16 research outputs found

    Frustration of Contractual Purpose--Doctrine or Myth?

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    Remedies Under Rule 10b-5

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    The Changes in The Compressive and Tensile Yield Strengths During Uniaxial Cyclic Loading

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    80 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1983.Many of the multiaxial unified-creep plasticity theories which have been proposed as a means to improve design at elevated temperatures have suffered from the drawback that the manner in which the state variables change is difficult to measure. A unified creep-plasticity theory for uniaxial loading which uses the yield strengths in tension, Y(,1), and compression, Y(,2), as the state variables is investigated as the means of improving the formulation of such theories. The yield strengths are easily measured and can be readily transformed to the state variables commonly used in the multiaxial theories.The yield strengths were measured during a completely reversed cyclic strain amplitude history for 304 stainless steel at 23(DEGREES)C and 600(DEGREES)C, and for Inconel 751 at 788(DEGREES)C and 927(DEGREES)C. The data from these experiments were then plotted in the (Y(,1),Y(,2)) plane and a geometric model of how the state variables change during loading was constructed.The model clearly demonstrates that on each loading reversal kinematic hardening is the predominate type of hardening. The observed limit cycle behavior of the state variables requires that there be an isotropic softening, or decrease in the elastic range, at the beginning of each reversal. This is followed by a rapid isotropic hardening at the end of the reversal. However, this behavior was obscured by the scatter in the data which was on the order of 10 percent of the elastic range.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

    Deconstructing risk: Separable encoding of variance and skewness in the brain

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    Risky choice entails a need to appraise all possible outcomes and integrate this information with individual risk preference. Risk is frequently quantified solely by statistical variance of outcomes, but here we provide evidence that individuals’ choice behaviour is sensitive to both dispersion (variance) and asymmetry (skewness) of outcomes. Using a novel behavioural paradigm in humans, we independently manipulated these ‘summary statistics’ while scanning subjects with fMRI. We show that a behavioural sensitivity to variance and skewness is mirrored in neuroanatomically dissociable representations of these quantities, with parietal cortex showing sensitivity to the former and prefrontal cortex and ventral striatum to the latter. Furthermore, integration of these objective risk metrics with subjective risk preference is expressed in a subject-specific coupling between neural activity and choice behaviour in anterior insula. Our findings show that risk is neither monolithic from a behavioural nor neural perspective and its decomposition is evident both in distinct behavioural preferences and in segregated underlying brain representations

    Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

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    BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen
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