Reliable and Accountable System Design

Few would disagree with the assertion that safe engineering starts from the early stages of system design and should be maintained throughout the lifecycle. Different engineering domains have developed, mostly informal, frameworks with which they hope to promote this attitude. An interesting question for the KBS community is whether some of our methods for knowledge representation and reasoning can be used to assist in understanding, representing and interpreting such frameworks. This paper concentrates on what is (arguably) the area of greatest concern: relating system requirements to high level design. We highlight what appear to be the major difficulties which face us in this area, using examples from systems which have been built to tackle them.</jats:p

John C. Carapanayiotis (1909. – 1999.): grčki radiolog i pionir fizijatrije u Grčkoj

John C. Carapanayiotis was specialized in physical medicine and rehabilitation in the USA in 1948, at a time when the medical world in post-war Greece was ignorant of this specific medical specialty, and the political, economic and social backdrop was incapable of accepting and understanding the wealth of scientific knowledge that he was trying to introduce. At this point it should be noted that the specialty of Physical Medicine and Rehabilitation was established in Greece in 1973. John C. Carapanayiotis was a member of the American Congress of Physical Medicine during the 1950’s. In the same period, he expressed interest, on behalf of the New York University, in the establishment of a Physical Therapy Clinic in Greece, which would be granted unlimited funding by the Marshal Plan. His efforts clashed constantly with the backward mentality of his time, with the entrenched conservatism and with the bureaucratic red tape. Unfortunately, he was far ahead of his time and was condemned to the same fate as all other visionaries and pioneers in the way that his knowledge and scientific background were not put into practice for decades to come.John C. Carapanayiotis specijalizirao je fizikalnu medicine i rehabilitaciju 1948. u SAD-u, u vrijeme kada medicinski svijet u poslijeratnoj Grčkoj još nije bio upoznat s ovom specifičnom medicinskom specijalizacijom, a politička, ekonomska i društvena pozadina nije bila spremna prihvatiti bogatstvo znanstvenih spoznaja koje je pokušavao uvesti. Specijalizacija fizikalne medicine i rehabilitacije u Grčkoj je osnovana 1973. godine. John C. Carapanayiotis bio je član Američkog kongresa fizikalne medicine tijekom 1950-ih. U istom je razdoblju izrazio zainteresiranost, u ime Sveučilišta u New Yorku, za osnivanje Klinike za fizikalnu terapiju u Grčkoj, kojoj bi Marshallovim planom bilo odobreno neograničeno financiranje. Njegovi su se napori stalno sukobljavali s nazadnim mentalitetom njegova vremena, s ukorijenjenim konzervativizmom i birokracijom. Bio je daleko ispred svoga vremena, osuđen na sudbinu svih ostalih vizionara i pionira kojima se znanje i znanstvena pozadina nisu primjenjivali još desetljećima

Synthetic RNA Silencing of Actinorhodin Biosynthesis in Streptomyces coelicolor A3(2)

We demonstrate the first application of synthetic RNA gene silencers in Streptomyces coelicolor A3(2). Peptide nucleic acid and expressed antisense RNA silencers successfully inhibited actinorhodin production. Synthetic RNA silencing was target-specific and is a new tool for gene regulation and metabolic engineering studies in Streptomyces.Peer reviewe

Green Engineering Opportunities in the Pharmaceutical Industry

Discusses opportunities to integrate green engineering and pollution prevention practices into the pharmaceutical manufacturing process, most of which involve solvent reduction, substitution, and recovery.Ope

Transcriptomics and proteomics show that selenium affects inflammation, ctoskeleton, and cancer pathways in human rectal biopsies

Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk

Myosin VI facilitates connexin 43 gap junction accretion

In this study, we demonstrate myosin VI enrichment at Cx43 (also known as GJA1)-containing gap junctions (GJs) in heart tissue, primary cardiomyocytes and cell culture models. In primary cardiac tissue and in fibroblasts from the myosin VI-null mouse as well as in tissue culture cells transfected with siRNA against myosin VI, we observe reduced GJ plaque size with a concomitant reduction in intercellular communication, as shown by fluorescence recovery after photobleaching (FRAP) and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable for the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane. Furthermore, we cannot corroborate clathrin or Dab2 localization at gap junctions and we do not observe a function for the myosin-VI–Dab2 complex in clathrin-dependent endocytosis of annular gap junctions. Instead, we found that myosin VI was localized at the edge of Cx43 plaques by using total internal reflection fluorescence (TIRF) microscopy and use FRAP to identify a plaque accretion defect as the primary manifestation of myosin VI loss in Cx43 homeostasis. A fuller understanding of this derangement may explain the cardiomyopathy or gliosis associated with the loss of myosin VI.B.W. is a National Institutes of Health Oxford-Cambridge scholar supported by funding obtained by J.L.-S. from the Eunice Shriver National Institute of Child Health and Human Development. F.B. thanks the Wellcome Trust for funding of the Cambridge Institute for Medical Research (CIMR) Strategic Award (100140), an equipment grant (093026), the Medical Research Council (MR/K000888/1 and MR/N000048/1) and the British Heart Foundation for funding of the project grant (PG/15/12/31280)