A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.

Helicoverpa armigera (Hubner): can wheat stubble protect cotton plants against attack?

When investigating strategies for Helicoverpa armigera (Hubner) control, it is important to understand oviposition behaviour. Cotton (Gossypium hirsutum) was sown into standing wheat (Triticum astivum L.) stubble in a closed arena to investigate the effect of stubble on H. armigera moth behaviour and oviposition. Infrared cameras were used to track moths and determine whether stubble acted as a physical barrier or provided camouflage to cotton plants, thereby reducing oviposition. Searching activity was observed to peak shortly before dawn (03:00 and 04:00 h) and remained high until just after dawn (4 h window). Moths spent more time resting on cotton plants than spiralling above them, and the least time flying across the arena. While female moths spent more time searching for cotton plants growing in wheat stubble, the difference in oviposition was not significant. As similar numbers of eggs were laid on cotton plants with stubble (3.5/plant SE +/- 0.87) and without stubble (2.5/plant SE +/- 0.91), wheat stubble does not appear to provide camouflage to cotton plants. There was no significant difference in the location of eggs deposited on cotton plants with and without stubble, although more eggs were laid on the tops of cotton leaves in wheat stubble. As the spatial and temporal distribution of eggs laid on the cotton plant is a crucial component of population stability, eggs laid on the upper side of leaves on cotton plants may be more prone to fatalities caused by environmental factors such as wind and rain. Therefore, although stubble did not influence the number of eggs laid, it did affect their distribution on the plant, which may result in increased mortality of eggs on cotton plants sown into standing wheat stubble.

Blind detection of PAM and QAM in fading channels

This correspondence considers block detection for blind wireless digital transmission. At high signal-to-noise ratio (SNR), block detection errors are primarily due to the received sequence having multiple possible decoded sequences with the same likelihood. We derive analytic expressions for the probability of detection ambiguity written in terms of a Dedekind zeta function, in the zero noise case with large constellations. Expressions are also provided for finite constellations, which can be evaluated efficiently, independent of the block length. Simulations demonstrate that the analytically derived error floors exist at high SNR.

Degenerate dentition of the dugong (Dugong dugon), or why a grazer does not need teeth: morphology, occlusion and wear of mouthparts

The morphology and functional occlusion of the cheekteeth of 57 dugongs Dugong dugon of both sexes were examined using reflected light and scanning electron microscopy, radiography, hardness testing and skull manipulation. The functional morphology of the horny oral pads was also described. Mouthparts and body size allometry was examined for ontogenetic and gender-related trends. We found that the worn erupted cheekteeth of the dugong are simple flat pegs composed of soft degenerative dentine. During occlusion, the mandible moves in a mainly antero-lingual direction, with the possibility of mandibular retraction in some individuals. Anterior parts of the cheektooth row may become non-functional as a dugong ages. As a function of body size, dugong cheekteeth are extremely small compared with those of other mammalian herbivores, and with other hindgut fermenters in particular. The morphology, small size and occlusal variability of the cheekteeth suggest that there has not been strong selective pressure acting to maintain an effective dentition. In contrast, great development of the horny pads and associated skull parameters and their lower size variability suggest that the horny pads may have assumed the major role in food comminution.

Effect of drying conditions on pyrethrins content

Windrowed pyrethrum stems were air dried under a range of storage conditions to examine whether the current commercial practice of drying crop material is conducive to pyrethrins' degradation. Crop material was stored for up to 12 days in a commercial windrow, a shed receiving indirect light or a dark, 5 degrees C cool-room. Analysis of pyrethrins extracted from flowers of all treatments demonstrated that pyrethrins were not degrading in windrowed crops, plant material stored in the shed or in the 5 degrees C cool-room. The small differences obtained in pyrethrins content among the treatments can be explained by the natural variation in pyrethrins content of pyrethrum crops. The observation that the achenes were unchanged during this drying period supported the pyrethrins analysis. These results demonstrate that pyrethrins in planta do not degrade as rapidly as extracted pyrethrins. (C) 2005 Elsevier B.V. All rights reserved.

Passive air sampling for persistent organic pollutants: Introductory remarks to the special issue

There have been a number of developments in the need, design and use of passive air samplers (PAS) for persistent organic pollutants (POPs). This article is the first in a Special Issue of the journal to review these developments and some of the data arising from them. We explain the need and benefit of developing PAS for POPs, the different approaches that can be used, and highlight future developments and needs. (c) 2006 Elsevier Ltd. All rights reserved.

