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N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.
Dry wind-tunnel (DWT) flutter test systems model the unsteady distributed aerodynamic force using various electromagnetic exciters. They can be used to test the aeroelastic and aeroservoelastic stability of smart aircraft or high-speed flight vehicles. A new parameterised modelling method at the full system level based on the generalised force equivalence for DWT flutter systems is proposed herein. The full system model includes the structural dynamic model, electromechanical coupling model and fast aerodynamic computation model. An optimisation search method is applied to determine the best locations for measurement and excitation by introducing Fisher’s information matrix. The feasibility and accuracy of the proposed system-level numerical DWT modelling method have been validated for a plate aeroelastic model with four exciters/transducers. The effects of key parameters including the number of exciters, the control time delay, the noise interference and the electrical parameters of the electromagnetic exciter model have also been investigated. The numerical and experimental results indicate that the proposed modelling method achieves good accuracy (with deviations of less than 1.5% from simulations and 4.5% from experimental test results for the flutter speed) and robust performance even in uncertain environments with a 10% noise level.
ABSTRACT IMPACT: This study evaluates the long term effects of pharmacologic weaning therapy for opiate exposed infants. OBJECTIVES/GOALS: Infants born to chronic opioid users often suffer from neonatal abstinence syndrome (NAS), a condition characterized by tremors, diarrhea, hyperirritability and an inconsolable high-pitched cry. Symptoms are treated with pharmacologic weaning therapy, but long-term effects of this treatment have not been established. METHODS/STUDY POPULATION: A sample of infants born between 2011-2017 was obtained from a large metropolitan hospital system. All infants who were exposed to opioids and received a Finnegan score were included in the sample (N=1,807). The analysis utilizes three dependent variables to measure developmental delay: motor delay, language delay or any delay, which includes general/non-specific delay in addition to motor and language delay. The treatment is defined as receipt of pharmacologic therapy with methadone or morphine. Maximum Finnegan score was also included as a continuous measure of the extent of the infant’s withdrawal symptoms. Linear models were utilized to determine a relationship between pharmacologic therapy and developmental delay with Maximum Finnegan score as an interaction term. RESULTS/ANTICIPATED RESULTS: In the linear models examining the main effects of weaning therapy on developmental delay, there was no relationship between pharmacologic therapy and motor delay (p=.260), language delay (p=.542) or any developmental delay (p=.176). When maximum Finnegan score was entered into the model as an interaction term the relationships were not significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results suggest that while pharmacologic weaning is an appropriate treatment for withdrawal symptoms in infants, it is not a deterrent against developmental delays associated with NAS. This provides support suggest an increased focus on non-pharmacologic interventions such as breastfeeding as the first line of treatment for NAS infants.
To estimate the prevalence of thinness, overweight and obesity among Tibetan adolescents aged 12–17 years.
Shigatse City of Tibet municipality, with an average altitude of more than 4000 m.
Study participants included 2642 adolescents aged 12–17 years selected from six schools using a convenient cluster sampling method.
The prevalence of thinness/overweight/obesity among Tibetan adolescents was 9·4 %/5·4 %/1·4 % (China definition), 14·7 %/4·4 %/0·7 % (International Obesity Task Force (IOTF) definition), and 2·8 %/5·7 %/0·9 % (WHO definition). The prevalence of thinness and overweight was significantly different between both sexes based on each of three BMI classification criteria (P < 0·001). There was no significant difference in the prevalence of obesity between both sexes according to each of three BMI criteria. There was no clear trend in the prevalence of thinness across ages according to the China or IOTF definition (both P > 0·05), whereas an upward trend was observed for thinness in boys according to the IOTF definition (Pfor trend <0·05). In contrast, the prevalence of thinness tended to decrease with increasing age in girls according to the IOTF definition and in total sample according to the WHO definition (Pfor trend <0·05).
Among Tibetan adolescents, the prevalence of overweight and obesity is relatively low, while the prevalence of thinness is high, especially in boys. These data suggest urgent attention is needed to control adolescent thinness in Tibet.
