The repeatability of self-reported exposure after miscarriage

BACKGROUND: The Avon Longitudinal Study of Pregnancy and Childhood is a prospective study of women who were resident in Avon and who were expected to deliver a baby between April 1991 and December 1992. METHODS: The study provided an opportunity to test the repeatability of responses from 220 women who experienced a miscarriage and who reported exposure to occupational substances and common household products and appliances in two questionnaires. The first questionnaire was completed in the early part of the pregnancy and the second after the miscarriage. Women were asked to score their frequency of exposure on a five-point scale from 'daily' to 'never'. Their responses were analysed to assess the degree of agreement between replies to identical questions in the two questionnaires using the kappa statistic. A new frequency variable was created which compared the replies for the two questionnaires; this was analysed for all exposures by cross-tabulation with possible explanatory variables (age of mother, social class, history of miscarriage and the time lag between questionnaires). RESULTS: In general there was good agreement in the reported exposures to 48 substances and products. The results showed a small and consistent pattern of reporting exposures less frequently in the second questionnaire, i.e. after miscarriage. This was not explained by the analysis of possible confounding variables. Given the literature, the authors had expected to find a shift in the opposite direction. CONCLUSION: The study reinforces the need to be cautious when using the results from single surveys of retrospective self-reported exposure

Holidaying with the family pet: No dogs allowed!

This paper assesses the extent to which dog owners located in Brisbane, Australia, wish to holiday with their pets, and whether there is a gap between this desire and reality. The paper also examines the extent to which this demand is being catered for by the tourism accommodation sector. The need for this study reflects the increasingly significant role dogs are playing in the lives of humans, and the scale of the dog-owning population. The results suggest that, although there is a strong desire among dog owners to take holidays with their pets, the actualisation of this desire is comparatively low. A significant obstacle to the realisation of this desire appears to be a dearth of pet-friendly accommodation. This has implications for the ability of the tourism industry to benefit from this potentially lucrative market, that is, the dog-owning population

Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Comparative transcriptomic analysis of plum fruit treated with 1-MCP

Microarray technology has allowed the large scale transcriptomic analysis of fruit ripening. The μPEACH1.0 microarray containing 4,806 probes corresponding to genes expressed in peach fruit tissues has been used in a heterologous fashion in two studies of plums ripening behavior. Gene expression of different cultivars of plums treated with the ethylene antagonist, 1-methylcyclopropene (1-MCP) and stored for short periods at room temperature or for longer periods of cold storage was examined. In the first study, mature fruit of a suppressed ethylene climacteric cultivar 'Shiro' and a cultivar characterized by a typical increase of ethylene production during ripening ('Santa Rosa') were harvested and incubated for 24h in air (control) or 1-MCP and allowed to ripen at room temperature. Different levels of transcripts of genes implicated in cell wall metabolism, hormone (ethylene and auxin) regulation, stress and defense, and in the transcription/translation machinery, as well as others involved with ripening were identified. In the second study, the effects of 1-MCP on gene expression in relation to the development of chilling injury (CI) in the climacteric cultivars 'Ruby Red' (RR) and 'October Sun' (OS) and 'Zee Lady' peaches (ZP) were analyzed. The fruit were treated for 24h at room temperature with 1-MCP prior to storage at 0°C. For RR, there was no significant effect of 1-MCP on the level of CI symptoms, while 1-MCP significantly reduced CI symptoms in OS fruit and an increase of CI in treated ZP fruit. Microarray analysis showed that immediately following treatment, 186, 134 and 56 genes were differentially expressed between the control and 1-MCP-treated fruit of these cultivars, respectively: after 4 weeks cold storage, 311, 52 and 224 genes for RR, OS and ZP, respectively, were differentially expressed between control and treated fruit. Thus, for OS, the number of differentially expressed genes reduced during storage while the number increased in RR and ZP. Comparisons of the data suggest that the transcript profile is altered by 1-MCP more in plums than peaches. These studies, carried out within an international collaborative network, will increase our understanding of the regulation of pathways involved in plum fruit ripening and in metabolic processes related to storage and shelf lif

UK Large-scale Wind Power Programme from 1970 to 1990: the Carmarthen Bay experiments and the Musgrove Vertical-Axis Turbines

This article describes the development of the Musgrove Vertical Axis Wind Turbine (VAWT) concept, the UK ‘Carmarthen Bay’ wind turbine test programme, and UK government’s wind power programme to 1990. One of the most significant developments in the story of British wind power occurred during the 1970s, 1980s, and 1990s, with the development of the Musgrove vertical axis wind turbine and its inclusion within the UK Government’s wind turbine test programme. Evolving from a supervisor’s idea for an undergraduate project at Reading University, the Musgrove VAWT was once seen as an able competitor to the horizontal axis wind systems that were also being encouraged at the time by both the UK government and the Central Electricity Generating Board, the then nationalised electricity utility for England and Wales. During the 1980s and 1990s the most developed Musgrove VAWT system, along with three other commercial turbine designs was tested at Carmarthen Bay, South Wales as part of a national wind power test programme. From these developmental tests, operational data was collected and lessons learnt, which were incorporated into subsequent wind power operations.http://dx.doi.org/10.1260/03095240677860621

Potentiation of anti-cancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors NU1025 and NU1064.

The ability of the potent poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025 (8-hydroxy-2-methyl-quinazolin-4-[3H]one) to potentiate the cytotoxicity of a panel of mechanistically diverse anti-cancer agents was evaluated in L1210 cells. NU1025 enhanced the cytotoxicity of the DNA-methylating agent MTIC, gamma-irradiation and bleomycin 3.5-, 1.4- and 2-fold respectively. The cytotoxicities of the thymidylate synthase inhibitor, nolatrexed, and the cytotoxic nucleoside, gemcitabine, were not increased. Potentiation of MTIC cytotoxicity by a delayed exposure to NU1025 was equally effective as by a simultaneous exposure to NU1025, indicating that the effects of NU1025 were mediated by an inhibition of the cellular recovery. The recovery from potentially lethal gamma-irradiation damage cytotoxicity in plateau-phase cells was also inhibited by NU1025. Investigation of DNA strand breakage and repair in gamma-irradiated cells by alkaline elution demonstrated that NU1025 caused a marked retardation of DNA repair. A structurally different PARP inhibitor, NU1064 (2-methylbenzimidazole-4-carboxamide), also potentiated the cytotoxicity of MTIC, to a similar extent to NU1025. NU1064 potentiated a sublethal concentration of a DNA methylating agent in a concentration-dependent manner. Collectively, these data suggest that the most suitable cytotoxic agents for use in combination with PARP inhibitors are methylating agents, bleomycin and ionizing radiation, but not anti-metabolites

Suppression of prion protein in livestock by RNA interference

Given the difficulty of applying gene knockout technology to species other than mice, we decided to explore the utility of RNA interference (RNAi) in silencing the expression of genes in livestock. Short hairpin RNAs (shRNAs) were designed and screened for their ability to suppress the expression of caprine and bovine prion protein (PrP). Lentiviral vectors were used to deliver a transgene expressing GFP and an shRNA targeting PrP into goat fibroblasts. These cells were then used for nuclear transplantation to produce a cloned goat fetus, which was surgically recovered at 81 days of gestation and compared with an age-matched control derived by natural mating. All tissues examined in the cloned fetus expressed GFP, and PCR analysis confirmed the presence of the transgene encoding the PrP shRNA. Most relevant, Western blot analysis performed on brain tissues comparing the transgenic fetus with control demonstrated a significant (>90%) decrease in PrP expression levels. To confirm that similar methodologies could be applied to the bovine, recombinant virus was injected into the perivitelline space of bovine ova. After in vitro fertilization and culture, 76% of the blastocysts exhibited GFP expression, indicative that they expressed shRNAs targeting PrP. Our results provide strong evidence that the approach described here will be useful in producing transgenic livestock conferring potential disease resistance and provide an effective strategy for suppressing gene expression in a variety of large-animal models

Scaling and crossovers in activated escape near a bifurcation point

Near a bifurcation point a system experiences critical slowing down. This leads to scaling behavior of fluctuations. We find that a periodically driven system may display three scaling regimes and scaling crossovers near a saddle-node bifurcation where a metastable state disappears. The rate of activated escape $W$ scales with the driving field amplitude $A$ as $\ln W \propto (A_c-A)^{\xi}$, where $A_c$ is the bifurcational value of $A$. With increasing field frequency the critical exponent $\xi$ changes from $\xi = 3/2$ for stationary systems to a dynamical value $\xi=2$ and then again to $\xi=3/2$. The analytical results are in agreement with the results of asymptotic calculations in the scaling region. Numerical calculations and simulations for a model system support the theory.Comment: 18 page

Flow Analysis of the Cleveland Clinic Centrifugal Pump

An implantable ventricular assist rotordynamic blood pump is being developed by the Cleveland Clinic Foundation in cooperation with the NASA Lewis Research Center. At the nominal design condition, the pump provides blood flow at the rate of 5 liters per minute at a pressure rise of 100 mm of mercury and a rotative speed of 3000 RPM. Bench testing of the centrifugal pump in a water/glycerin mixture has provided flow and pressure data at several rotative speeds. A one-dimensional empirical based pump flow analysis computer code developed at NASA Lewis Research Center has been used in the design process to simulate the flow in the primary centrifugal pump stage. The computer model was used to size key impeller and volute geometric parameters that influence pressure rise and flow. Input requirements to the computer model include a simple representation of the pump geometry. The model estimates the flow conditions at the design and at off-design operating conditions at the impeller leading and trailing edges and the volute inlet and exit. The output from the computer model is compared to flow and pressure data obtained from bench testing

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds