Apparent specific volumes and tastes of cyclamates, other sulfamates, saccharins and acesulfame sweeteners

Measurements of apparent specific volume (ASV) for a series of alternative sweeteners (cyclamates, sulfamates, saccharins, acesulfames and anilinomethanesulfonates) have been made. Taste data have been obtained for many of the new compounds unless the toxicity of the associated metals precluded this. Apparent molar volume (AMV), isentropic specific (IASC) and isentropic molar (IAMC) compressibilities were also measured. Sixteen metallic cyclamates cyc-C6H11NHSO3M and two phenylsulfamates ArNHSO3Na, namely 3.5-dimethyl- and 3,4-dimethoxyphenylsulfamates have been examined. When the ASVs for these are combined with those for 15 aliphatic, aromatic and alicyclic sulfamates from a previous study, many of the values are seen to fall into the region that was previously identified as being the "sweet area", i.e. the ASVs lay between similar to0.5 and similar to0.7 (a few sweet compounds fall below this range and it is suggested that it could be extended slightly to accommodate these). Interestingly, the anilinomethanesulfonates, ArNHCH2SO3Na (Ar = C6H5-, 3-MeC6H4- and 3-ClC6H4-) lie clearly in the sweet region but only one of them shows slight sweetness showing that the molecular structural change made (compared with the 'parent' sulfamate-NHSO3-) cannot be accommodated at the receptor site. (C) 2003 Elsevier Ltd. All rights reserved.

Polymer-drug conjugates: current status and future trends

Polymer conjugates are nano-sized, multicomponent constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic drug delivery following endocytic capture. In the first part of this review, we analyze the promising results arising from clinical trials of polymer-bound chemotherapy. The experience gained on these studies provides the basis for the development of a more sophisticated second-generation of polymer conjugates. However, many challenges still lay ahead providing scope to develop and refine this field. The "technology platform'' of polymer therapeutics allows the development of both new and exciting polymeric materials, the incorporation of novel bioactive agents and combinations thereof to address recent advances in drug therapy. The rational design of polymer drug conjugates is expected to realize the true potential of these "nanomedicines".

Does repairing a cleft lip neonatally have any effect on the longer-term attractiveness of the repair?

Objective: To determine whether attractiveness and success of surgical outcome differ according to the timing of cleft lip repair. Design: Three experiments were conducted: (1) surgeons rated postoperative medical photographs of infants having either neonatal or 3-month lip repair; (2) lay panelists rated the same photographs; (3) lay panelists rated dynamic video displays of the infants made at 12 months. Normal comparison infants were also rated. The order of stimuli was randomized, and panelists were blind to timing of lip repair and the purposes of the study. Setting: Four U.K. regional centers for cleft lip and palate. Participants: Infants with isolated clefts of the lip, with and without palate. Intervention: Early lip repair was conducted at median age 4 days (inter-quartile range [IQR] = 4), and late repair at 104 days (IQR = 57). Main Outcome Measures: Ratings of surgical outcome (Experiment 1 only) and attractiveness (all experiments) on 5-point Likert scales. Results: In Experiment 1 success of surgical outcome was comparable for early and late repair groups (difference = -0.08; 95% confidence interval [CI] = -0.43 to 0.28; p = .66). In all three experiments, attractiveness ratings were comparable for the two groups. Differences were, respectively, 0.10 (95% CI = -2.3 to 0.44, p = .54); -0.11 (95% CI = -0.42 to -0.19, p = .54); and 0.08 (95% CI = -0.11 to 0.28, p =.41). Normal infants were rated more attractive than index infants (difference = 0.38; 95% CI = 0.24 to 0.52; p < .001). Conclusion: Neonatal repair for cleft of the lip confers no advantage over repair at 3 months in terms of perceived infant attractiveness or success of surgical outcome.

Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trial

Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances. Design Randomised controlled trial. Setting Khayelitsha, a peri-urban settlement in South Africa. Participants 449 pregnant women. Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team. Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months. Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=-2.04, P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=-1.76 (0.86), t=2.28, P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale). Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world. Trial registration Current Controlled Trials ISRCTN25664149.

The philosophy of W. Ross Ashby and its relationship to 'The Matrix'

Ashby was a keen observer of the world around him, as per his technological and psychiatrical developments. Over the years, he drew numerous philosophical conclusions on the nature of human intelligence and the operation of the brain, on artificial intelligence and the thinking ability of computers and even on science in general. In this paper, the quite profound philosophy espoused by Ashby is considered as a whole, in particular in terms of its relationship with the world as it stands now and even in terms of scientific predictions of where things might lead. A meaningful comparison is made between Ashby's comments and the science fiction concept of 'The Matrix' and serious consideration is given as to how much Ashby's ideas lay open the possibility of the matrix becoming a real world eventuality.