To investigate the influences of dietary riboflavin (RF) addition on nutrient digestion and rumen fermentation, eight rumen cannulated Holstein bulls were randomly allocated into four treatments in a repeated 4 × 4 Latin square design. Daily addition level of RF for each bull in control, low RF, medium RF and high RF was 0, 300, 600 and 900 mg, respectively. Increasing the addition level of RF, DM intake was not affected, average daily gain tended to be increased linearly and feed conversion ratio decreased linearly. Total tract digestibilities of DM, organic matter, crude protein (CP) and neutral-detergent fibre (NDF) increased linearly. Rumen pH decreased quadratically, and total volatile fatty acids (VFA) increased quadratically. Acetate molar percentage and acetate:propionate ratio increased linearly, but propionate molar percentage and ammonia-N content decreased linearly. Rumen effective degradability of DM increased linearly, NDF increased quadratically but CP was unaltered. Activity of cellulase and populations of total bacteria, protozoa, fungi, dominant cellulolytic bacteria, Prevotella ruminicola and Ruminobacter amylophilus increased linearly. Linear increase was observed for urinary total purine derivatives excretion. The data suggested that dietary RF addition was essential for rumen microbial growth, and no further increase in performance and rumen total VFA concentration was observed when increasing RF level from 600 to 900 mg/d in dairy bulls.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA−) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA− diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA− diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.
Bisphenol-A (BPA) is associated with adverse health outcomes and is found in many canned foods. It is not understood if some BPA contamination can be washed away by rinsing. The objective of this single-blinded crossover experiment was to determine whether BPA exposure, as measured by urinary concentrations, could be decreased by rinsing canned beans prior to consumption. Three types of hummus were prepared from dried beans, rinsed, and unrinsed canned beans. Fourteen healthy participants ate two samples of each hummus over six experimental days and collected spot urine specimens for BPA measurement. The geometric mean BPA levels for dried beans BPA (GM = 0.97 ng/ml, 95%CI = 0.74,1.26) was significantly lower than rinsed (GM = 1.89 ng/ml, 1.37,2.59) and unrinsed (GM = 2.46 ng/ml, 1.44,4.19). Difference-in-difference estimates showed an increase in GM BPA from pre- to post-hummus between unrinsed and rinsed canned beans of 1.39 ng/ml, p-value = 0.0400. Rinsing canned beans was an effective method to reduce BPA exposure.
To investigate the value of narrow-band imaging training for differentiating between benign and malignant vocal fold leukoplakia.
Thirty cases of vocal fold leukoplakia were selected.
Narrow-band imaging endoscopy training had a significant positive effect on the specificity of the differential diagnosis of vocal fold leukoplakia. In addition, the consistency of diagnostic typing of vocal fold leukoplakia by narrow-band imaging improved to ‘moderate agreement’ following the combination of types I and II and the combination of types IV, V and VI in the typing of vocal fold leukoplakia.
The narrow-band imaging training course may improve the ability of laryngologists to diagnose vocal fold leukoplakia. The new endoscopic diagnostic classification by narrow-band imaging needs to be further simplified to facilitate clinical application.
Antarctica's ice shelves modulate the grounded ice flow, and weakening of ice shelves due to climate forcing will decrease their ‘buttressing’ effect, causing a response in the grounded ice. While the processes governing ice-shelf weakening are complex, uncertainties in the response of the grounded ice sheet are also difficult to assess. The Antarctic BUttressing Model Intercomparison Project (ABUMIP) compares ice-sheet model responses to decrease in buttressing by investigating the ‘end-member’ scenario of total and sustained loss of ice shelves. Although unrealistic, this scenario enables gauging the sensitivity of an ensemble of 15 ice-sheet models to a total loss of buttressing, hence exhibiting the full potential of marine ice-sheet instability. All models predict that this scenario leads to multi-metre (1–12 m) sea-level rise over 500 years from present day. West Antarctic ice sheet collapse alone leads to a 1.91–5.08 m sea-level rise due to the marine ice-sheet instability. Mass loss rates are a strong function of the sliding/friction law, with plastic laws cause a further destabilization of the Aurora and Wilkes Subglacial Basins, East Antarctica. Improvements to marine ice-sheet models have greatly reduced variability between modelled ice-sheet responses to extreme ice-shelf loss, e.g. compared to the SeaRISE assessments.
The aerodynamic performance of a deployable and low-cost unmanned aerial vehicle (UAV) is investigated and improved in present work. The parameters of configuration, such as airfoil and winglet, are determined via an optimising process based on a discrete adjoint method. The optimised target is locked on an increasing lift-to-drag ratio with a limited variation of pitching moments. The separation that will lead to a stall is delayed after optimisation. Up to 128 design variables are used by the optimised solver to give enough flexibility of the geometrical transformation. As much as 20% enhancement of lift-to-drag ratio is gained at the cruise angle-of-attack, that is, a significant improvement in the lift-to-drag ratio adhering to the preferred configuration is obtained with increasing lift and decreasing drag coefficients, essentially entailing an improved aerodynamic performance.
Coated copper sulphate (CCS) could be used as a Cu supplement in cows. To investigate the influences of copper sulphate (CS) and CCS on milk performance, nutrient digestion and rumen fermentation, fifty Holstein dairy cows were arranged in a randomised block design to five groups: control, CS addition (7·5 mg Cu/kg DM from CS) or CCS addition (5, 7·5 and 10 mg Cu/kg DM from CCS, respectively). When comparing Cu source at equal inclusion rates (7·5 mg/kg DM), cows receiving CCS addition had higher yields of fat-corrected milk, milk fat and protein; digestibility of DM, organic matter (OM) and neutral-detergent fibre (NDF); ruminal total volatile fatty acid (VFA) concentration; activities of carboxymethyl cellulase, cellobiase, pectinase and α-amylase; populations of Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter succinogenes; and liver Cu content than cows receiving CS addition. Increasing CCS addition, DM intake was unchanged, yields of milk, milk fat and protein; feed efficiency; digestibility of DM, OM, NDF and acid-detergent fibre; ruminal total VFA concentration; acetate:propionate ratio; activity of cellulolytic enzyme; populations of total bacteria, protozoa and dominant cellulolytic bacteria; and concentrations of Cu in serum and liver increased linearly, but ruminal propionate percentage, ammonia-N concentration, α-amylase activity and populations of Prevotella ruminicola and Ruminobacter amylophilus decreased linearly. The results indicated that supplement of CS could be substituted with CCS and addition of CCS improved milk performance and nutrient digestion in dairy cows.
The low-frequency linearly polarised radio source population is largely unexplored. However, a renaissance in low-frequency polarimetry has been enabled by pathfinder and precursor instruments for the Square Kilometre Array. In this second paper from the POlarised GaLactic and Extragalactic All-Sky MWA Survey-the POlarised GLEAM Survey, or POGS-we present the results from our all-sky MWA Phase I Faraday Rotation Measure survey. Our survey covers nearly the entire Southern sky in the Declination range $-82^\circ$ to $+30^\circ$ at a resolution between around three and seven arcminutes (depending on Declination) using data in the frequency range 169−231 MHz. We have performed two targeted searches: the first covering 25 489 square degrees of sky, searching for extragalactic polarised sources; the second covering the entire sky South of Declination $+30^\circ$, searching for known pulsars. We detect a total of 517 sources with 200 MHz linearly polarised flux densities between 9.9 mJy and 1.7 Jy, of which 33 are known radio pulsars. All sources in our catalogues have Faraday rotation measures in the range $-328.07$ to $+279.62$ rad m−2. The Faraday rotation measures are broadly consistent with results from higher-frequency surveys, but with typically more than an order of magnitude improvement in the precision, highlighting the power of low-frequency polarisation surveys to accurately study Galactic and extragalactic magnetic fields. We discuss the properties of our extragalactic and known-pulsar source population, how the sky distribution relates to Galactic features, and identify a handful of new pulsar candidates among our nominally extragalactic source population.
Guanidinoacetic acid (GAA) can improve the growth performance of bulls. This study investigated the influences of GAA addition on growth, nutrient digestion, ruminal fermentation and serum metabolites in bulls. Forty-eight Angus bulls were randomly allocated to experimental treatments, that is, control, low-GAA (LGAA), medium-GAA (MGAA) and high-GAA (HGAA), with GAA supplementation at 0, 0.3, 0.6 and 0.9 g/kg DM, respectively. Bulls were fed a basal diet containing 500 g/kg DM concentrate and 500 g/kg DM roughage. The experimental period was 104 days, with 14 days for adaptation and 90 days for data collection. Bulls in the MGAA and HGAA groups had higher DM intake and average daily gain than bulls in the LGAA and control groups. The feed conversion ratio was lowest in MGAA and highest in the control. Bulls receiving 0.9 g/kg DM GAA addition had higher digestibility of DM, organic matter, NDF and ADF than bulls in other groups. The digestibility of CP was higher for HGAA than for LGAA and control. The ruminal pH was lower for MGAA, and the total volatile fatty acid concentration was greater for MGAA and HGAA than for the control. The acetate proportion and acetate-to-propionate ratio were lower for MGAA than for LGAA and control. The propionate proportion was higher for MGAA than for control. Bulls receiving GAA addition showed decreased ruminal ammonia N. Bulls in MGAA and HGAA had higher cellobiase, pectinase and protease activities and Butyrivibrio fibrisolvens, Prevotella ruminicola and Ruminobacter amylophilus populations than bulls in LGAA and control. However, the total protozoan population was lower for MGAA and HGAA than for LGAA and control. The total bacterial and Ruminococcus flavefaciens populations increased with GAA addition. The blood level of creatine was higher for HGAA, and the activity of l-arginine glycine amidine transferase was lower for MGAA and HGAA, than for control. The blood activity of guanidine acetate N-methyltransferase and the level of folate decreased in the GAA addition groups. The results indicated that dietary addition of 0.6 or 0.9 g/kg DM GAA improved growth performance, nutrient digestion and ruminal fermentation in bulls.