Acibenzolar-S-methyl and methyl jasmonate treatments of glasshouse-grown freesias suppress post-harvest petal specking caused by Botrytis cinerea

Compounds that activate host plant defence responses potentially offer socio-environmentally sound alternative methods for disease control. In a series of glasshouse trials over 2 years, pre-harvest sprays with acibenzolar-S-methyl (ASM) and methyl jasmonate (MeJA) were tested for suppression of post-harvest infection of cut Freesia hybrida L. flowers by Botrytis cinerea. For the ASM treatments, variability in reducing the incidence of B. cinerea disease was observed between years freesia varieties, incubation temperatures and ASM concentrations. In the first year, the greatest reductions in lesion numbers on ASM-treated var. 'Cote d'Azur' were recorded using 2.86 mM ASM. For three different post-harvest temperature regimes, the relative reductions in lesion numbers, compared to untreated controls, were 45% at 5 degrees C, 40% at 12 degrees C and 30% at 20 degrees C, respectively. In the second year, lesion numbers were most reduced using 1.43 mM ASM to treat freesia var. 'Dukaat' flowers. Here, the relative reductions were to 44% at 5 degrees C, 26% at 12 degrees C and 51% at 20 degrees C. MeJA treatments were, in general, more consistently effective than ASM treatments in reducing lesion numbers and lesion diameters on cut freesia flowers. MeJA-treated (0.2 mM) freesia flowers (var. 'Dukaat') incubated at 20 degrees C showed relative reductions of 62%, and 45% for lesion number and lesion diameter, respectively. The differing efficacy between ASM and MeJA treatments could be attributed to their differential abilities to induce the salicylic acid (SA)-mediated vs. the jasmonic acid (JA)-mediated host defence pathways, respectively.

Why is economics not a complex systems science?

The article argues that economics will have to become a complex systems science before economists can comfortably incorporate institutionalist and evolutionary economics into mainstream theory. The article compares the complex adaptive system of John Foster with that of standard economic theory and illustrates the difference through an examination of familiar production function. The place of neoclassical, Keynesian economics in complex systems is considered. The article concludes that convincing, multiple models have been made possible by the increase in widely available computing power available.

Is modern medicine at risk of losing the plot?

Contemporary medicine has much to its credit, but has created an insatiable demand for new technologies and more health services, fed by commercial promotion, professional advocacy and sociopolitical pressure. Total health expenditure at the national level is now almost 10% of gross domestic product and is expected to top 16% by 2020. After recent inquiries into the failings of its public health system, the Queensland Government has committed itself to a 25% increase in expenditure on health over the next 5 years. But will it lead to better population health, and is it sustainable? The return-on-investment curve for modern health care may be flattening out, in an environment of growing numbers of older patients with chronic illnesses, maldistribution of services and hospital overcrowding. A change in thinking is required if current medical practice is to avoid imploding when confronted with the next major economic downturn. Health policy, service funding and clinical training must focus on critical appraisal of the effectiveness of health care technologies and the structure and financing of health care systems. Practising clinicians will be obliged to provide leadership in determining value for money in the choice of health care for specific patient populations and how that care is delivered.

Engineering of needle-free physical methods to target epidermal cells for DNA vaccination

A challenge in epidermal DNA vaccination is the efficient and targeted delivery of polynucleotides to immunologically sensitive Langerhans cells. This paper investigates this particular challenge for physical delivery approaches. The skin immunology and material properties are examined in the context of the physical cell targeting requirements of the viable epidermis. Selected current physical cell targeting technologies engineered to meet these needs are examined: needle and syringe; diffusion patches; liquid jet injectors; microneedle arrays/patches; and biolistic particle injection. The operating methods and relative performance of these approaches are discussed, with a comment on potential future developments and technologies. (c) 2005 Elsevier Ltd. All rights reserved.

Liberal Democracy and the Inferior 'Other'Other’: Could the peace liberal democracy promises to bring not extend to ‘Others’?

Advocates of liberal democracy argue that its principles and practices contribute directly to peace (at both inter-state and domestic levels). They rely on ideals such as the rule of law, institutional checks and balances on power, an ethos of tolerance, and free market economics to deliver the liberal peace. Liberals, however, overlook three important features embedded in the construction of liberal democracy which can serve to facilitate political violence: 1) the fixed and thus non-negotiable nature of liberal democracy’s core principles, 2) the inferior manner in which it conceives ‘Other’ social orders that do not share its core principles, and 3) the urge to proselytise Others. Together, these constitutive qualities can facilitate moves by leaders of Other groups to argue that liberal democracy threatens ‘their’ preferred identity, and thus its promised peaceful outcomes can be put in doubt.

Overcoming the problem of loss-in-capacity of calcium oxide in CO2 capture

Calcium oxide has been identified to be one of the best candidates for CO2 capture in zero-emission power-generation systems. However, it suffers a well-known problem of loss-in-capacity (i.e., its capacity of CO2 capture decreases after it undergoes cycles of carbonation/decarbonation). This problem is a potential obstacle to the adoption of the new technologies. This paper proposes a method of fabricating a CaO-based adsorbent without the problem of loss-in-capacity. An adsorbent was fabricated using the method and tested on a thermogravimetric analyzer. It was shown that the sorbent attained a utilization efficiency of more than 90% after 9 cycles of carbonation/decarbonation.