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Getting numbers is easy; getting numbers you can trust is hard. This practical guide by experimentation leaders at Google, LinkedIn, and Microsoft will teach you how to accelerate innovation using trustworthy online controlled experiments, or A/B tests. Based on practical experiences at companies that each run more than 20,000 controlled experiments a year, the authors share examples, pitfalls, and advice for students and industry professionals getting started with experiments, plus deeper dives into advanced topics for practitioners who want to improve the way they make data-driven decisions.Learn how toUse the scientific method to evaluate hypotheses using controlled experiments Define key metrics and ideally an Overall Evaluation CriterionTest for trustworthiness of the results and alert experimenters to violated assumptionsBuild a scalable platform that lowers the marginal cost of experiments close to zeroAvoid pitfalls like carryover effects and Twyman's lawUnderstand how statistical issues play out in practice.
In this chapter, we discuss romantic relationship maintenance in the context of self-expansion. Overall, we review the self-expansion model and its accompanying empirical literature over the past 30 years, and consider some implications and future directions. Specifically, we begin by conceptualizing relationship maintenance, describing the self-expansion model (including both of its key principles: motivation to expand one's abilities to accomplish goals and including close others in the self), and covering some of the foundational work conducted with couples (e.g., self–other overlap and relational benefits of shared exciting activities). We then review research showing that relationship maintenance and self-expansion are positively related, and discuss potential mechanisms and theoretical underpinnings. We next explore more recent research on individual self-expansion and its implications for the maintenance of close relationships. Throughout the chapter, we provide illustrative examples of how self-expansion is associated with relationship characteristics, behaviors, maintenance, and outcomes. These examples will hopefully allow readers to better understand the concepts, theories, and empirical findings, and also allow utilization of this knowledge in real-life applications. Finally, we end with a summary and discussion of future directions for self-expansion and relationship researchers.
This study seeks to identify healthcare utilization patterns following symptomatic respiratory tract infections (RTIs) and the variables that may influence these patterns.
RTIs are responsible for the bulk of the primary healthcare burden worldwide. Yet, the use of health services for RTIs displays great discrepancies between populations. This research examines the influence of social demographics, economic factors, and accessibility on healthcare utilization following RTIs.
Structured interviews were administered by trained physicians at the households of informants selected by cluster randomization. Descriptive and multivariate binary logistic regression analysis was performed to assess healthcare utilization and associated independent variables.
A total of 60 678 informants completed the interviews. Of the 2.9% informants exhibiting upper RTIs, 69.5–73.9% sought clinical care. Healthcare utilization rates for common cold, influenza, nine acute upper RTIs, and overall RTIs demonstrate statistically significant associations with the variables of age, type of residence, employment, medical insurance, annual food expenditure, distance to medical facilities, and others. The odds ratios for healthcare utilization rates varied substantially, ranging from 0.026 to 9.364. More than 69% of informants with RTIs sought clinical interventions. These findings signify a marked issue with the large amount of healthcare for self-limited RTIs.
Mechanical fracture of electrodes will occur during lithiation caused by large volume changes, which leads to the capacity loss of the lithium-ion battery. Herein, we present a new analytical model to investigate the effect of creep deformation on stress relaxation and fracture of the lithiated tin (Sn) electrode under the galvanostatic and potentiostatic operation. Interestingly, it is found that the presence of creep can improve fracture resistance and toughness of the Sn electrode. In addition, the surface effect has the capacity to weaken the creep deformation effectively. And the different size of the Sn electrode shows different effects for creep deformation. This conclusion explains the difference in charging conditions, and the mechanism of stress change inside the electrode is also different. Deeply, the base on our model, the stress strength factor, and critical size of the electrode have been evaluated under galvanostatic and potentiostatic operation with creep deformation effects. Finally, the safety area during lithiation is established to determine the critical size of the Sn electrode. And the presence of creep deformation may significantly increase critical dimensions of the electrode. These results will provide a valuable basis to design the durable electrodes.
