Influence of Yb:YAG laser beam parameters on Haynes 188 weld fusion zone microstructure and mechanical properties

The weldability of 1.2 mm thick Haynes 188 alloy sheets by a disk Yb:YAG laser welding was examined. Butt joints were made, and the influence of parameters such as power, size, and shape of the spot, welding speed, and gas flow has been investigated. Based on an iconographic correlation approach, optimum process parameters were determined. Depending on the distribution of the power density (circular or annular), acceptable welds were obtained. Powers greater than 1700 W, welding speeds higher than 3.8 m mm1, and spot sizes between 160 and 320 lm were needed in the circular (small fiber) configuration. By comparison, the annular (large fiber) configuration required a power as high as 2500 W, and a welding speed less than 3.8 m min�1. The mechanical properties of the welds depended on their shape and microstructure, which in turn depended on the welding conditions. The content of carbides, the proportion of areas consisting of cellular and dendritic substructures, and the size of these substructures were used to explain the welded joint mechanical properties

A parametric study on the dynamic response of planar multibody systems with multiple clearance joints

A general methodology for dynamic modeling and analysis of multibody systems with multiple clearance joints is presented and discussed in this paper. The joint components that constitute a real joint are modeled as colliding bodies, being their behavior influenced by geometric and physical properties of the contacting surfaces. A continuous contact force model, based on the elastic Hertz theory together with a dissipative term, is used to evaluate the intra-joint contact forces. Furthermore, the incorporation of the friction phenomenon, based on the classical Coulomb’s friction law, is also discussed. The suitable contact-impact force models are embedded into the dynamics of multibody systems methodologies. An elementary mechanical system is used to demonstrate the accuracy and efficiency of the presented approach, and to discuss the main assumptions and procedures adopted. Different test scenarios are considered with the purpose of performing a parametric study for quantifying the influence of the clearance size, input crank speed and number of clearance joints on the dynamic response of multibody systems with multiple clearance joints. Additionally, the total computation time consumed in each simulation is evaluated in order to test the computational accuracy and efficiency of the presented approach. From the main results obtained in this study, it can be drawn that clearance size and the operating conditions play a crucial role in predicting accurately the dynamic responses of multibody systems.Fundação para a Ciência e a Tecnologia (FCT

On the contact detection for contact-impact analysis in multibody systems

One of the most important and complex parts of the simulation of multibody systems with contact-impact involves the detection of the precise instant of impact. In general, the periods of contact are very small and, therefore, the selection of the time step for the integration of the time derivatives of the state variables plays a crucial role in the dynamics of multibody systems. The conservative approach is to use very small time steps throughout the analysis. However, this solution is not efficient from the computational view point. When variable time step integration algorithms are used and the pre-impact dynamics does not involve high-frequencies the integration algorithms may use larger time steps and the contact between two surfaces may start with initial penetrations that are artificially high. This fact leads either to a stall of the integration algorithm or to contact forces that are physically impossible which, in turn, lead to post-impact dynamics that is unrelated to the physical problem. The main purpose of this work is to present a general and comprehensive approach to automatically adjust the time step, in variable time step integration algorithms, in the vicinity of contact of multibody systems. The proposed methodology ensures that for any impact in a multibody system the time step of the integration is such that any initial penetration is below any prescribed threshold. In the case of the start of contact, and after a time step is complete, the numerical error control of the selected integration algorithm is forced to handle the physical criteria to accept/reject time steps in equal terms with the numerical error control that it normally uses. The main features of this approach are the simplicity of its computational implementation, its good computational efficiency and its ability to deal with the transitions between non contact and contact situations in multibody dynamics. A demonstration case provides the results that support the discussion and show the validity of the proposed methodology.Fundação para a Ciência e a Tecnologia (FCT

Lack of association of rs3798220 with small apolipoprotein(a) isoforms and high lipoprotein(a) levels in East and Southeast Asians

OBJECTIVE : The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS : We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS : The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION : Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.http://www.elsevier.com/locate/atherosclerosis2016-10-31hb2016Chemical Patholog

Distinct gut virome profile of pregnant women with type 1 diabetes in the ENDIA study

Background:The importance of gut bacteria in human physiology, immune regulation, and disease pathogenesis is well established. In contrast, the composition and dynamics of the gut virome are largely unknown; particularly lacking are studies in pregnancy. We used comprehensive virome capture sequencing to characterize the gut virome of pregnant women with and without type 1 diabetes (T1D), longitudinally followed in the Environmental Determinants of Islet Autoimmunity study. Methods:In total, 61 pregnant women (35 with T1D and 26 without) from Australia were examined. Nucleic acid was extracted from serial fecal specimens obtained at prenatal visits, and viral genomes were sequenced by virome capture enrichment. The frequency, richness, and abundance of viruses were compared between women with and without T1D. Results:Two viruses were more prevalent in pregnant women with T1D: picobirnaviruses (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.0-17.1; P = .046) and tobamoviruses (OR, 3.2; 95% CI, 1.1-9.3; P = .037). The abundance of 77 viruses significantly differed between the 2 maternal groups (≥2-fold difference; P < .02), including 8 Enterovirus B types present at a higher abundance in women with T1D. Conclusions:These findings provide novel insight into the composition of the gut virome during pregnancy and demonstrate a distinct profile of viruses in women with T1D.Ki Wook Kim, Digby W. Allen ... Simon C. Barry ... Lynne C Giles ... Megan A S Penno ... Rebecca L Thomson ... et al

Quantum Dots and Wires to improve Enzymes-Based Electrochemical Bio- sensing

An investigation on nano-structured electrodes to detect different metabolites is proposed in this paper. Three different metabolites are considered: glucose, lactate, and cholesterol. The direct detection of hydrogen peroxide is also considered since it does not involve any enzyme. The metabolites and the peroxide were detected by using screen-printed electrodes modified by using multi-walled carbon nanotubes. In all cases, improvements of orders of magnitude were registered both on detection sensitivity and on detection limit. A close comparison with data recently published in literature has shown the existence of an inverse linear correlation between detection sensitivity and detection limit when sensor performances improve due to nano- structured materials. This inverse linear relationship seems to be a general law as it is here demonstrated for all the considered detections on glucose, lactate, cholesterol, and hydrogen peroxide

The satisfactory growth and development at 2 years of age of the INTERGROWTH-21st Fetal Growth Standards cohort support its appropriateness for constructing international standards.

BACKGROUND: The World Health Organization recommends that human growth should be monitored with the use of international standards. However, in obstetric practice, we continue to monitor fetal growth using numerous local charts or equations that are based on different populations for each body structure. Consistent with World Health Organization recommendations, the INTERGROWTH-21st Project has produced the first set of international standards to date pregnancies; to monitor fetal growth, estimated fetal weight, Doppler measures, and brain structures; to measure uterine growth, maternal nutrition, newborn infant size, and body composition; and to assess the postnatal growth of preterm babies. All these standards are based on the same healthy pregnancy cohort. Recognizing the importance of demonstrating that, postnatally, this cohort still adhered to the World Health Organization prescriptive approach, we followed their growth and development to the key milestone of 2 years of age. OBJECTIVE: The purpose of this study was to determine whether the babies in the INTERGROWTH-21st Project maintained optimal growth and development in childhood. STUDY DESIGN: In the Infant Follow-up Study of the INTERGROWTH-21st Project, we evaluated postnatal growth, nutrition, morbidity, and motor development up to 2 years of age in the children who contributed data to the construction of the international fetal growth, newborn infant size and body composition at birth, and preterm postnatal growth standards. Clinical care, feeding practices, anthropometric measures, and assessment of morbidity were standardized across study sites and documented at 1 and 2 years of age. Weight, length, and head circumference age- and sex-specific z-scores and percentiles and motor development milestones were estimated with the use of the World Health Organization Child Growth Standards and World Health Organization milestone distributions, respectively. For the preterm infants, corrected age was used. Variance components analysis was used to estimate the percentage variability among individuals within a study site compared with that among study sites. RESULTS: There were 3711 eligible singleton live births; 3042 children (82%) were evaluated at 2 years of age. There were no substantive differences between the included group and the lost-to-follow up group. Infant mortality rate was 3 per 1000; neonatal mortality rate was 1.6 per 1000. At the 2-year visit, the children included in the INTERGROWTH-21st Fetal Growth Standards were at the 49th percentile for length, 50th percentile for head circumference, and 58th percentile for weight of the World Health Organization Child Growth Standards. Similar results were seen for the preterm subgroup that was included in the INTERGROWTH-21st Preterm Postnatal Growth Standards. The cohort overlapped between the 3rd and 97th percentiles of the World Health Organization motor development milestones. We estimated that the variance among study sites explains only 5.5% of the total variability in the length of the children between birth and 2 years of age, although the variance among individuals within a study site explains 42.9% (ie, 8 times the amount explained by the variation among sites). An increase of 8.9 cm in adult height over mean parental height is estimated to occur in the cohort from low-middle income countries, provided that children continue to have adequate health, environmental, and nutritional conditions. CONCLUSION: The cohort enrolled in the INTERGROWTH-21st standards remained healthy with adequate growth and motor development up to 2 years of age, which supports its appropriateness for the construction of international fetal and preterm postnatal growth standards

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanismof anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.Therapeutic cell differentiatio