794 research outputs found
A Work Approach to Determine Vickers Indentation Fracture Toughness
No full textAccording to the comparison of Vickers microindentation tests and Vickers macroindentation tests on several brittle materials, it is found that the ratio of hardness (H) to elastic modulus (E) is sensitive to well-developed radial cracks, but the ratio of unloading work (W(u)) to total loading work (W(t)) is not. Based on this finding together with the approximate linear relationship between the ratio of H to reduced modulus (E(r)) and W(u)/W(t), a new approach taking W(u)/W(t) instead of H/E as the input parameter to determine Vickers indentation fracture toughness is proposed. For this proposed approach, all input parameters can be obtained in one single instrumented indentation test for fracture toughness, thus the test procedure can be simplified significantly. The formula of the newly proposed approach is calibrated by the macroindentation tests on several brittle materials. The validity of the new approach is investigated by comparing its estimation with the old one's
Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet
No full textIncreasing evidence suggests a role for prenatal environment in the onset of cardiovascular and metabolic disease in later life. In the rat, undernutrition in utero and a postnatal high-fat diet gives rise to a phenotype similar to the metabolic syndrome. As endothelial dysfunction is a feature of both CVD and the metabolic syndrome we investigated the impact of maternal undernutrition and/or postnatal high-fat on endothelial function. Virgin Wistar rats were mated and randomly assigned to groups to receive food either ad libitum (control) or at 30 % of ad libitum intake throughout gestation. At postnatal day 250, a cohort from each group was challenged with a high-fat diet (D12451, 45 % energy from fat; Research Diets, Inc., New Brunswick, NJ, USA) for the remainder of the study. At 1 year of age, small mesenteric arteries were dissected and mounted on a wire myograph and responses to phenylephrine, endothelin, acetylcholine, leptin and sodium nitroprusside assessed. Vasoconstriction to endothelin was significantly enhanced in all groups compared with controls (-log effective concentration equal to 50 % of the maximal response (pEC50); P < 0.001). Endothelium-dependent vasodilatation to acetylcholine was significantly blunted in all groups compared with controls (% maximum response; P < 0.01), while dilatation to leptin and sodium nitroprusside was similar in all groups. These data demonstrate that both maternal undernutrition and postnatal high fat lead to vascular alterations and suggest that maternal undernutrition alone is at least as detrimental to offspring endothelial function as a long-term exposure to a high-fat diet in the offspring<br/
Leptin reversal of the metabolic phenotype: evidence for the role of developmental plasticity in the development of the metabolic syndrome
No full textEvents in early life are associated with changes in the risk of disease in later life. There is increasing evidence that these associations are mediated by permanent transcriptional changes in metabolic pathways, in some cases linked to epigenetic alterations. We have proposed that this phenomenon of 'developmental induction' is not a manifestation of pathophysiological processes but rather represents the consequence of developmental decisions made during fetal and early postnatal life to maximize subsequent fitness. However, this fitness advantage is lost if the early and later environments are mismatched. Rats undernourished in utero by maternal underfeeding develop features of the metabolic syndrome, especially if fed on a high-fat diet, but transient neonatal treatment with leptin reverses induction of this adverse metabolic phenotype. This observation demonstrates that developmental programming is reversible and provides strong support for the match-mismatch or predictive model for the origins of developmental programming
Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat
No full textBackgroundWhile prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring.MethodsPregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses.ResultsWe report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal's nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring's nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations.ConclusionsThese observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis
Tissue-specific 5' heterogeneity of PPARa transcripts and their differential regulation by leptin
No full textThe genes encoding nuclear receptors comprise multiple 5'untranslated exons, which give rise to several transcripts encoding the same protein, allowing tissue-specific regulation of expression. Both human and mouse peroxisome proliferator activated receptor (PPAR) ? genes have multiple promoters, although their function is unknown. Here we have characterised the rat PPAR? promoter region and have identified three alternative PPAR? transcripts, which have different transcription start sites owing to the utilisation of distinct first exons. Moreover these alternative PPAR? transcripts were differentially expressed between adipose tissue and liver. We show that while the major adipose (P1) and liver (P2) transcripts were both induced by dexamethasone, they were differentially regulated by the PPAR? agonist, clofibric acid, and leptin. Leptin had no effect on the adipose-specific P1 transcript, but induced liver-specific P2 promoter activity via a STAT3/Sp1 mechanism. Moreover in Wistar rats, leptin treatment between postnatal day 3-13 led to an increase in P2 but not P1 transcription in adipose tissue which was sustained into adulthood. This suggests that the expression of the alternative PPAR? transcripts are in part programmed by early life exposure to leptin leading to persistent change in adipose tissue fatty acid metabolism through specific activation of a quiescent PPAR? promoter. Such complexity in the regulation of PPAR? may allow the expression of PPAR? to be finely regulated in response to environmental factors
Metabolic plasticity during mammalian development is directionally dependent on early nutritional status
No full textDevelopmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status in utero. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenis
sj-pdf-1-ajs-10.1177_03635465211049219 – Supplemental material for Obesity Impairs Enthesis Healing After Rotator Cuff Repair in a Rat Model
No full textSupplemental material, sj-pdf-1-ajs-10.1177_03635465211049219 for Obesity Impairs Enthesis Healing After Rotator Cuff Repair in a Rat Model by Scott M. Bolam, Young-Eun Park, Subhajit Konar, Karen E. Callon, Josh Workman, A. Paul Monk, Brendan Coleman, Jillian Cornish, Mark H. Vickers, Jacob T. Munro and David S. Musson in The American Journal of Sports Medicine</p
Automatic Method for Vickers Hardness Estimation by Image Processing
No full textHardness is one of the most important mechanical properties of materials, since it is used to estimate their quality and to determine their suitability for a particular application. One method of determining quality is the Vickers hardness test, in which the resistance to plastic deformation at the surface of the material is measured after applying force with an indenter. The hardness is measured from the sample image, which is a tedious, time-consuming, and prone to human error procedure. Therefore, in this work, a new automatic method based on image processing techniques is proposed, allowing for obtaining results quickly and more accurately even with high irregularities in the indentation mark. For the development and validation of the method, a set of microscopy images of samples indented with applied forces of 5N and 10N on AISI D2 steel with and without quenching, tempering heat treatment and samples coated with titanium niobium nitride (TiNbN) was used. The proposed method was implemented as a plugin of the ImageJ program, allowing for obtaining reproducible Vickers hardness results in an average time of 2.05 seconds with an accuracy of 98.3% and a maximum error of 4.5% with respect to the values obtained manually, used as a golden standard
Behaviour of ODS 12Cr steel under thermal treatment at micro and macro level: A positron annihilation and Vickers hardness study
No full textThe behaviour of ODS 12Cr steel under thermal treatment is studied in this report at micro and macro level. ODS 12Cr steel is always in the ferrite phase and has a melting point at 1500 ºC. Before studying,the retrieved samples were metallographically prepared in four steps: mounting, grinding, mechanically polishing and electrolytically polishing. A measurement was done to analyse the effect of electrolytically polishing on bulk S and W parameters. This showed that mechanically polishing with 0.04 μm alumina particles has the same effect as electrolytically polishing. Next, the alloy was studied with three different measurement techniques: positron annihilation Doppler broadening spectroscopy, Vickers hardness test and positron lifetime measurements. Before these measurements the samples were annealed at selected temperatures for 10 minutes and naturally cooled.The Doppler broadening spectroscopy was done with the Variable Energy Positron beam (VEP) at the Reactor Institute Delft (RID). With this set-up the S and W parameter were measured at different im-plantation energies and converging bulk values of them were determined. The results were fitted with VEPFIT. This measurement was done in the as received state and after