2,497 publications from this institution
Performance is an important aspect of integrated circuit design, and depends in part on the speed of the underlying circuits. This thesis presents a new method of analyzing MOS circuit delay, based on a single-time-constant approximation. The timing models characterize the circuit by a single parameter, which depends on the resistance and capacitance of the circuit elements. To ensure the single- time-constant approximation is valid for a particular circuit, the timing models provide both an estimate and bounds for the output waveform. For circuits where the bounds are poor, an improved timing model is derived. These simple models provide insight about circuit performance issues, as well as determining the circuit delay. The timing models are first developed for linear networks and then are extended to model MOS circuits driven by a step input. By using the single-time-constant approximation, the output waveform of a complex MOS circuit can be modelled by the output of a circuit consisting of a single MOS transistor and a single capacitor. Finally, a new circuit model of a gate is used to derive the output waveform of a circuit driven by an arbitrary input. The resulting timing model does not depend strongly on the shape of the input: the output waveform only depends on the input''s slope at the gate''s switching voltage.
Abstract Amino acids in variable positions of proteins may be correlated, with potential structural and functional implications. Here, we apply exact tests of independence in R × C contingency tables to examine noise-free associations between variable positions of the SARS-CoV-2 spike protein, using as a paradigm sequences from Greece deposited in GISAID (N=6,683/1,078 full-length) for the period February 29, 2020 to April 26, 2021 that essentially covers the first three pandemic waves. We examine the fate and complexity of these associations by network analysis, using associated positions (exact p≤0.001 and Average Product Correction ≥2) as links and the corresponding positions as nodes . We found a temporal linear increase of positional differences and a gradual expansion of the number of position associations over time, represented by a temporally evolving intricate web, resulting in a non-random complex network of 69 nodes and 252 links. Overconnected nodes corresponded to the most adapted variant positions in the population, suggesting a direct relation between network degree and position functional importance. Modular analysis revealed 25 k -cliques comprising three to 11 nodes. At different k - clique resolutions, one to four communities were formed, capturing epistatic associations of circulating variants (Alpha, Beta, B.1.1.318), but also Delta, which dominated the evolutionary landscape later in the pandemic. Cliques of aminoacidic positional associations tended to occur in single sequences, enabling the recognition of epistatic positions in real-world virus populations. Our findings provide a novel way of understanding epistatic relationships in viral proteins with potential applications in the design of virus control procedures. Importance Paired positional associations of adapted amino acids in virus proteins may provide new insights for understanding virus evolution and variant formation. We investigated potential intramolecular relationships between variable SARS-CoV-2 spike positions by exact tests of independence in R × C contingency tables, having applied Average Product Correction (APC) to eliminate background noise. Associated positions (exact p≤0.001 and APC≥2) formed a non- random, epistatic network of 25 cliques and 1-4 communities at different clique resolutions, revealing evolutionary ties between variable positions of circulating variants, and a predictive potential of previously unknown network positions. Cliques of different sizes represented theoretical combinations of changing residues in sequence space, allowing the identification of significant aminoacidic combinations in single sequences of real-world populations. Our analytic approach that links network structural aspects to mutational aminoacidic combinations in the spike sequence population offers a novel way to understand virus epidemiology and evolution.
John Ioannidis has been editor-in-chief of the European Journal of Clinical Investigation and a member of the editorial board of the Journal of Clinical Epidemiology and of PLoS Medicine, has published papers in these journals as well as in Nature, Science, NEJM, JAMA and BMJ and recently was invited to contribute also to European Heart Journal. Brett Thombs has published papers in JAMA and BMJ. Both authors have published numerous articles, reviews, editorials and guidelines. The perspective expresses the views of the authors and not of any journals, societies or institutions where they may serve.
ABSTRACT Journalistic papers published in high impact journals can be very influential, especially in hot fields. This meta-research analysis aimed to evaluate the publication profiles, impact, and disclosures of conflicts of interest of non-research authors who had published >200 Scopus-indexed papers in Nature, Science, PNAS, Cell, BMJ, Lancet, JAMA or New England Journal of Medicine. 154 prolific authors were identified, 148 of whom had published 67,825 papers in their main affiliated journal in a non-researcher capacity. Of 25 massively prolific authors with over 700 publications in one of these journals, only 3 had a PhD degree in any subject matter. Only 2 of the 25 disclosed potential conflicts with some specificity. The practice of assigning so much power to non-researchers in shaping scientific discourse should be further debated and disclosures of potential conflicts of interest should be emphasized.
James A. Diao, BS; Gloria J. Wu, BS; Herman A. Taylor, MD; John K. Tucker, MD; Neil R. Powe, MD, MPH, MBA; Isaac S. Kohane, MD, PhD; Arjun K. Manrai, PhD
Abstract Cardiovascular disease and diabetes are intricately related and influenced by factors within the “exposome”. The exposome refers to a broad assessment of cumulative environmental exposures, including physical-chemical, biological, behavior, ecosystem, and social influences, experienced from conception throughout life, along with their dynamic interactions with the genome (Vermeulen et al. 2020). Distinguishing between correlational and potentially causative risk associations is challenging, especially at exposome scale. Here, we triangulate observational Exposome-Wide Association Study ( ExWAS ) evidence with “randomized” evidence for the exposome using mendelian randomization (MR) for almost 500 exposures. First, the ExWAS identified 144 significant factors for coronary artery disease (CAD) and 237 for type 2 diabetes (T2D), with 120 shared between both. These factors had modest predictive ability (variance explained) for both phenotypes. However, a genetic-based potentially causative relationship was deduced for only 14 factors in CAD and 16 in T2D, with seven implicated in both. Additionally, we found strong concordance of MR-validated findings between prevalent and incident disease associations (85.7% [12/14] for CAD and 87.5% [14/16] for T2D). Most correlational findings pertain to lifestyle factors (particularly diet), but social educational factors are more prominently highlighted among those with potentially causative support.
Background: The objective of this study was to determine the presence of a set of prespecified criteria used to assess scientists for promotion and tenure within faculties of medicine among the U15 Group of Canadian Research Universities. Methods: Each faculty guideline for assessing promotion and tenure was reviewed and the presence of five traditional (peer-reviewed publications, authorship order, journal impact factor, grant funding, and national/international reputation) and seven nontraditional (citations, data sharing, publishing in open access mediums, accommodating leaves, alternative ways for sharing research, registering research, using reporting guidelines) criteria were collected by two reviewers. Results: Among the U15 institutions, four of five traditional criteria (80.0%) were present in at least one promotion guideline, whereas only three of seven nontraditional incentives (42.9%) were present in any promotion guidelines. When assessing full professors, there were a median of three traditional criteria listed, versus one nontraditional criterion. Conclusion: This study demonstrates that faculties of medicine among the U15 Group of Canadian Research Universities base assessments for promotion and tenure on traditional criteria. Some of these metrics may reinforce problematic practices in medical research. These faculties should consider incentivizing criteria that can enhance the quality of medical research.
This paper describes the construction and analysis of several diagrams which depict SRT division algorithms. These diagrams yield insight into the operation of the algorithms and the many implementation tradeoffs available in custom circuit design. Examples of simple low radix diagrams are shown, as well as tables for higher radices. The tables were generated by a program which can create and verify the diagrams for different division schemes. Also discussed is a custom CMOS integrated circuit designed which performs SRT division using self-timed circuit techniques. This chip implements an intermediate approach between a fully combinational array and a fully iterative in time method in order to get both speed and small silicon area.