Cellular senescence, a driver of aging and age-related diseases, is a stable state found in metabolically active cells characterized by irreversible cell growth arrest and dramatic changes in metabolism, gene expression and secretome profile. Endogenous regeneration efficacy of mesenchymal stem cells (MSCs) could be attenuated due to senescence. MSCs can be modulated by not only biochemical signals but also by physical cues such as substrate topography. To provide a cell culture substrate that can prevent MSC senescence over an extended period of in vitro cultivation, here, the cell- and immunocompatible poly(ether imide) (PEI) substrate was used. Two distinct levels of roughness were created on the bottom surfaces of PEI inserts via injection molding: Low-R (similar to the thickness of attached single MSC, Rq: 3.9 ± 0.2 µm) and High-R (larger than single MSC thickness. Rq: 22.7 ± 0.8 µm). Cell expansion, lysosomal enzymatic activity, apoptosis and paracrine effects of senescent MSCs were examined by cell counting, detection of senescence-associated β-galactosidase (SA β-gal), Caspase 3/7, and CFSE labeling. MSCs showed high cell viability and similar spindle-shaped morphology on all investigated surfaces. Cells on Low-R presented the highest expansion (80000 ± 1805 cells), as compared to cells on smooth PEI and High-R. The low apoptosis level (0.08 vs 0.12 from smooth PEI) and senescence ratio (35% vs. 54% from smooth PEI) were observed in MSCs cultured on Low-R. The secretome from Low-R effectively prevents senescence and supports the proliferation of neighboring cells (1.5-fold faster) as compared to the smooth PEI secretome. In summary, the Low-R PEI provided a superior surface environment for MSCs, which promoted proliferation, inhibited apoptosis and senescence, and effectively influenced the proliferation of neighboring cells via their paracrine effect. Such microroughness can be considered as a key parameter for improving the therapeutic potential of endogenous regeneration, anti-organismal aging and anti-age-related pathologies via directly promoting cell growth and modulating paracrine effects of the senescence associated secretome.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
To investigate the hypothesis that folic acid supplementation and dietary folate intake before conception and during pregnancy reduce the risk of small for gestational age (SGA) and to examine the joint effect of folic acid supplementation and dietary folate intake on the risk of SGA.
Participants were interviewed by trained study interviewers using a standardized and structured questionnaire. Information on birth outcomes and maternal complications was abstracted from medical records and dietary information was collected via a semi-quantitative FFQ before conception and during pregnancy.
A birth cohort data analysis using the 2010–2012 Gansu Provincial Maternity and Child Care Hospital.
Women (n 8758) and their children enrolled in the study.
Folic acid supplementation was associated with a reduced risk of SGA (OR = 0·72, 95 % CI 0·60, 0·86), with the reduced risk seen mainly for SGA at ≥37 weeks of gestational age (OR = 0·70, 95 % CI 0·58, 0·85) and nulliparous SGA (OR = 0·67, 95 % CI 0·54, 0·84). There was no significant association between dietary folate intake and SGA risk.
Our study suggested that folic acid supplementation was associated with a reduced risk of SGA and the risk varied by preterm status and parity.
Distinguishing between hypertrophic cardiomyopathy and other causes ofleft ventricular hypertrophy can be difficult in children. We hypothesised that cardiac MRI T1 mapping could improve diagnosis of paediatric hypertrophic cardiomyopathy and that measures of myocardial function would correlate with T1 times and extracellular volume fraction.
Thirty patients with hypertrophic cardiomyopathy completed MRI with tissue tagging, T1-mapping, and late gadolinium enhancement. Left ventricular circumferential strain was calculated from tagged images. T1, partition coefficient, and synthetic extracellular volume were measured at base, mid, apex, and thickest area of myocardial hypertrophy. MRI measures compared to cohort of 19 healthy children and young adults. Mann–Whitney U, Spearman’s rho, and multivariable logistic regression were used for statistical analysis.
Hypertrophic cardiomyopathy patients had increased left ventricular ejection fraction and indexed mass. Hypertrophic cardiomyopathy patients had decreased global strain and increased native T1 (−14.3% interquartile range [−16.0, −12.1] versus −17.3% [−19.0, −15.7], p < 0.001 and 1015 ms [991, 1026] versus 990 ms [972, 1001], p = 0.019). Partition coefficient and synthetic extracellular volume were not increased in hypertrophic cardiomyopathy. Global native T1 correlated inversely with ejection fraction (ρ = −0.63, p = 0.002) and directly with global strain (ρ = 0.51, p = 0.019). A logistic regression model using ejection fraction and native T1 distinguished between hypertrophic cardiomyopathy and control with an area under the receiver operating characteristic curve of 0.91.
In this cohort of paediatric hypertrophic cardiomyopathy, strain was decreased and native T1 was increased compared with controls. Native T1 correlated with both ejection fraction and strain, and a model using native T1 and ejection fraction differentiated patients with and without hypertrophic cardiomyopathy.
Laboratory experiments have shown that thermal gradients in silicate melts can lead to isotopic fractionation; this is known as the Richter effect. However, it is perplexing that the Richter effect has not been documented in natural samples as thermal gradients commonly exist within natural igneous systems. To resolve this discrepancy, theoretical analysis and calculations were undertaken. We found that the Richter effect, commonly seen in experiments with wholly molten silicates, cannot be applied to natural systems because natural igneous samples are more likely to be formed out of partially molten magma and the presence of minerals adds complexity to the behaviour of the isotope. In this study, we consider two related diffusion-rate kinetic isotope effects that originate from chemical diffusion, which are absent from experiments with wholly molten samples. We performed detailed calculations for magnesium isotopes, and the results indicated that the Richter effect for magnesium isotopes is buffered by kinetic isotope effects and the total value of magnesium isotope fractionation can be zero or even undetectable. Our study provides a new understanding of isotopic behaviour during the processes of cooling and solidification in natural magmatic systems.
We present a new low-cost, high-throughput method for converting many types of organic carbon samples into graphite for radiocarbon (14C) measurements by accelerator mass spectrometry (AMS). The method combines sample combustion and reduction to graphite into a single procedure. In the Single Step method, solid samples are placed directly into Pyrex containing zinc, titanium hydride and iron catalyst. The tube is evacuated, flame sealed, and placed in a muffle furnace for 7 hr. A variety of organic samples have been tested including oxalic acid, sucrose, wood, peat, collagen, humic acid, and contamination swipe samples. The method significantly reduces the time required to produce a graphite sample for 14C measurement, with analytical precision and accuracy approaching that of traditional two-step combustion and hydrogen reduction methods. The details and applicability of the method are presented.
In this paper, we focus on the configuration design of a reconfigurable robot that merges the functions of wheels, tracks, and legs together. A deformable rim is utilized to make the robot wheel reconfigurable to change its locomotion mode. Three rules of configuration design to achieve reconfiguration between different modes are proposed: (1) in wheel mode, the track wheel set should be hidden inside the wheel rim; (2) in track/leg mode, the folded wheel rim should be hidden inside the caterpillar loop; (3) the circumference of the wheel rim in wheel mode should be equal to the length of the track ring in track mode. According to these rules, the configuration of the deformable rim, track wheel set, and telescopic spoke are analyzed and designed. A prototype of the reconfigurable wheel is fabricated by three-dimensional printing, and its functions of locomotion in different modes, the switch between different modes, and its load-bearing ability are tested, verifying the effectiveness of the configuration design. Furthermore, a prototype of the reconfigurable robot is manufactured by computerized numerical control (CNC) machining to verify the structural design of the reconfigurable wheel. Compared to traditional hybrid robots with separate wheels, tracks, and legs, this reconfigurable design lends the multimodal robot both excellent terrain adaptability and a compact structure; thus, it can be widely used as a universal mobile platform in search and rescue missions and explosive object disposal missions.
