Electrical Current Signatures of DNA Base Modifications in Single Molecules Immobilized in the α-Hemolysin Ion Channel

Nanopore technology holds high potential for next-generation DNA sequencing. This method operates by drawing an individual single-stranded DNA molecule through a nanoscale pore, while monitoring the current deflections that occur as the DNA passes through. Individual current levels for the four DNA nucleotides have been established by immobilization of an end biotinylated strand in the pore, in which the nucleotide of interest is suspended at the most sensitive region of the ion channel. Due to the inherent reactivity of DNA bases, many modified nucleotides in the genome exist as a result of oxidative and UV insults, among others. Herein, the current levels for common DNA damage lesions 8-oxo-7,8-dihydroguanine, spiroiminodihydantoin, guanidinohydantoin, uridine, abasic sites, thymine dimers, thymine glycol, and 5-iodocytosine were assessed through immobilization experiments. In some cases, the current difference between the damaged and canonical nucleotides was not well resolved; therefore, we took advantage of the chemical reactivity of the new functional groups present to make amine adducts that shifted the current levels outside the range of the native nucleotides. Among the adducts studied, only the 2-aminomethyl-18-crown-6 adduct was able to give a large current shift in the immobilization experiment, as well as being observed in a translocation experiment. The results show potential in providing current-level modulators for identification of some types of DNA damage. In principle, any DNA base modification that can be converted chemically or enzymatically into an abasic site could be identified in this way.     

A user modeling approach for reasoning about interaction sensitive to bother and its application to hospital decision scenarios

In this paper, we present a framework for interacting with users that is sensitive to the cost of bother and then focus on its application to decision making in hospital emergency room scenarios. We begin with a model designed for reasoning about interaction in a single-agent single-user setting and then expand to the environment of multiagent systems. In this setting, agents consider both whether to ask other agents to perform decision making and at the same time whether to ask questions of these agents. With this fundamental research as a backdrop, we project the framework into the application of reasoning about which medical experts to interact with, sensitive to possible bother, during hospital decision scenarios, in order to deliver the best care for the patients that arrive. Due to the real-time nature of the application and the knowledge-intensive nature of the decisions, we propose new parameters to include in the reasoning about interaction and sketch their usefulness through a series of examples. We then include a set of experimental results confirming the value of our proposed approach for reasoning about interaction in hospital settings, through simulations of patient care in those environments. We conclude by pointing to future research to continue to extend the model for reasoning about interaction in multiagent environments for the setting of time-critical care in hospital settings.     

Ovine arylalkylamine N-acetyltransferase in the pineal and pituitary glands: differences in function and regulation

The enzyme arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) has been conventionally linked with the biosynthesis of melatonin within the pineal gland and retina. This study establishes that AANAT messenger RNA (mRNA) and functional enzyme occurs within the pars tuberalis (PT) and to a lesser degree within the pars distalis (PD) of the sheep pituitary gland; expression in these tissues is approximately 1/15th (PT) and 1/300th (PD) of that in the ovine pineal gland. AANAT mRNA in the PT appears to be expressed in the same cells as the Mel1a receptor. No evidence was obtained to indicate that either PT or PD cells have the ability to synthesize melatonin, suggesting that this enzyme plays a different functional role in the pituitary. We also found that cAMP regulation of the abundance of AANAT mRNA differs between the PT and pineal gland. Forskolin (10 microM) has no effect on pineal AANAT mRNA levels, yet represses expression in the PT. This suppressive influence could be mediated by ICER (inducible cAMP response early repressor), which is induced by forskolin in both tissues. Although it appears that the specific function and regulation of AANAT in the pituitary gland differ from that in the pineal gland, it seems likely that AANAT may play a role in the broader area of signal transduction through the biotransformation of amines.     

Development of controlled strength-loss resorbable beta-tricalcium phosphate bioceramic structures

Controlling the strength-loss rate during biodegradation is a bottleneck in developing viable resorbable ceramic implants. Resorbable beta-tricalcium phosphate (β-TCP) bioceramic is known for its excellent biocompatibility. However, it exhibits poor sinterability and poor flexural strength. Here, we improved sintering behavior and biaxial flexural strength of β-TCP bioceramic without altering its biocompatibility by introducing multi-oxide sintering additives, in small quantities. These additives could also tailor the rate of resorption and hardness deterioration of β-TCP. A range of additives were prepared and introduced into β-TCP powder. Resultant powders were uniaxially pressed and sintered at 1250 °C, in air. Considerable improvement in densification (up to 33%) and biaxial flexural strength (up to 43%) were achieved. X-ray powder diffraction (XRD) analysis confirmed that the additives didn't alter the phase purity. In vitro cytotoxicity and biocompatibility analyses were performed using a prostate cancer cell-line. Results showed that the doped and pure β-TCP structures were non-toxic and biocompatible.     

Electric field enhanced nanocrystal formation in thermally poled optical fibres

High-resolution scanning electron microscopy has been utilised to characterise the structural change in optical fibres after being thermally poled. A layer of nanometre-sized crystals has been found 5.5 /spl mu/m beneath the anode surface. The strong electric field formed under the anode is believed to have enhanced the nucleation process.     

Correspondence: Images of native Americans II

Abstract

The Navajo people of the American Southwest have been abundantly photographed since the beginnings of photography's extension into Western America — indeed, from almost since the beginnings of photography itself. Navajoland ‘offered’ dramatic landscapes and ‘The People’¹ have served as exemplar for an assorted series of Western projects, changes in Western projects, and objects of Western desire. The photographs of Native Americans by Edward S. Curtis, though largely ignored during his lifetime, emerged shortly after his death in 1952 to become popular icons, which were so dramatic a phenomenon from the 1960s that today they are something of a cliché. ‘Original’ prints currently sell for thousands of dollars.² This resurrection is also characteristic among specialists on Native Americans. Indeed, after having been neglected and abused by anthropology for many years for his elaborate staging, soft focus, excessive pastoral romanticism and nostalgia, Curtis has more recently become fashionable again and now enjoys something of an anthropological embrace.³