33,037 research outputs found

    Suicide substrate reaction-diffusion equations: varying the source

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    The suicide substrate reaction is a model for certain enzyme-inhibiting drugs. This reaction system is examined assuming that the substrate diffuses freely while the enzyme remains fixed. Two sets of initial and boundary conditions are examined: one modelling an instantaneous point source, akin to an injection of substrate, the other, a continuous point source, akin to a continuing influx, or intravenous drip, of substrate. The quasi-steady-state assumption is applied to obtain analytical solutions for a limited parameter space. Finally, further applications of numerical and analytical experimentation on pharmaceutical mechanisms are described

    On the kinetics of suicide substrates

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    We consider a realistic suicide substrate reaction which can be represented by four rate equations for the concentrations of the various molecules as functions of time. We present a general procedure to obtain accurate, approximate solutions analytically in terms of the rate equation parameters. This systematic technique provides more accurate approximations to the exact (numerical) solutions than other approximate methods which have been proposed based on a pseudo-steady state hypothesis

    Understanding decision making among individuals With Intellectual and Developmental Disabilities (IDD) and their siblings

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    Many siblings anticipate fulfilling caregiving roles for their brothers and sisters with intellectual and developmental disabilities (IDD). Given these roles and the importance of supported decision-making, it is crucial to understand how individuals with IDD and their siblings make decisions. Using dyadic interviews, we examined the perspectives of nine sibling dyads (N = 18) about decision-making in relation to self-determination, independent living, and employment. The ages of participants ranged from 19 to 57. Data were analyzed using constant comparative analysis to identify themes. Decision-making was characterized by: parents and siblings primarily identifying courses of action; the probability of respective consequences based on the person-environment fit; and the role of the sibling in making the final decision. Characteristics related to the individual with IDD, the family, the sibling, and the environment impacted decision-making. Individuals with IDD were more likely to make their own decisions about leisure activities, however, siblings were more likely to make formal decisions for their brothers and sisters.Accepted manuscrip

    Group versus individual approach? A meta-analysis of the effectiveness of interventions to promote physical activity

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    The purpose of the study was to conduct a meta-analysis to empirically compare the relative merits of different contexts typically employed in the physical activity intervention literature for five categories of outcomes: adherence, social interaction, quality of life, physiological effectiveness, and functional effectiveness. \ud Four contexts were examined: home-based programmes not involving contact from researchers or health-care professionals, home-based programmes that involved some contact, standard exercise classes, and exercise classes where group-dynamics principles were used to increase cohesiveness (‘true groups’). Standard literature searches produced 44 relevant studies containing 214 effect sizes. Results revealed a common trend across dependent variables; exercising in a true group was superior to exercising in a standard exercise class, which in turn, did not differ from exercising at home with contact. Furthermore, exercising at home with contact was superior to exercising at home without contact. These results have implications for practitioners in terms of the importance of contact and social support in physical activity interventions

    Analysis of band-gap formation in squashed arm-chair CNT

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    The electronic properties of squashed arm-chair carbon nanotubes are modeled using constraint free density functional tight binding molecular dynamics simulations. Independent from CNT diameter, squashing path can be divided into {\it three} regimes. In the first regime, the nanotube deforms with negligible force. In the second one, there is significantly more resistance to squashing with the force being ∼40−100\sim 40-100 nN/per CNT unit cell. In the last regime, the CNT looses its hexagonal structure resulting in force drop-off followed by substantial force enhancement upon squashing. We compute the change in band-gap as a function of squashing and our main results are: (i) A band-gap initially opens due to interaction between atoms at the top and bottom sides of CNT. The π−\pi-orbital approximation is successful in modeling the band-gap opening at this stage. (ii) In the second regime of squashing, large π−σ\pi-\sigma interaction at the edges becomes important, which can lead to band-gap oscillation. (iii) Contrary to a common perception, nanotubes with broken mirror symmetry can have {\it zero} band-gap. (iv) All armchair nanotubes become metallic in the third regime of squashing. Finally, we discuss both differences and similarities obtained from the tight binding and density functional approaches.Comment: 16 pages and 6 figures, To appear in PR

