Circuit design tool. User's manual, revision 2

The CAM chip design was produced in a UNIX software environment using a design tool that supports definition of digital electronic modules, composition of these modules into higher level circuits, and event-driven simulation of these circuits. Our design tool provides an interface whose goals include straightforward but flexible primitive module definition and circuit composition, efficient simulation, and a debugging environment that facilitates design verification and alteration. The tool provides a set of primitive modules which can be composed into higher level circuits. Each module is a C-language subroutine that uses a set of interface protocols understood by the design tool. Primitives can be altered simply by recoding their C-code image; in addition new primitives can be added allowing higher level circuits to be described in C-code rather than as a composition of primitive modules--this feature can greatly enhance the speed of simulation

Content addressable memory project

A parameterized version of the tree processor was designed and tested (by simulation). The leaf processor design is 90 percent complete. We expect to complete and test a combination of tree and leaf cell designs in the next period. Work is proceeding on algorithms for the computer aided manufacturing (CAM), and once the design is complete we will begin simulating algorithms for large problems. The following topics are covered: (1) the practical implementation of content addressable memory; (2) design of a LEAF cell for the Rutgers CAM architecture; (3) a circuit design tool user's manual; and (4) design and analysis of efficient hierarchical interconnection networks

Radio continuum observations of Class I protostellar disks in Taurus: constraining the greybody tail at centimetre wavelengths

We present deep 1.8 cm (16 GHz) radio continuum imaging of seven young stellar objects in the Taurus molecular cloud. These objects have previously been extensively studied in the sub-mm to NIR range and their SEDs modelled to provide reliable physical and geometrical parametres.We use this new data to constrain the properties of the long-wavelength tail of the greybody spectrum, which is expected to be dominated by emission from large dust grains in the protostellar disk. We find spectra consistent with the opacity indices expected for such a population, with an average opacity index of beta = 0.26+/-0.22 indicating grain growth within the disks. We use spectra fitted jointly to radio and sub-mm data to separate the contributions from thermal dust and radio emission at 1.8 cm and derive disk masses directly from the cm-wave dust contribution. We find that disk masses derived from these flux densities under assumptions consistent with the literature are systematically higher than those calculated from sub-mm data, and meet the criteria for giant planet formation in a number of cases.Comment: submitted MNRA

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia