Impact failure in two silicates revealed by ultrafast, in situ, synchrotron X-ray microscopy.

To travel safely behind screens that can protect us from stones and hail, we must understand the response of glass to impact. However, without a means to observe the mechanisms that fail different silicate architectures, engineering has relied on external sensors, post-impact examination and best-guess to glaze our vehicles. We have used single and multi-bunch, X-ray imaging to differentiate distinct phases of failure in two silicates. We identified distinct micromechanisms, operating in tandem and leading to failure in borosilicate glass and Z-cut quartz. A surface zone in the amorphous glass densifies before bulk fracture occurs and then fails the block, whilst in quartz, fast cracks, driven down cleavage planes, fails the bulk. Varying the rate at which ejecta escapes by using different indenter tip geometries controls the failed target's bulk strength. This opens the way to more physically based constitutive descriptions for the glasses allowing design of safer, composite panels by controlling the impulses felt by protective screens.

Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer).

Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

On compression and damage evolution in two thermoplastics.

The well-known Taylor cylinder impact test, which follows the impact of a flat-ended cylindrical rod onto a rigid stationary anvil, is conducted over a range of impact speeds for two polymers, polytetrafluoroethylene (PTFE) and polyetheretherketone (PEEK). In previous work, experiments and a model were developed to capture the deformation behaviour of the cylinder after impact. These works showed a region in which spatial and temporal variation of both longitudinal and radial deformation provided evidence of changes in phase within the material. In this further series of experiments, this region is imaged in a range of impacted targets at the Diamond synchrotron. Further techniques were fielded to resolve compressed regions within the recovered polymer cylinders that showed a fracture zone in the impact region. The combination of macroscopic high-speed photography and three-dimensional X-ray imaging has identified the development of failure with these polymers and shown that there is no abrupt transition in behaviours but rather a continuous range of responses to competing operating mechanisms. The behaviours noted in PEEK in these polymers show critical gaps in understanding of polymer high strain-rate response.

Dynamic damage in carbon-fibre composites.

The Taylor test is used to determine damage evolution in carbon-fibre composites across a range of strain rates. The hierarchy of damage across the scales is key in determining the suite of operating mechanisms and high-speed diagnostics are used to determine states during dynamic loading. Experiments record the test response as a function of the orientation of the cylinder cut from the engineered multi-ply composite with high-speed photography and post-mortem target examination. The ensuing damage occurs during the shock compression phase but three other tensile loading modes operate during the test and these are explored. Experiment has shown that ply orientations respond to two components of release; longitudinal and radial as well as the hoop stresses generated in inelastic flow at the impact surface. The test is a discriminant not only of damage thresholds but of local failure modes and their kinetics. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'.

Production of a high-velocity water slug using an impacting technique.

A pulsed water jet consists of a series of discrete water slugs travelling at high velocity. Immediately after striking a target, these slugs apply high-intensity, short-duration transient stress pulses reaching an amplitude known as the water hammer pressure, followed by low-intensity, long-duration stationary stress at a lower stagnation pressure. The magnitude and duration of the water hammer and stagnation pressures are controlled by the size and quality of the water slugs. The use of water jets for rock cutting in mining operations is a centuries-old technology; however, practical methods for producing high-energy water slugs repeatedly have proven difficult. This can be partly due to the fact that the geometrical properties of a jet and so its effectiveness in creating damage is controlled and influenced by the method that is employed to generate the water slugs. This paper investigates the quality of a single water slug produced using an impacting technique where a hammer strikes a piston, resting on top of a water-filled chamber. The coherence and integrity of the jet core was of concern in this study. The impact impulse of the formed water jet was measured in a Kel-F target material using an embedded PVDF (Polyvinylidene fluoride) shock gauge. The recorded stress waveform was then used to determine the unity and endurance of the water slug stream once travelled through air.

Evidence that leptin genotype is associated with fertility, growth, and milk production in Holstein cows.

This study investigated associations between single nucleotide polymorphisms (SNP) in the leptin, leptin receptor, and neuropeptide Y (NPY) genes with growth, milk production, and fertility traits. Holstein Friesian heifers from 19 UK dairy farms were recruited at birth, providing an initial population of 509. Animals were monitored until they either reached the end of their second lactation or were culled. Size (weight, height, length, girth) was measured at 1, 6, and 15 mo to assess growth traits. Heifer fertility was assessed by recording age at service, age at conception, age at first calving, and number of services. Cow fertility was assessed by recording days from calving to service and conception, services per conception, percentage of animals in calf at 100 d after calving and the calving interval in each lactation. Milk production was recorded as days in milk, total milk per lactation, 305-d yield, milk per day, and peak yield. Mixed model analyses revealed that leptin SNP were associated with early skeletal growth (height, A1457G; length, A59V), fertility (UASMS1, UASMS2, A1457G, A59V) and milk production (A59V). The leptin receptor SNP (T945M) was only weakly associated with milk per day and days to first service. The NPY SNP (NPY1) was associated with the prevalence of the animal being in calf 100 d after calving and 305-d milk yield in the first lactation. The association of leptin SNP with fertility traits in heifers, in addition to lactating cows, suggests that some effects on fertility are direct and not necessarily mediated via altered tissue mobilization. In accord with this, other work has shown that leptin can affect oocyte quality and early embryo development. These results support the use of leptin SNP to inform marker-assisted selection in dairy cows.

Polymorphisms in the autosomal genes for mitochondrial function TFAM and UCP2 are associated with performance and longevity in dairy cows.

The autosomal genes mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2) are both involved in moderating mitochondrial energy production. This study investigated single nucleotide polymorphisms (SNPs) in TFAM and UCP2 and their associations with growth, fertility, milk production and survival in UK dairy cows. Holstein-Friesian heifers (n = 509) were recruited at birth and monitored until they either reached the end of their second lactation or were culled. Weight, height, length and girth were measured at 1, 6 and 15 months of age to assess growth. Fertility records were obtained for both heifers and cows and production traits (milk per day, peak yield and 305-day yield) were recorded in the first and second lactation. Mixed model and survival analyses revealed that TFAM3 GG homozygotes, representing 49% of the population, were larger than the AG heterozygotes throughout the growing period, had worse fertility, produced less milk in both lactations and were more likely to be culled. TFAM3 AA homozygotes (7% of population) were generally smaller as heifers, had slightly worse fertility and also produced less milk. This suggests a clear advantage for maximizing the heterozygotic population for this SNP. Furthermore, the results for milk per day suggest an overdominant effect, as both homozygotes of TFAM3 had significantly lower yields than the heterozygote. For UCP2, the minority CG heterozygotes (6% of population) were larger as heifers, had a reduced age at first conception and a delayed return to cyclicity after calving, when compared against the majority (94%) GG homozygotes.

Effect of growth and development during the rearing period on the subsequent fertility of nulliparous Holstein-Friesian heifers.

This study investigated the effect of growth parameters and metabolic indices during the rearing period on the fertility of nulliparous Holstein-Friesian heifers managed on 17 UK dairy farms. Growth parameters (body weight [BW], heart girth, height, and crown-rump length) and metabolic indices (insulin-like growth factor-I [IGF-I], insulin, glucose, and urea) were measured at approximately 30, 180, and 450 d of age. Fertility data collected included age at first breeding (AFB), number of services per conception, pregnancy rate to first artificial insemination (AI), and age at first calving (AFC). Of the heifers initially bred (n=428), 4% failed to conceive. The mean pregnancy rate to first AI for heifers that conceived and calved without suffering reproductive loss (n=392) was 67%, and 6% required >2 inseminations. The mean AFB and AFC was 473+/-5 d (range, 357 to 936 d) and 791+/-6 d (range, 636 to 1529 d), respectively. Increased BW, girth, and IGF-I concentration (at 30, 180, and 450 d) and increased skeletal growth (at 180 and 450 d) was associated with a reduced AFB and AFC (P<0.05 to 0.001). Heifers calving at <775 d had a mean BW gain of 0.82+/-0.01kg from 30 to 180 d. Increased glucose concentration at 180 d was associated with a reduced AFB (P<0.01), but no associations were found between insulin and urea concentrations and any of the fertility traits recorded (P>0.1). Suboptimal growth associated with an increased AFC could be alleviated by improved monitoring of replacement heifers during the rearing period.

