7,8-Dihydro-8-oxoguanosine Lesions Inhibit the Theophylline Aptamer or Change Its Selectivity

Aptamers are attractive constructs due to their high affinity/selectivity towards a target. Here 7,8-dihydro-8-oxoguanosine (8-oxoG) has been used, due in part to its unique H-bonding capabilities (Watson–Crick or Hoogsteen), to expand the “RNA alphabet”. Its impact on the theophylline RNA aptamer was explored by modifying its binding pocket at positions G11, G25, or G26. Structural probing, with RNases A and T₁, showed that modification at G11 leads to a drastic structural change, whereas the G25-/G26-modified analogues exhibited cleavage patterns similar to that of the canonical construct. The recognition properties towards three xanthine derivatives were then explored through thermophoresis. Modifying the aptamer at position G11 led to binding inhibition. Modification at G25, however, changed the selectivity towards theobromine (K_d≈160 μm ), with a poor affinity for theophylline (K_d>1.5 mm ) being observed. Overall, 8-oxoG can have an impact on the structures of aptamers in a position-dependent manner, leading to altered target selectivity.     

Optimizing simultaneously over the numerator and denominator polynomials in the Youla-Kuc/spl caron/era parametrization

Traditionally, when approaching controller design with the Youla-Kuc/spl caron/era parametrization of all stabilizing controllers, the denominator of the rational parameter is fixed to a given stable polynomial, and optimization is carried out over the numerator polynomial. In this note, we revisit this design technique, allowing to optimize simultaneously over the numerator and denominator polynomials. Stability of the denominator polynomial, as well as fixed-order controller design with H/sub /spl infin// performance are ensured via the notion of a central polynomial and linear matrix inequality (LMI) conditions for polynomial positivity.     

Improved Prediction of Ozone Levels in Urban and Rural Atmospheres

Based on data obtained in terms of the first International cooperative program on the effects of acidic precipitations on materials (ICP Materials) of the United Nations European Commission on Economics (UN ECE), the relations between the ozone O₃ and nitrogen dioxide NO₂ concentrations in combination with the sunshine effect (taken into account either as the solar radiation (Rad) or the sunshine duration (Sun)) are considered. Analysis based on monthly and annual averages led to a new equation recommended for predicting ozone levels over rural, urban, and industrial areas of Europe as a function of NO₂ concentration and Sun parameter. Using Rad instead of Sun provides similar results, but, for practical usage, the equation involving a more easily available parameter Sun was recommended. The new equation corrects and improves the earlier proposed one, in which the concentration of ozone was given as a function of NO₂ concentration solely, and is included in the UN ECE Manual on mapping critical loads / levels and geographical areas where they are exceeded.     

Flexible polymer composite electromagnetic crystals

The dielectric properties of a ceramic powder (BaTiO₃) filled thermoplastic elastomer (EPDM TPE) were investigated for use in a flexible electromagnetic crystal. Materials were produced that had a high dielectric constant (approximately 9) and low loss tangent (less than 0.01). Materials were extruded and injection molded so as to povide low‐cost processing. Mechanical and electromagnetic test results showed the effect of processing conditions on the final quality of the composite. The shear rate during processing and the number of mixing cycles were found to affect the final material characteristics significantly. An electromagnetic crystal woven from extruded rods showed good reflectivity in the 10–15 GHz region.     

An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2

We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.     

Demonstration of Sustainable Development of Groundwater through Aquifer Storage and Recovery (ASR)

Water Resources Management - Sustained pumping of groundwater can lead to declining water levels in wellfields and concerns regarding the sustainability of groundwater resources. Aquifer Storage...     

Duration of slip-resistant shoe usage and the rate of slipping in limited-service restaurants: results from a prospective and crossover study

Several studies have indicated that slip-resistant shoes may have a positive effect on reducing the risk of slips and falls, a leading cause of injury at work. Few studies, however, have examined how duration of shoe usage affects their slip-resistance properties. This study examined the association between the duration of slip-resistant shoes usage and the self-reported rate of slipping in limited-service restaurant workers. A total of 475 workers from 36 limited-service restaurants in the USA were recruited to participate in a 12-week prospective study of workplace slipping. Of the 475 participants, 83 reported changing to a new pair of shoes at least once during the 12-week follow-up. The results show that slip-resistant shoes worn for less than six months were moderately more effective than those worn for more than six months. Changing to a new pair of shoes among those wearing slip-resistant shoes at baseline was associated with a 55% reduction in the rate of slipping (RR = 0.45, 95% CI = 0.23–0.89). Further research is needed to develop criteria for the replacement of slip-resistant shoes.

Practitioner Summary: The duration of usage impacts the slip-resistance properties of slip-resistant shoes. Slip-resistant shoes worn for less than six months were moderately more effective in reducing slips than slip-resistant shoes worn for more than six months. Shoe use policies should not only encourage or require their use but also include guidance on replacing slip-resistant shoes at regular intervals.     

Occupational slip, trip, and fall-related injuries--can the contribution of slipperiness be isolated?

To determine if the contribution of slipperiness to occupational slip, trip and fall (STF)-related injuries could be isolated from injury surveillance systems in the USA, the UK and Sweden, six governmental systems and one industrial system were consulted. The systems varied in their capture approaches and the degree of documentation of exposure to slipping. The burden of STF-related occupational injury ranged from 20 to 40% of disabling occupational injuries in the developed countries studied. The annual direct cost of fall-related occupational injuries in the USA alone was estimated to be approximately US$6 billion. Slipperiness or slipping were found to contribute to between 40 and 50% of fall-related injuries. Slipperiness was more often a factor in same level falls than in falls to lower levels. The evaluation of the burden of slipperiness was hampered by design limitations in many of the data systems utilized. The resolution of large-scale injury registries should be improved by collecting more detailed incident sequence information to better define the full scope and contribution of slipperiness to occupational STF-related injuries. Such improvements would facilitate the allocation of prevention resources towards reduction of first-event risk factors such as slipping.     

Confidential Incident Reporting on the UK Railways: The ‘CIRAS’ System

The paper describes CIRAS (Confidential Incident Reporting and Analysis System), a confidential reporting system developed by the authors in collaboration with ScotRail, the Health and Safety Executive, Railtrack and the (now defunct) British Rail Board. After a two-year pilot/developmental study with ScotRail during 1995–97, the system is now subscribed to by all but one of the major train operating companies, rail infrastructure and maintenance companies with a presence in Scotland; plus a developing profile in the rest of the UK.  CIRAS gathers data in three ways: (i) from an initial report form or telephone call, (ii) from a structured follow-up telephone questionnaire, and (iii) from an in-depth interview with a researcher (telephone or face-to-face, according to priority). The interviews bring to light details of personal motive, and of intended/unintended actions, which are not commonly found on company-run databases because of their association with disciplinary procedures. Information is processed through a human factors model and fed back to the companies involved, in disidentified form, to take corrective action.  The basic structure of the human-factors model is described; data are presented on reports received to date which have been processed through this model. The system has recently been recommended by a UK Parliamentary Committee and by Railtrack Safety and Standards Directorate for extension to the UK network as a whole.