    Alloreactive cytotoxic T lymphocytes generated in the presence of viral- derived peptides show exquisite peptide and MHC specificity

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    The nature of alloreactivity to MHC molecules has been enigmatic, primarily because of the observation that allogeneic responses are considerably stronger than syngeneic responses. To better determine the specificity potential of allogeneic responses, we have generated alloreactive CTL specific for exogenous, viral-derived peptide ligands. This approach allowed us to critically evaluate both the peptide- and MHC-specificity of these alloreactive T cells. Exploiting the accessibility of the H-2Ld class I molecule for exogenous peptide ligands, alloreactive CTL were generated that are specific for either murine cytomegalovirus (MCMV) or lymphocytic choriomeningitis virus (LCMV) peptides bound by Ld alloantigens. Peptide specificity was initially observed in bulk cultures of alloreactive CTL only when tested on peptide-sensitized T2.Ld target cells that have defective presentation of endogenous peptides. Subsequent cloning of bulk alloreactive CTL lines generated to MCMV yielded CTL clones that had exquisitely specific MCMV peptide recognition requirement. All of the MCMV/Ld alloreactive CTL clones were also exquisitely MHC-specific in that none of the CTL clones lysed targets expressing MCMV/Lq complexes, even though Lq differs from Ld by only six amino acid residues and Lq also binds the MCMV peptide. This observation clearly demonstrates that alloreactive CTL are capable of the same degree of specificity for target cell recognition as are syngeneic CTL in MHC-restricted responses

    The Kara and Ust-Kara impact structures (USSR) and their relevance to the K/T boundary event

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    The Kara and Ust-Kara craters are twin impact structures situated at about 69 deg 10 min N; 65 deg 00 min E at the Kara Sea. For Kara a diameter of about 55 km would be a very conservative estimate, and field observations indicate a maximum current diameter of about 60 km. The diameter of Ust-Kara has to be larger than 16 km. A better estimate might be 25 km but in all likelihood it is even larger. Suevites and impactites from the Kara area have been known since the beginning of the century, but had been misidentified as glacial deposits. Only about 15 years ago the impact origin of the two structures was demonstrated, following the recognition of shock metamorphism in the area. The composition of the target rocks is mirrored by the composition of the clasts within the suevites. In the southern part of Kara, Permian shales and limestones are sometimes accompanied by diabasic dykes, similar to in the central uplift. Due to the high degree of shock metamorphism the shocked magmatic rocks are not easily identified, although most of them seem to be of diabasic or dioritic composition. The impact melts (tagamites) are grey to dark grey fine grained crystallized rocks showing very fine mineral components and are the product of shock-melting with later recrystallization. The impact glasses show a layered structure, inclusions, and vesicles, and have colors ranging from translucent white over brown and grey to black. A complete geochemical characterization of the Kara and Ust-Kara impact craters was attempted by analyzing more than 40 samples of target rocks, shocked rocks, suevites, impact melts, and impact glasses for major and trace elements

    Average and worst-case specifications of precipitating auroral electron environment

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    The precipitation electrons in the auroral environment are highly variable in their energy and intensity in both space and time. As such they are a source of potential hazard to the operation of the Space Shuttle and other large spacecraft operating in polar orbit. In order to assess these hazards both the average and extreme states of the precipitating electrons must be determined. Work aimed at such a specification is presented. First results of a global study of the average characteristics are presented. In this study the high latitude region was divided into spatial elements in magnetic local time and corrected geomagnetic latitude. The average electron spectrum was then determined in each spatial element for seven different levels of activity as measured by K sub p using an extremely large data set of auroral observations. Second a case study of an extreme auroral electron environment is presented, in which the electrons are accelerated through field aligned potential as high as 30,000 volts and in which the spacecraft is seen to charge negatively to a potential approaching .5 kilovolts
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