Metabolic traits affecting growth rates of pre-pubertal calves and their relationship with subsequent survival.

This study related growth and metabolic traits in Holstein-Friesian calves (n=45) to subsequent performance and longevity. Animals were measured at birth, 3, 6 and 9 months (weight, crown rump length (CRL), heart girth and height). Endocrine and metabolic traits were assessed at 6 months of age. These traits were not influenced by sire (n=5). Milk production and mortality records were obtained through 3 lactations. Seven heifers failed to achieve a lactation, 6 were culled after one, 17 after two and 15 (33%) survived >/=3 lactations. Birth weight and girth but not skeletal measures were highly positively correlated with the repeated size measurements at 3-9 months. Calves with higher cortisol at 6 months were smaller in weight and girth at 3 months, with reduced 3-6 months skeletal growth. GH secretion was related to height, weight and growth, whereas urea was most strongly related to CRL. Calves not achieving a single lactation had lower IGF-I. Calves with higher glucose or BHB were more likely to be culled after 2 lactations, an effect which was independent of yield. Size and metabolic measurements of growing calves may therefore prove useful in predicting longevity.

Factors influencing heifer survival and fertility on commercial dairy farms.

The average dairy cow survives only three lactations, reducing the availability of replacement heifers. Prenatal losses occur due to early embryonic mortality (about 40%), later embryo loss (up to 20% in high-yielding herds) or abortion (about 5%). A recent survey of 19 UK herds showed that 7.9% of calves were born dead and 3.4% died within 1 month. During the rearing phase, 6.7% of animals were lost before reaching first service at 15 months due to disease or accident and another 2.3% failed to conceive. Many potential replacements therefore never enter the milking herd. This severely limits opportunities for on-farm selection of breeding cows in addition to presenting a welfare issue and causing economic loss. The most profitable animals once lactation is reached combine good milk production with a regular calving pattern. Some aspects of performance are related to age at first calving (AFC), which in turn is influenced by heifer growth rates. Poorly growing animals required more services to conceive, calved later and subsequently performed badly. Optimum fertility and maximum yield in the first lactation were associated with an AFC of 24 to 25 months. However, heifers calving at 22 to 23 months performed best in terms of total milk yield and survival over the first 5 years, partly because good heifer fertility was associated with better fertility later. We have investigated some possible juvenile predictors of future performance. Low-birth-weight calves were more likely to come from either primiparous mothers or older dams (3+ lactations) with higher peak milk yields, suggesting that the uterine environment may limit prenatal calf growth due to competition for nutrients with maternal growth or milk production. Linear trait classification scores for frame size show genetic correlations with longevity. The skeletal measures of height and crown rump length in 1-month-old calves was correlated to subsequent stature, and frame size was correlated to weight at 15 months. It may thus be possible to predict performance from simple size measurements as juveniles. Neither endogenous nor stimulated growth hormone (GH) release in 6-month-old calves were related to milk yield in the first three lactations, but size of a stimulated GH peak was positively related to milk energy values in the first lactation. Cows with delayed ovulation (>45 days) in the first lactation had a higher GH pulse amplitude and lower IGF-I as a juvenile. Cows that partition excess energy into milk in their first lactation may suffer reduced longevity.

The effect of parenteral supplementation of vitamin E with selenium on the health and productivity of dairy cattle in the UK.

Recent work has suggested that the recommended intakes of vitamin E for dairy cattle need to be increased, particularly in dry cows. However, these suggestions are based on data from cattle in the USA, which may have significantly different oxidative stresses than European cattle. This study, which involved 594 cattle on three dairy farms, was designed to determine the effect of increased vitamin E supplementation on the health and fertility of UK dairy cows. Cattle were randomly allocated to receive either two intramuscular injections of 2100 mg of vitamin E (and 7 g of sodium selenite) 2 weeks before calving and on the day of calving, or no additional vitamin E supplementation. Although supplementation had no effect on milk yield, reproductive efficiency, or incidence of uterine infections, supplemented cattle had a lower risk of culling and a lower rate of mastitis. These figures were economically significant but not statistically significant at the 10% level. Supplementation reduced the incidence of retained fetal membranes from 6.5% to 3%, an effect which was almost significant at the 5% level. If these data are representative they suggest that vitamin E recommendations for UK cattle should be reassessed.

Influence of negative energy balance on cyclicity and fertility in the high producing dairy cow.

The peripartum period is of critical importance to subsequent health and fertility. Most cows enter a state of negative energy balance (NEB) associated with many metabolic changes which have carry over effects on the resumption and normality of estrous cyclicity and the success of subsequent inseminations. A dataset on 500 lactations explored the relationships between metabolic traits measured before and after calving with fertility. Stepwise multiple regression analysis showed that longer calving to conception intervals were associated with altered profiles of IGF-I, urea and body condition score. These relationships between metabolic profiles and fertility differed between first lactation cows (which are still growing but produce less milk) and mature animals. Early postpartum the liver undergoes extensive biochemical and morphological modifications to adapt to NEB, the uterus is extensively remodeled and must clear bacterial infections, and the ovary must resume ovulatory cycles. RNA isolated from liver and uterine tissues harvested 2 weeks postpartum from cows in mild (MNEB) and severe (SNEB) energy balance was used to screen the Affymetrix 23K bovine microarray. In liver, SNEB resulted in differential expression of key genes involved in lipid catabolism, gluconeogenesis, and the synthesis and stability of IGF-I. This was accompanied by reduced systemic concentrations of IGF-I which is likely to impact on ovarian function and early embryo development. Within endometrium, cows in SNEB showed histological evidence for higher levels of inflammation and the microarray analysis identified groups of differentially expressed genes involved in tissue remodeling and immune response. This may delay uterine repair after calving, likely contributing to the observed reduction in fertility.

Multiple correlation analyses of metabolic and endocrine profiles with fertility in primiparous and multiparous cows.

Results from 4 studies were combined (representing a total of 500 lactations) to investigate the relationships between metabolic parameters and fertility in dairy cows. Information was collected on blood metabolic traits and body condition score at 1 to 2 wk prepartum and at 2, 4, and 7 wk postpartum. Fertility traits were days to commencement of luteal activity, days to first service, days to conception, and failure to conceive. Primiparous and multiparous cows were considered separately. Initial linear regression analyses were used to determine relationships among fertility, metabolic, and endocrine traits at each time point. All metabolic and endocrine traits significantly related to fertility were included in stepwise multiple regression analyses alone (model 1), including peak milk yield and interval to commencement of luteal activity (model 2), and with the further addition of dietary group (model 3). In multiparous cows, extended calving to conception intervals were associated prepartum with greater concentrations of leptin and lesser concentrations of nonesterified fatty acids and urea, and postpartum with reduced insulin-like growth factor-I at 2 wk, greater urea at 7 wk, and greater peak milk yield. In primiparous cows, extended calving to conception intervals were associated with more body condition and more urea prepartum, elevated urea postpartum, and more body condition loss by 7 wk. In conclusion, some metabolic measurements were associated with poorer fertility outcomes. Relationships between fertility and metabolic and endocrine traits varied both according to the lactation number of the cow and with the time relative to calving.

Differences between primiparous and multiparous dairy cows in the inter-relationships between metabolic traits, milk yield and body condition score in the periparturient period.

During the early postpartum period dairy cows mobilize fat and muscle to support lactation. This is associated with alterations in blood metabolite and hormone profiles which in turn influence milk yield and fertility. This study developed models to determine how metabolic traits, milk yield and body condition score were inter-related at different times in the periparturient period and to compare these relationships in primiparous (PP, n=188) and multiparous (MP, n=312) cows. Data from four previous studies which included information on blood metabolic parameters, parity, milk yield, body condition score and diet were collated into a single dataset. Coefficients of polynomial equations were calculated for each trait between -1 week pre-calving and week +7 postpartum using residual maximum likelihood modelling. The completed dataset was used in a multiple correlation model to determine how the best fit curves were related to each other over time. PP cows had higher concentrations of insulin-like growth factor-I and lower beta-hydroxybutyrate concentrations throughout, higher leptin concentrations pre-partum and both the peak in non-esterified fatty acids and the nadir in urea concentration occurred earlier after calving. These differences were associated with significantly lower milk production. Leptin concentrations fell at calving and were related to body condition score. Insulin was negatively correlated with yield in MP cows only. In MP cows the relationship between insulin-like growth factor-I and yield switched from negative to positive between weeks +4 and +7. Both beta-hydroxybutyrate and urea were positively related to yield in PP cows. In contrast, in MP cows beta-hydroxybutyrate was negatively correlated with yield and urea was strongly related to body condition score but not yield. These results suggest that there are differences in the control of tissue mobilization between PP and MP cows which may promote nutrient partitioning into growth as well as milk during the first lactation.