annealing from 200 ºC up to1300 ºC in steps of 100 ºC. The Vickers hardness test was done with a load of 0.3 kgf and in the same temperature range as the VEP measurements but with steps of 200 ºC. A lifetime spectrum was measured in the as received state with two sample sandwiching a 22Na source packed with kapton. The average lifetime was determined by fitting the spectrum with LT 9.2. This measurement was repeatedafter annealing for 10 minutes from 200 ºC up to 700 ºC in steps of 100 ºC.The three different measurement techniques show corresponding results. Up to annealing temperatures of 1000 ºC the results stay constant. The bulk S and W parameters are respectively 0.475 and 0.078.The Vickers hardness stays at 395 HV and is comparable to literature values. The average lifetime is approximately 208 ps, which corresponds with defects with sizes comparable to or at least larger thanthat of divacancies. At this temperatures most thermal vacancies are trapped by the nano-oxide particles and are not able to liberate themselves which causes the constant results. At higher temperatures (larger than 1100 ºC) the thermal vacancy concentration increases and the vacancies gain enough energy to be liberated. This causes, in combination with oxide particles clustering, more defects in the material and explains the increasing bulk S value for temperatures up from 1100 ºC. The high bulk S values, compared with an iron alloy with less chromium, can also originate from clustering of chromium atoms. The surface S parameters are also increased in this temperature domain due to the formation of an oxide layer which can be seen with the naked-eye. Finally, the hardness value decreases to 374 HV after annealing at 1200 ºC which is a significant decrease and indicates that the pinning of the nano-particles decreases, resulting in grains growing easier.Applied Physic
Decoding the regulatory landscape of psychiatric and alcohol use disorders
No full textEpidemiological research has shown that psychiatric and substance use disorders are
multimorbid conditions that are characterized by significant and complex genetic etiology. While
genome-wide association studies (GWAS) have identified thousands of single-nucleotide
polymorphisms (SNPs) associated with psychiatric and substance use disorders, the mechanisms
by which these SNPs contribute to the observed multimorbidities remain largely unknown. This
is because more than 90% of these SNPs reside in the non-coding regions of the genome, which
makes interpretation of their functional impacts challenging. To address this challenge, I integrated
different distinct levels of biological information (i.e. SNPs, gene expression, spatial genome
organization and protein-protein interactions) to identify tissue-specific regulatory impacts of
psychiatric and alcohol dependence-associated SNPs on biological pathways. This enabled me to
determine potential regulatory mechanisms that can explain the underlying multimorbidity among
these phenotypes. First, I have analysed 2,893 GWAS SNPs associated with attention-deficit
hyperactivity disorder (ADHD), anxiety, bipolar disorder (BD), unipolar depression (UD),
schizophrenia and cognitive functioning to identify the genes and biological pathways they control.
The analysis revealed 33 genes and 62 pathways that were commonly affected by tissue-specific
regulatory interactions associated with all six phenotypes. Next, I have identified the tissue-specific
regulatory landscape of alcohol dependence (AD). Of the AD regulatory interactions I identified,
42% were associated with genes encoding alcohol dehydrogenase (ADH) and aldehyde
dehydrogenase (ALDH) enzymes, and they were mostly linked to adipose and gastrointestinal
tissues. Further analyses of the global patterns of ADH and ALDH regulatory interactions
revealed ADH associations with AD-related traits and ALDH associations with psychiatric
disorders and cognition. Finally, I have identified the cortex-specific regulatory impacts of 344
SNPs associated with autism spectrum disorder, and showed that these SNPs were also linked to
other psychiatric disorders (e.g. schizophrenia, ADHD, BD). Subsequent protein-protein
interaction analysis revealed that these SNPs impact on immune pathways, fatty acid metabolism,
ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosomes in the fetal cortex. By
contrast in the adult cortex, they largely affect immune pathways. Collectively, these results
highlight potential regulatory mechanisms and key pathways underlying the development of
psychiatric and substance use disorders, and their observed multi/co-morbidities. This integrative
approach, in combination with clinical studies, will contribute to personalized mechanistic
understandings of these complex disorders
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