Human-computer hybrid teams can meet challenges in designing complex engineered systems. However, the understanding of interaction in the hybrid teams is lacking. We review the literature and identify four key attributes to construct design research platforms that support multi-phase design, hybrid teams, multiple design scenarios, and data logging. Then, we introduce a platform for unmanned aerial vehicle (UAV) design embodying these attributes. With the platform, experiments can be conducted to study how designers and intelligent computational agents interact, support, and impact each other.
Lameness is a very important disorder of periparturient dairy cows with implications on milk production and composition as well as with consequences on reproductive performance. The aetiology of lameness is not clear although there have been various hypotheses suggested over the years. The objective of this study was to metabotype the urine of dairy cows prior to, during and after the onset of lameness by evaluating at weeks −8, −4 pre-calving, the week of lameness diagnosis, and +4 and +8 weeks post-calving. We used a metabolomics approach to analyse urine samples collected from dairy cows around calving (6 cows with lameness v. 20 healthy control cows). A total of 153 metabolites were identified and quantified using an in-house MS library and classified into 6 groups including: 11 amino acids (AAs), 39 acylcarnitines (ACs), 3 biogenic amines (BAs), 84 glycerophospholipids, 15 sphingolipids and hexose. A total of 23, 36, 40, 23 and 49 metabolites were observed to be significantly different between the lame and healthy cows at −8 and −4 weeks pre-calving, week of lameness diagnosis as well as at +4 and +8 weeks post-calving, respectively. It should be noted that most of the identified metabolites were elevated; however, a few of them were also lower in lame cows. Overall, ACs and glycerophospholipids, specifically phosphatidylcholines (PCs), were the metabolite groups displaying the strongest differences in the urine of pre-lame and lame cows. Lysophosphatidylcholines (LysoPCs), although to a lesser extent than PCs, were altered at all time points. Alterations in urinary AA concentrations were also observed during the current study for four time points. During the pre-calving period, there was an observed elevation of arginine (−8 week), tyrosine (−8 week) and aspartate (−4 week), as well as a depression of urinary glutamate (−4 weeks). In the current study, it was additionally observed that concentrations of several sphingomyelins and one BA were altered in pre-lame and lame cows. Symmetric dimethylarginine was elevated at both −8 weeks pre-calving and the week of lameness diagnosis. Data showed that urinary fingerprinting might be a reliable methodology to be used in the future to differentiate lame cows from healthy ones.
Reducing stigma is a perennial target of mental health advocates, but effectively addressing stigma relies on the ability to correctly understand and accurately measure culture-specific and location-specific components of stigma and discrimination.
We developed two culture-sensitive measures that assess the core components of stigma. The 40-item Interpersonal Distance Scale (IDS) asks respondents about their willingness to establish four different types of relationships with individuals with 10 target conditions, including five mental health-related conditions and five comparison conditions. The 40-item Occupational Restrictiveness Scale (ORS) asks respondents how suitable it is for individuals with the 10 conditions to assume four different types of occupations. The scales – which take 15 min to complete – were administered as part of a 2013 survey in Ningxia Province, China to a representative sample of 2425 adult community members.
IDS and ORS differentiated the level of stigma between the 10 conditions. Of the total, 81% of respondents were unwilling to have interpersonal relationships with individuals with mental health-related conditions and 91% considered them unsuitable for various occupations. Substantial differences in attitudes about the five mental health-related conditions suggest that there is no community consensus about what constitutes a ‘mental illness’.
Selection of comparison conditions, types of social relationships, and types of occupations considered by the IDS and ORS make it possible to develop culture-sensitive and cohort-specific measures of interpersonal distance and occupational restrictiveness that can be used to compare the level and type of stigma associated with different conditions and to monitor changes in stigma over time.