A meta-analysis of the effects of Vitamin E supplementation on the incidence of retained foetal membranes in dairy cows.

A meta-analysis was performed to consolidate the results of studies which have evaluated the effects of Vitamin E supplementation during the dry period on the risk of retained foetal membranes (RFM) in the dairy cow. Twenty studies demonstrated a beneficial response to Vitamin E whilst 21 found no benefit and 3 reported an increase in the incidence of RFM in treated cows. The odds ratios (OR) of the available studies exhibited significant heterogeneity, so multivariable logistic regression analysis was performed to enable the identification of factors associated with the response to Vitamin E supplementation. Our multivariable analysis included parity and Vitamin E supplementation (control/treated) in the model, because all other factors were co-linear. Results indicated that Vitamin E supplementation led to a reduction in the incidence of RFM. A second multivariable analysis was undertaken on a subset of the data including only supplemented cows to determine the influence of supplementation factors on the risk of RFM. All factors were co-linear with each other, therefore, only type of Vitamin E supplementation was included in this analysis. The regression model demonstrated that administration of the synthetic Vitamin E alpha-tocopheryl acetate was associated with a lower risk of RFM than treatment with natural Vitamin E (alpha-tocopherol) (P=0.047, OR=0.49), whereas the difference between the synthetic Vitamin E alpha-tocopherol acetate and natural Vitamin E just failed to attain statistical significance (P=0.059, OR=0.53). Overall the analyses indicate that Vitamin E supplementation during the dry period is associated with a reduced risk of RFM, and that the synthetic forms of Vitamin E are more effective than the natural compound.

Dynamic plasticity and failure of high-purity alumina under shock loading.

Most high-performance ceramics subjected to shock loading can withstand high failure strength and exhibit significant inelastic strain that cannot be achieved under conventional loading conditions. The transition point from elastic to inelastic response prior to failure during shock loading, known as the Hugoniot elastic limit (HEL), has been widely used as an important parameter in the characterization of the dynamic mechanical properties of ceramics. Nevertheless, the underlying micromechanisms that control HEL have been debated for many years. Here we show high-resolution electron microscopy of high-purity alumina, soft-recovered from shock-loading experiments. The change of deformation behaviour from dislocation activity in the vicinity of grain boundaries to deformation twinning has been observed as the impact pressures increase from below, to above HEL. The evolution of deformation modes leads to the conversion of material failure from an intergranular mode to transgranular cleavage, in which twinning interfaces serve as the preferred cleavage planes.

Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.

Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

Poly(sodium 4-styrene sulfonate): evaluation of a topical microbicide gel against herpes simplex virus type 2 and Chlamydia trachomatis infections in mice.

OBJECTIVE: To investigate the in vivo activity of poly(sodium 4-styrene sulfonate) (T-PSS) gel formulations as topical microbicides. METHODS: The ability of the gel formulations to reduce the incidence of infection when applied prior to pathogen challenge was examined in mouse models of vaginal herpes simplex type 2 (HSV-2) and Chlamydia trachomatis infection, and rectal HSV-2 infection. RESULTS: In the vaginal HSV-2 challenge studies, 10% T-PSS gel provided significant protection against infection, even when administered 60 min prior to virus challenge (P < 0.0001). Both 5% and 10% T-PSS gel formulations significantly reduced the incidence of upper genital tract C. trachomatis infection in animals treated up to 5 min before challenge (P < 0.001). However, no protection against C. trachomatis infection was seen in animals treated 30 min before challenge. In mice challenged rectally with HSV-2, both the 5% and 10% T-PSS gels significantly reduced infection at 20 s (P < 0.01 for both). However, only the 10% gel provided significant protection when administered 5 min before challenge (P < 0.01). CONCLUSIONS: T-PSS gel formulations have promising in vivo activity as topical microbicides.