Novel colloidal materials for high-throughput screening applications in drug discovery and genomics

Tracking the reaction history is the means of choice to identify bioactive compounds in large combinatorial libraries. The authors describe two approaches to synthesis on silica beads: a) addition of a reporter dye tag during each synthesis step (see Figure), which attaches itself to the bead by colloidal forces, and b) encapsulating arrays of fluorescent dyes into the beads to encode them uniquely, for recognition with a flow cytometer after each reaction step.

MRI based diffusion and perfusion predictive model to estimate stroke evolution

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/-0.19 and 1.20 +/-0.36. For recovered tissue the mean values were 0.99 +/-0.25 and 1.87 +/-0.71, respectively. There was a significant difference between these two regions for both measures (P

A beam-forming network for a circular switched-beam phased array antenna

This paper reports on the design and development of a dividing/phasing network for a compact switched-beam array antenna for Land-vehicle mobile satellite communications, The device is formed by a switched radial divider/combiner and 1-bit phase shifters and generates a sufficient number of beams for the proper satellite tracking.

Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages

Activated monocytes and macrophages secrete the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) TNF-alpha is produced as a 26 kd transmembrane protein that is cleaved to release a 17 kd soluble protein. TNF-alpha in both forms is biologically active. The intracellular trafficking of membrane-associated TNF-alpha in lipopolysaccharide-activated mouse macrophages was assessed after treatment with the metalloprotease inhibitor BB-3103, which prevents the cleavage of pro-TNF-alpha. Immunoprecipitation and immunofluorescence studies showed sustained expression of cell-associated TNF-alpha in the presence of the inhibitor. Cell immunoreactivity and surface biotinylation revealed that uncleaved TNF-alpha accumulated on the cell surface and was endocytosed, appearing in intracellular vesicles. Perturbation of post-Golgi traffic blocked the surface expression of 26 kd TNF-alpha. Tracking a bolus of TNF-alpha over time in cycloheximide-treated cells confirmed that uncleaved TNF-alpha is first transported to the cell surface and subsequently endocytosed. Vesicular structures immunoreactive for TNF-alpha were identified as endosomes by double labeling. The secretory and membrane-associated endocytic trafficking of TNF-alpha provides a mechanism for modulating the quantity of biologically active 26 kd TNF-alpha expressed on macrophages, allowing regulation of paracrine and autocrine responses.

Maternal care and infant behaviour of the bridled nailtail wallaby (Onychogalea fraenata)

Bridled nailtail wallabies Onychogalea fraenata are endangered, medium-sized, nocturnal macropodids that persist at only one location in central Queensland, Australia. Characteristics of juvenile development, shelter use, anti-predator behaviour and maternal care were investigated in the wild using trapping, radio-tracking and spotlighting observations., Timing of developmental stages was identical to the pattern previously found in captivity, except for age at weaning which was much earlier in the wild. After young had left the pouch permanently at 17 weeks of age and weighing c. 800 g, they always spent the day concealed in dense cover, generally > 200 m from their mothers. Juveniles were also alone in > 50% of observations at night, and stayed closer to cover than did adult females. Young became independent of their mothers 7-8 weeks after permanent exit from the pouch and weighing c. 1800 g. Females with dependent juveniles changed their behaviour in ways likely to reduce predation on young. They reduced their home ranges, stayed closer to cover and became more wary than other females. Juveniles differed from adult females in their habitat use, anti-predator behaviour and shelter site preferences. Juveniles were more likely than adults to respond to threats by standing still or lying flat on the ground, whether or not they were in concealing cover. Juveniles used a wider range of smaller shelters than adults, and were less likely to use solid shelters such as hollow logs during the day. Because bridled nailtail wallabies have a 'hider' strategy of maternal care and the young rely on crypsis, successful breeding in the wild requires dense vegetation cover.