Adobe Garamond Premier Pro Greek

In 2003, through a conference presentation in Vancouver and a series of exchanges with Lemon, Leonidas convinced Adobe to substantially extend the coverage of the Greek script in forthcoming Adobe typefaces. The revised brief for Garamond was extended to include, for the first time in a digital typeface, extensive polytonic support, full archaic characters, and small capitals with optional polytonic diacritics; these features should be implemented with respect for the Greek language’s complex rules for case conversion, allowing full dictionary support regardless of the features applied. This project was the first where these issues were addressed, both from a documentation and a development point of view. Leonidas’ responsibilities lay with researching historical and current conventions, developing specifications for the appearance and behaviour of the typefaces, editing glyph outlines, and testing of development versions.

Achieving whole-life value: The challenges of service-led construction

Major construction clients are increasingly looking to procure built facilities on the basis of added value, rather than capital cost. Recent advances in the procurement of construction projects have emphasised a whole-life value approach to meeting the client’s objectives, with strategies put in place to encourage long-term commitment and through-life service provision. Construction firms are therefore increasingly required to take on responsibility for the operation and maintenance of the construction project on the client’s behalf - with the emphasis on value and service. This inevitably throws up a host of challenges, not the least of which is the need for construction firms to manage and accommodate the new emphasis on service. Indeed, these ‘service-led’ projects represent a new realm of construction projects where the rationale for the project is driven by client’s objectives with some aspect of service provision. This vision of downstream service delivery increases the number of stakeholders, adds to project complexity and challenges deeply-ingrained working practices. Ultimately it presents a major challenge for the construction sector. This paper sets out to unravel some of the many implications that this change brings with it. It draws upon ongoing research investigating how construction firms can adapt to a more service-orientated built environment and add value in project-based environments. The conclusions lay bare the challenges that firms face when trying to compete on the basis of added-value and service delivery. In particular, how it affects deeply-ingrained working practices and established relationships in the sector.

Regulation of expression of the rat orthologue of mouse double minute 2 (MDM2) by H2O2-induced oxidative stress in neonatal rat cardiac myocytes.

The Mdm2 ubiquitin ligase is an important regulator of p53 abundance and p53-dependent apoptosis. Mdm2 expression is frequently regulated by a p53 Mdm2 autoregulatory loop whereby p53 stimulates Mdm2 expression and hence its own degradation. Although extensively studied in cell lines, relatively little is known about Mdm2 expression in heart where oxidative stress (exacerbated during ischemia-reperfusion) is an important pro-apoptotic stimulus. We demonstrate that Mdm2 transcript and protein expression are induced by oxidative stress (0.2 mm H(2)O(2)) in neonatal rat cardiac myocytes. In other cells, constitutive Mdm2 expression is regulated by the P1 promoter (5' to exon 1), with inducible expression regulated by the P2 promoter (in intron 1). In myocytes, H(2)O(2) increased Mdm2 expression from the P2 promoter, which contains two p53-response elements (REs), one AP-1 RE, and two Ets REs. H(2)O(2) did not detectably increase expression of p53 mRNA or protein but did increase expression of several AP-1 transcription factors. H(2)O(2) increased binding of AP-1 proteins (c-Jun, JunB, JunD, c-Fos, FosB, and Fra-1) to an Mdm2 AP-1 oligodeoxynucleotide probe, and chromatin immunoprecipitation assays showed it increased binding of c-Jun or JunB to the P2 AP-1 RE. Finally, antisense oligonucleotide-mediated reduction of H(2)O(2)-induced Mdm2 expression increased caspase 3 activation. Thus, increased Mdm2 expression is associated with transactivation at the P2 AP-1 RE (rather than the p53 or Ets REs), and Mdm2 induction potentially represents a cardioprotective response to oxidative stress.

Built environment education and research in West Africa

Built environment programmes in West African universities; and research contributions from West Africa in six leading international journals and proceedings of the WABER conference are explored. At least 20 universities in the region offer degree programmes in Architecture (86% out of 23 universities); Building (57%); Civil Engineering (67%); Estate Management (52%); Quantity Surveying (52%); Surveying and Geoinformatics (55%); Urban and Regional Planning (67%). The lecturer-student ratio on programmes is around 1:25 compared to the 1:10 benchmark for excellence. Academics who teach on the programmes are clearly research active with some having published papers in leading international journals. There is, however, plenty of scope for improvement particularly at the highest international level. Out of more than 5000 papers published in six leading international peer-reviewed journals since each of them was established, only 23 of the papers have come from West Africa. The 23 papers are published by 28 academics based in 13 universities. Although some academics may publish their work in the plethora of journals that have proliferated in recent years, new generation researchers are encouraged to publish in more established journals. The analyses of 187 publications in the WABER conference proceedings revealed 18 research-active universities. Factors like quality of teaching, research and lecturer-student ratio, etc count in the ranking of universities. The findings lay bare some of the areas that should be addressed to improve the landscape of higher education in West Africa.

The decomposition of some RDX and HMX based materials in the one-dimensional time to explosion apparatus. Part 1. Time to explosion and apparent activation energy

A One-Dimensional Time to Explosion (ODTX) apparatus has been used to study the times to explosion of a number of compositions based on RDX and HMX over a range of contact temperatures. The times to explosion at any given temperature tend to increase from RDX to HMX and with the proportion of HMX in the composition. Thermal ignition theory has been applied to time to explosion data to calculate kinetic parameters. The apparent activation energy for all of the compositions lay between 127 kJ mol−1 and 146 kJ mol−1. There were big differences in the pre-exponential factor and this controlled the time to explosion rather than the activation energy for the process.

Built environment research in West Africa current trends and future directions

The countries in West Africa (WA) are pushing for socio-economic development. The construction sector has an important part to play in helping to realise these aspirations. This necessitates an increased emphasis on research in the built environment, as a key contributor to developing capacity, knowledge and technologies for the sector. The West Africa Built Environment Research (WABER) conference was initiated in 2008. The objective was to: help young built environment researchers in West Africa (WA) to develop their research work and skills through constructive face-to-face interaction with their peers and experienced international academics; supply a platform for interaction among more senior academics and an outlet for disseminating their research work; and to serve as a vehicle for developing the built environment field in Africa. Three conferences have so far been organised, 2009 - 2011, bringing together ~300 academics, researchers and practitioners from the WA region. This paper draws on content analysis of the 189 papers in the proceedings of three conferences: 2009 (25); 2010 (57) and 2011 (107). These papers provide a window into current research priorities and trends and, thus, offer an opportunity to understand the kinds of research work undertaken by built environment researchers in West Africa. The aim is to illuminate the main research themes and methods that are currently pursued and the limitations thereof. The findings lay bare some of the many challenges that are faced by academics in WA and provide suggestions for alternative directions for future research and development work with indications of a potential research agenda.

A comparison of the relative toxicity of bone meal and other P sources used as remedial treatments to the earthworm Eisenia fetida

It has been suggested that sources of P could be used to remediate metal-contaminated soil. The toxicity of four potential P sources, potassium hydrogen phosphate (PHP), triple superphosphate (TSP), rock phosphate (RP) and raw bone meal (RBM) to Eisenia fetida was determined. The concentration of P that is statistically likely to kill 50% of the population (LC50) for PHP, TSP and RBM was determined in OECD acute toxicity tests. 14 day LC50s expressed as bulk P concentration lay in the range 3319–4272 mg kg−1 for PHP, 3107–3590 mg kg−1 for TSP and 1782–2196 mg kg−1 for RBM (ranges present the 95% confidence intervals). For PHP and TSP mortality was significantly impacted by the electrical conductivity of the treated soils. No consistent relationship existed between mortality and electrical conductivity, soil pH and available (Olsen) P across the PHP, TSP and RBM amendment types. In RP toxicity tests mortality was low and it was not possible to determine a LC50 value. Incineration of bone meal at temperatures between 200 and 300 ◦C, pre-washing the bone meal, co-amendment with 5% green waste compost and delaying introduction of earthworms after bone meal amendments by 21 days or more led to significant reductions in the bone meal toxicity. These results are consistent with the toxicity being associated with the release and/or degradation of a soluble organic component present in raw bone meal. Bone meal can be used as an earthworm-friendly remedial amendment in metal-contaminated soils but initial additions may have a negative effect on any earthworms surviving in the contaminated soil before the organic component in the bone meal degrades in the soil.

Production and dissolution rates of earthworm-secreted calcium carbonate

Earthworms secrete granules of calcium carbonate. These are potentially important in soil biogeochemical cycles and are routinely recorded in archaeological studies of Quaternary soils. Production rates of calcium carbonate granules by the earthworm Lumbricus terrestris L. were determined over 27 days in a range of soils with differing chemical properties (pH, organic matter content, water holding capacity, bulk composition, cation exchange capacity and exchangeable cations). Production rate varied between soils, lay in the range 0–0.043 mmolCaCO3 (0–4.3 mg) earthworm−1 d−1 with an average rate of 8 × 10−3 mmolCaCO3 (0.8 mg) earthworm−1 d−1 and was significantly correlated (r = 0.68, P ≤ 0.01) with soil pH. In a second experiment lasting 315 days earthworms repeatedly (over periods of 39–57 days) produced comparable masses of granules. Converting individual earthworm granule production rates into fluxes expressed on per hectare of land per year basis depends heavily on estimates of earthworm numbers. Using values of 10–20 L. terrestris m−2 suggests a rate of 18– 3139 molCaCO3 ha−1 yr−1. Data obtained from flow-through dissolution experiments suggest that at near neutral pH, granule geometric surface areanormalised dissolution rates are similar to those for other biogenic and inorganic calcium carbonate. Fits of the data to the dissolution relationship r = k(1 − ˝)n where r = dissolution rate, k = a rate constant, ˝ = relative saturation and n = the reaction order gave values of k = 1.72 × 10−10 mol cm−2 s−1 and n = 1.8 for the geometric surface area-normalised rates and k = 3.51 × 10−13 mol cm−2 s−1 and n = 1.8 for the BET surface area-normalised rates. In 196 day leaching column experiments trends in granule dissolution rate referenced to soil chemistry corresponded to predictions made by the SLIM model for dissolution of limestone in soil. If soil solution approaches saturation with respect to calcium carbonate granule dissolution will slow or even stop and granules be preserved indefinitely. Granules have the potential to be a small but significant component of the biogeochemical cycling of C and Ca in soil.

Measuring the discrepancy between fecundity and lifetime reproductive success in a pollinating fig wasp

Lifetime reproductive success in female insects is often egg- or time-limited. For instance in pro-ovigenic species, when oviposition sites are abundant, females may quickly become devoid of eggs. Conversely, in the absence of suitable oviposition sites, females may die before laying all of their eggs. In pollinating fig wasps (Hymenoptera: Agaonidae), each species has an obligate mutualism with its host fig tree species [Ficus spp. (Moraceae)]. These pro-ovigenic wasps oviposit in individual ovaries within the inflorescences of monoecious Ficus (syconia, or ‘figs’), which contain many flowers. Each female flower can thus become a seed or be converted into a wasp gall. The mystery is that the wasps never oviposit in all fig ovaries, even when a fig contains enough wasp females with enough eggs to do so. The failure of all wasps to translate all of their eggs into offspring clearly contributes to mutualism persistence, but the underlying causal mechanisms are unclear. We found in an undescribed Brazilian Pegoscapus wasp population that the lifetime reproductive success of lone foundresses was relatively unaffected by constraints on oviposition. The number of offspring produced by lone foundresses experimentally introduced into receptive figs was generally lower than the numbers of eggs carried, despite the fact that the wasps were able to lay all or most of their eggs. Because we excluded any effects of intraspecific competitors and parasitic non-pollinating wasps, our data suggest that some pollinators produce few offspring because some of their eggs or larvae are unviable or are victims of plant defences.

Improving quality of mother-infant relationship and infant attachment in socioeconomically deprived community in South Africa: randomised controlled trail

Objective To assess the efficacy of an intervention designed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances. Design Randomised controlled trial. Setting Khayelitsha, a peri-urban settlement in South Africa. Participants 449 pregnant women. Interventions The intervention was delivered from late pregnancy and for six months postpartum. Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting. The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother. Women in the control group received no therapeutic input from the research team. Main outcome measures Primary outcomes: quality of mother-infant interactions at six and 12 months postpartum; infant attachment security at 18 months. Secondary outcome: maternal depression at six and 12 months. Results The intervention was associated with significant benefit to the mother-infant relationship. At both six and 12 months, compared with control mothers, mothers in the intervention group were significantly more sensitive (6 months: mean difference=0.77 (SD 0.37), t=2.10, P<0.05, d=0.24; 12 months: mean difference=0.42 (0.18), t=−2.04 , P<0.05, d=0.26) and less intrusive (6 months: mean difference=0.68 (0.36), t=2.28, P<0.05, d=0.26; 12 months: mean difference=−1.76 (0.86), t=2.28 , P<0.05, d=0.24) in their interactions with their infants. The intervention was also associated with a higher rate of secure infant attachments at 18 months (116/156 (74%) v 102/162 (63%); Wald=4.74, odds ratio=1.70, P<0.05). Although the prevalence of maternal depressive disorder was not significantly reduced, the intervention had a benefit in terms of maternal depressed mood at six months (z=2.05, P=0.04) on the Edinburgh postnatal depression scale). Conclusions The intervention, delivered by local lay women, had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment, factors known to predict favourable child development. If these effects persist, and if they are replicated, this intervention holds considerable promise for use in the developing world.