The aim of this study is to explore the influence of tea consumption on diabetes mellitus in Chinese population. This multicenter, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12,017 subjects aged 20–70. Sociodemographic and general information were collected by standardized questionnaire. Standard procedure was used to measure anthropometric characteristics and obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10,825 participants were included, and multiple logistic models and interaction effect analysis were applied for assessing the association between tea-drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted odds ratios for newly-diagnosed diabetes were 0.80(0.67, 0.97), 0.88(0.71, 1.09) and 0.86(0.67, 1.11) for daily tea-drinkers, occasional tea-drinkers and seldom tea-drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in female by 32%, elderly (>45y) by 24% and obese (BMI>30kg/m2) by 34%. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45% [OR: 0.55 (0.42, 0.72), P < 0.01]. The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of T2DM.
The seminiferous tubule (ST) is the location of spermatogenesis, where mature spermatozoa are produced with the assistance of Sertoli cells. The role of extracellular vesicles in the direct communication between Sertoli-germ cells in the ST is still not fully understood. In this study, we reported multivesicular bodies (MVBs) and their source of CD63-enriched exosomes by light and ultrastructure microscopy during the reproductive phases of turtles. Strong CD63 immunopositivity was detected at the basal region in the early and luminal regions of the ST during late spermatogenesis by immunohistochemistry (IHC), immunofluorescence (IF), and western blot (WB) analysis. Labeling of CD63 was detected in the Sertoli cell cytoplasmic processes that surround the developing germ cells during early spermatogenesis and in the lumen of the ST with elongated spermatids during late spermatogenesis. Furthermore, ultrastructure analysis confirmed the existence of numerous MVBs in the Sertoli cell prolongations that surround the round and primary spermatogonia during acrosome biogenesis and with the embedded heads of spermatids in the cytoplasm of Sertoli cells. Additionally, in spermatids, Chrysanthemum flower centers (CFCs) generated isolated membranes involved in MVBs and autophagosome formation, and their fusion to form amphiosomes was also observed. Additionally, autophagy inhibition by 3-methyladenine (after 24 h) increased CD63 protein signals during late spermatogenesis, as detected by IF and WB. Collectively, our study found MVBs and CD63 rich exosomes within the Sertoli cells and their response to autophagy inhibition in the ST during the spermatogenesis in the turtle.
Chinese conservatism is often reduced to a cultural movement the main concern of which is the preservation of traditional culture. This article proposes a new framework with which to analyze modern Chinese conservatism. It identifies late Qing culturalist nationalism, which incorporates traditional culture into concrete political reforms inspired by modern Western politics, as the origin of conservatism in the Republican era. Conservatism in this period was a reaction against New Culture activists’ denial of the political utility of this culturalist nationalism and constituted a response to World War I, leading some to question the merits of Western civilization. As a result, tradition no longer unitarily evoked the cultural elements corresponding to modern Western politics. Adopting a typological approach in order to distinguish different types of conservatism by differentiating various political implications of traditional culture, it divides the Chinese conservatism of the Republican era into four typologies: liberal conservatism, antimodern conservatism, philosophical conservatism, and authoritarian conservatism.
Subject–verb (SV) agreement helps listeners interpret the number condition of ambiguous nouns (The sheep is/are fat), yet it remains unclear whether young children use agreement to comprehend newly encountered nouns. Preschoolers and adults completed a forced choice task where sentences contained singular vs. plural copulas (Where is/are the [novel noun(s)]?). Novel nouns were either morphologically unambiguous (tup/tups) or ambiguous (/geks/ = singular: gex / plural: gecks). Preschoolers (and some adults) ignored the singular copula, interpreting /ks/-final words as plural, raising questions about the role of SV agreement in learners’ sentence comprehension and the status of is in Australian English.
Establishment of cellular polarity is one of the key events during oocyte maturation. Inscuteable (Insc) has been identified as a key regulator of cell polarity during asymmetric division in Drosophila. However, the function of its evolutionarily conserved mammalian homologue, mInscuteable (mInsc), in mouse meiotic maturation is not clear. In this study, we investigated the roles of mInsc in mouse oocyte maturation. mInsc was detected at all stages of oocyte maturation. The protein level of mInsc was slightly higher at the germinal vesicle breakdown (GVBD) stage and remained constant during mouse oocyte maturation. The subcellular localization of mInsc overlapped with spindle microtubules. Disruption of microtubules and microfilaments caused changes in the localization of mInsc. Depletion or overexpression of mInsc significantly decreased the maturation rates of mouse oocytes. Depletion of mInsc significantly affected asymmetric division, spindle assembly, alignments of chromosomes and actin cap formation. Taken together, our results demonstrated that mInsc regulates meiotic spindle organization during mouse meiotic maturation.
This study explored how internet queries vary in facilitating monitoring of pertussis, and the effects of sociodemographic characteristics on such variation by city in Shandong province, China. We collected weekly pertussis notifications, Baidu Index (BI) data and yearly sociodemographic data at the city level between 1 January 2009 and 31 December 2017. Spearman's correlation was performed for temporal risk indices, generalised linear models and regression tree models were developed to identify the hierarchical effects and the threshold between sociodemographic factors and internet query data with pertussis surveillance. The BI was correlated with pertussis notifications, with a strongly spatial variation among cities in temporal risk indices (composite temporal risk metric (CTRM) range: 0.59–1.24). The percentage of urban population (relative risk (RR): 1.05, 95% confidence interval (CI) 1.03–1.07), the proportion of highly educated population (RR: 1.27, 95% CI 1.16–1.39) and the internet access rate (RR: 1.04, 95% CI 1.02–1.05) were correlated with CTRM. Higher RRs in the three identified sociodemographic factors were associated with higher stratified CTRM. The percentage of highly educated population was the most important determinant in the BI with pertussis surveillance. The findings may lead to spatially-specific criteria to inform development of an early warning system of pertussis infections using internet query data.
The work described in this research communication aimed to investigate whether rumen-protected methionine (Met) supplementation during the periparturient period would affect the expression of galectins in blood-derived neutrophils, and secretion of galectins, IL (interleukin)-1β, IL-6, myeloperoxidase (MPO), and glucose in plasma. Because supplementation of rumen-protected Met would alleviate inflammation and oxidative stress during the peripartal period, we hypothesized that enhancing Met supply would benefit the innate immune response at least in part by altering the expression of galectin genes associated with neutrophil activity and inflammation. Galectins (Gal) have an immuno-modulating effect acting like cell-surface receptors whose activation often results in signaling cascades stimulating cells such as neutrophils. This study revealed an association between Met supplementation and galectin expression and secretion. This implies that galectin expression and secretion can be modulated by Met supplementation. Further studies are needed to evaluate the regulation of galectin gene expression for therapeutic and dietary intervention in the peripartal cow.
Heading errors caused by gyroscope drift affect the positioning precision of pedestrian dead reckoning, and these errors are even greater for smartphone-based reckoning. In this study, an optimised improved heuristic drift elimination (O-iHDE) method is proposed to correct the heading errors on a smartphone gyroscope. Based on an analysis of the improved heuristic drift elimination (iHDE) and enhanced improved heuristic drift elimination (E-iHDE) algorithms, the quaternion method is used to update the attitude and angle threshold judgement conditions, and a method for correcting the quaternion is added to eliminate the heading errors caused by random gyro errors. The analysis of multiple sets of experiments shows that the new method improves the ability to discern and correct the walking route, and the heading accuracy is improved by more than 90%, which extends the effective operation time of pedestrian dead reckoning positioning based on the step-by-step system.