The influence of age on weight-bearing joint reposition sense of the knee

Knee joint-position sensitivity has been shown to decline with increasing age, with much of the research reported in the literature investigating this age effect in non-weight-bearing (NWB) conditions. However, little data is available in the more functional position of weight-bearing conditions. The objective of this study was to identify the influence of age on the accuracy and nature of knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial weight-bearing (PWB) conditions and to determine the effect of lower-extremity dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35 years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests were conducted on both the right and left legs to examine the ability of subjects to correctly reproduce knee angles in an active criterion-active repositioning paradigm. Knee angles were measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the test limb. Errors in FWB knee joint repositioning did not increase with age, but significant age-related increases in knee joint-repositioning error were found in PWB. It was found that elderly subjects tended to overshoot the criterion angle more often than subjects from the young and middle-aged groups. Subjects in all three age groups performed better in FWB than in PWB. Differences between the stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance. Results demonstrated that for, normal pain-free individuals, there is no age-related decline in knee JPS in FWB, although an age effect does exist in PWB. This outcome challenges the current view that a generalised decline in knee joint proprioception occurs with age. In addition, lower-limb dominance is not a factor in acuity of knee JPS.

Foraging by the endangered black-breasted button-quail (Turnix melanogaster) within fragmented rainforest of an agricultural landscape

We studied the foraging habitat of the endangered black-breasted button-quail (Turnix melanogaster) in 13 rainforest patches of an agricultural landscape (23.4 km(2)) in eastern Australia to assess its use of fragmented habitats outside conservation reserves. The species foraged only in the three largest patches (17.4, 40.0, 63.8 ha in size), all of which were connected to open eucalypt forest, and in intact rainforest. Occurrence of birds was greatest in the largest patch. The maximum number of individuals within the study area was estimated to be 22. Radio-tracking of nine birds revealed that three were resident in the largest patch for periods of over 100 days; no movements between patches were detected. Three radio-tagged birds were taken by avian and mammalian predators. Our results indicated that the long-term future of the species in agricultural landscapes is bleak and that management action is urgently needed to arrest its decline in these ecosystems, (C) 2001 Elsevier Science Ltd. All rights reserved.

Biodegradation of high strength phenolic wastewater using SBR

This investigation demonstrates the capability of a bench-scale sequencing batch reactor (SBR) to biodegrade an inhibitory substrate at a high loading rate. A SBR loading rate of 3.12 kg phenol.m(-3)d(-1) (2.1 g COD.g(-1) MLVSS d(-1)) with a COD removal efficiency of 97% at a SRT of 4 days and a HRT of 10 hours was achieved; this rate was not reached before. The SBR was operated at 4 hours cycle, including 3 hours react phase. The synthetic wastewater of 1300 mg/L phenol was the sole carbon source. Oxygen uptake rates (OUR) were monitored in-situ at various stages of the SBR. The oxygen mass transfer coefficient, K(L)a, of 12.6 h(-1) was derived from respirometry. Use of respirometry in SBR aided the tracking of the soluble substrate through OUR.

Reliability factors in business software: volatility, requirements and end-users

Many business-oriented software applications are subject to frequent changes in requirements. This paper shows that, ceteris paribus, increases in the volatility of system requirements decrease the reliability of software. Further, systems that exhibit high volatility during the development phase are likely to have lower reliability during their operational phase. In addition to the typically higher volatility of requirements, end-users who specify the requirements of business-oriented systems are usually less technically oriented than people who specify the requirements of compilers, radar tracking systems or medical equipment. Hence, the characteristics of software reliability problems for business-oriented systems are likely to differ significantly from those of more technically oriented systems.

Probing the time course of nonlinear discriminations during human electrodermal conditioning

Animal-based theories of Pavlovian conditioning propose that patterning discriminations are solved using unique cues or immediate configuring. Recent studies with humans, however, provided evidence that in positive and negative patterning two different rules are utilized. The present experiment was designed to provide further support for this proposal by tracking the time course of the allocation of cognitive resources. One group was trained in a positive patterning; schedule (A-, B-, AB+) and a second in a negative patterning schedule (A+, B+, AB-). Electrodermal responses and secondary task probe reaction time were measured. In negative patterning, reaction times were slower during reinforced stimuli than during non-reinforced stimuli at both probe positions while there were no differences in positive patterning. These results support the assumption that negative patterning is solved using a rule that is more complex and requires more resources than does the rule employed to solve positive patterning. (C) 2001 Elsevier Science (USA).

Effect of varying levels of mental workload on startle eyeblink modulation

Previous research using punctuate reaction time and counting tasks has found that the startle eyeblink reflex is sensitive to attentional demands. The present experiment explored whether startle eyeblink is also modulated during a complex continuous task and is sensitive to different levels of mental workload. Participants (N=14) performed a visual horizontal tracking task either alone (single-task condition) or in combination with a visual gauge monitoring task (multiple-task condition) for three minutes. On some task trials, the startle eyeblink reflex was elicited by a noise burst. Results showed that startle eyeblink was attenuated during both tasks and that the attenuation was greater during the multiple-task condition than during the single-task condition. Subjective ratings, endogenous eyeblink rate, heart period, and heart period variability provided convergent validity of the workload manipulations. The findings suggest that the startle eyeblink is sensitive to the workload demands associated with a continuous visual task. The application of startle eyeblink modulation as a workload metric and the possibility that it may be diagnostic of workload demands in different stimulus modalities is discussed.

Conformational changes in monolayers of a cationic amphiphilic porphyrin on saline subphases

Langmuir monolayer films of the tetracationic porphyrin tetrakis(octadecyl-4-pyridin ium)porphyrinatozinc(II) bromide on various salt containing subphases were analyzed using surface pressure-area isotherms and X-ray reflectivity. The use of these complementary techniques showed that the porphyrin molecules undergo changes in conformation upon compression. Two main phases were identified, one in which the porphyrin moiety is parallel to the subphase and one in which the porphyrin moiety is tilted out of the plane. The addition of different salts into the subphase brought about changes in film behaviour, which are explained in terms of a lyotropic series. Copyright (C) 2002 Society of Porphyrins,& Phthalocyanines.

Aboriginal and Torres Strait Islander health research and the conduct of longitudinal studies: issues for debate

The National Health and Medical Research Council, Research Agenda Working Group (RAWG), and the literature on Indigenous health have identified the need to fill gaps in descriptive data on Aboriginal and Torres Strait Islander health and noted both the lack of research with urban populations and the need for longitudinal studies. This paper presents some of the broad ethical and methodological challenges associated with longitudinal research in Indigenous health and focuses particularly on national studies and studies in urban areas. Our goal is to advance debate in the public health arena about the application of ethical guidelines and the conduct of longitudinal studies in Aboriginal and Torres Strait Islander communities. We encourage others to offer their experiences in this field.

Sensor-driven agenda for intelligent home care of the elderly

The exponential increase of home-bound persons who live alone and are in need of continuous monitoring requires new solutions to current problems. Most of these cases present illnesses such as motor or psychological disabilities that deprive of a normal living. Common events such as forgetfulness or falls are quite common and have to be prevented or dealt with. This paper introduces a platform to guide and assist these persons (mostly elderly people) by providing multisensory monitoring and intelligent assistance. The platform operates at three levels. The lower level, denominated ‘‘Data acquisition and processing’’performs the usual tasks of a monitoring system, collecting and processing data from the sensors for the purpose of detecting and tracking humans. The aim is to identify their activities in an intermediate level called ‘‘activity detection’’. The upper level, ‘‘Scheduling and decision-making’’, consists of a scheduler which provides warnings, schedules events in an intelligent manner and serves as an interface to the rest of the platform. The idea is to use mobile and static sensors performing constant monitoring of the user and his/her environment, providing a safe environment and an immediate response to severe problems. A case study on elderly fall detection in a nursery home bedroom demonstrates the usefulness of the proposal.