirectly. At least four of these polypeptides appear to span the membrane and are thus candidates for direct transmembrane links between the cytoskeleton and the cell surface

Investigating the relationship between mitochondrial genetic variation and cardiovascular-related traits to develop a framework for mitochondrial phenome-wide association studies

BACKGROUND: Mitochondria play a critical role in the cell and have DNA independent of the nuclear genome. There is much evidence that mitochondrial DNA (mtDNA) variation plays a role in human health and disease, however, this area of investigation has lagged behind research into the role of nuclear genetic variation on complex traits and phenotypic outcomes. Phenome-wide association studies (PheWAS) investigate the association between a wide range of traits and genetic variation. To date, this approach has not been used to investigate the relationship between mtDNA variants and phenotypic variation. Herein, we describe the development of a PheWAS framework for mtDNA variants (mt-PheWAS). Using the Metabochip custom genotyping array, nuclear and mitochondrial DNA variants were genotyped in 11,519 African Americans from the Vanderbilt University biorepository, BioVU. We employed both polygenic modeling and association testing with mitochondrial single nucleotide polymorphisms (mtSNPs) to explore the relationship between mtDNA variants and a group of eight cardiovascular-related traits obtained from de-identified electronic medical records within BioVU. RESULTS: Using polygenic modeling we found evidence for an effect of mtDNA variation on total cholesterol and type 2 diabetes (T2D). After performing comprehensive mitochondrial single SNP associations, we identified an increased number of single mtSNP associations with total cholesterol and T2D compared to the other phenotypes examined, which did not have more significantly associated SNPs than would be expected by chance. Among the mtSNPs significantly associated with T2D we identified variant mt16189, an association previously reported only in Asian and European-descent populations. CONCLUSIONS: Our replication of previous findings and identification of novel associations from this initial study suggest that our mt-PheWAS approach is robust for investigating the relationship between mitochondrial genetic variation and a range of phenotypes, providing a framework for future mt-PheWAS

A Formally Verified Floating-Point Implementation of the Compact Position Reporting Algorithm

The Automatic Dependent Surveillance-Broadcast (ADS-B) system allows aircraft to communicate their current state, including position and velocity information, to other aircraft in their vicinity and to ground stations. The Compact Position Reporting (CPR) algorithm is the ADS-B module responsible for the encoding and decoding of aircraft positions. CPR is highly sensitive to computer arithmetic since it heavily relies on functions that are intrinsically unstable such as floor and modulo. In this paper, a formally-verified double-precision floating-point implementation of the CPR algorithm is presented. The verification proceeds in three steps. First, an alternative version of CPR, which reduces the floating-point rounding error is proposed. Then, the Prototype Verification System (PVS) is used to formally prove that the ideal real-number counterpart of the improved algorithm is mathematically equivalent to the standard CPR definition. Finally, the static analyzer Frama-C is used to verify that the double-precision implementation of the improved algorithm is correct with respect to its operational requirement. The alternative algorithm is currently being considered for inclusion in the revised version of the ADS-B standards document as the reference implementation of the CPR algorithm

Defining and assessing spiritual health : a comparative study among 13- to 15-year-old pupils attending secular schools, Anglican schools, and private Christian schools in England and Wales

This article argues that the nation's commitment to young people involves proper concern for their physical health, their psychological health, and their spiritual health. In this context the notion of spiritual health is clarified by a critique of John Fisher's model of spiritual health. Fisher developed a relational model of spiritual health, which defines good spiritual health in terms of an individual's relationship to four domains: the personal, the communal, the environmental, and the transcendental. In the present analysis, we make comparisons between pupils educated in three types of schools: publicly funded schools without religious foundation, publicly funded schools with an Anglican foundation, and new independent Christian schools (not publicly funded). Our findings draw attention to significant differences in the levels of spiritual health experienced by pupils within these three types of schools

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions

Hi-MC: a novel method for high-throughput mitochondrial haplogroup classification

Effective approaches for assessing mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for mitochondrial haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for mitochondrial haplogroup classification that is cost effective and applicable to large sample sizes making mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American mitochondrial haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc