Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo.

In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken embryo-an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother or the placenta. Fertilized chicken eggs were exposed to normoxia (N; 21% O2) or hypoxia (H; 13.5%-14% O2) from the start of incubation (day 0) until day 19 (hatching, ≈day 21). Following hatching, all birds were maintained under normoxic conditions until ≈6 months of adulthood. Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetrical growth restriction (body weight, -8.6%; biparietal diameter/body weight ratio, +7.5%) in the hatchlings (all P<0.05). At adulthood (181±4 days), chickens from hypoxic incubations remained smaller (body weight, -7.5%) and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to NG-nitro-L-arginine methyl ester, -43%; phenylephrine pressor response during NO blockade, -61%) with significant hypertension (mean arterial blood pressure, +18%), increased cardiac work (ejection fraction, +12%; fractional shortening, +25%; enhanced baroreflex gain, +456%), and left ventricular wall thickening (left ventricular wall volume, +36%; all P<0.05). Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction, and cardiac wall remodeling in adulthood in the absence of any maternal or placental effects.The British Heart Foundation The Wellcome Trus

Similarities and differences of pumping conventional and self-compacting concrete

In Practice, Self-Compacting Concrete (SCC) is Considered as a Simple Extension of Conventional Vibrated Concrete (CVC) When Pumping is Concerned. the Same Equipment, Materials, Pumping Procedures and Guidelines Used for CVC Are Applied When Pumping SCC. on the Other Hand, It Has Been Clearly Shown that the Rheological Properties and the Mix Design of SCC Are Different Than CVC. Can the Same Pumping Principles Employed for CVC Be Applied for SCC? This Paper Compares the Some Published Results of Pumping of CVC with Those for SCC. a First Striking Difference between Pumping of CVC and SCC is the Flow Behaviour in the Pipes. the Flow of CVC is a Plug, Surrounded by a Lubricating Layer, While during the Flow of SCC, Part of the Concrete Volume itself is Sheared Inside the Pipe. as a Result, the Importance of Viscosity Increases in Case of SCC. Due to the Low Yield Stress of SCC, the Behaviour in Bends is Different, But Quite Complex to Study. Due to the Lower Content of Aggregate and Better Stability of SCC, as It is Less Prone to Internal Water Migration, Blocking is Estimated to Occur at Lower Frequency in Case of SCC. © RILEM 2010

Validation of a social cohesion theoretical framework: a multiple group SEM strategy

Social cohesion dates back to the end of the nineteenth century. Back then, society experienced epochal transformations, as are also happening nowadays. Whenever there are epochal changes, a social order (cohesion) matter arises. The paper provides a conceptual scheme of social cohesion identifying its constituent dimensions subdivided by three spheres (macro, meso, micro) and two perspectives (objective and subjective). The overarching aim is to test the validity of the operationalization of the social cohesion model provided. Firstly, we conducted an exploratory factor analysis introducing an approach implemented in Mplus named exploratory structural equation modeling that shows several useful characteristics. Afterward, through a structural equation modeling approach, we performed several confirmatory factor analyses adopting a multiple group SEM strategy in order to cross-validate the social cohesion model

State of the Art on Prediction of Concrete Pumping

Large scale constructions needs to estimate a possibility for pumping concrete. In this paper, the state of the art on prediction of concrete pumping including analytical and experimental works is presented. The existing methods to measure the rheological properties of slip layer (or called lubricating layer) are first introduced. Second, based on the rheological properties of slip layer and parent concrete, models to predict concrete pumping (flow rate, pumping pressure, and pumpable distance) are explained. Third, influencing factors on concrete pumping are discussed with the test results of various concrete mixes. Finally, future need for research on concrete pumping is suggested.ope

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Thoracic myelopathy caused by ossification of ligamentum flavum of which fluorosis as an etiology factor

PURPOSE: To evaluate the clinical feature, operative method and prognosis of thoracic ossification of ligamentum flavum caused by skeletal fluorosis. METHODS: All the patients with thoracic OLF, who underwent surgical management in the authors' hospital from 1993–2003, were retrospectively studied. The diagnosis of skeletal fluorosis was made by the epidemic history, clinical symptoms, radiographic findings, and urinalysis. En bloc laminectomy decompression of the involved thoracic levels was performed in all cases. Cervical open door decompression or lumbar laminectomy decompression was performed if relevant stenosis existed. The neurological statuses were evaluated with the Japanese Orthopaedic Association (JOA) scoring system preoperatively and at the end point of follow up. Also, the recovery rate was calculated. RESULTS: 23 cases have been enrolled in this study. Imaging study findings showed all the cases have ossification of ligamentum flavum together with ossification of many other ligaments and interosseous membranes, i.e. interosseous membranes of the forearm in 18 of 23 (78.3%), of the leg in 14 of 23 (60.1%) and of the ribs in 11 of 23 (47.8%). Urinalysis showed markedly increased urinary fluoride in 14 of 23 patients (60.9%). All the patients were followed up from 12 months to 9 years and 3 months, with an average of 4 years and 5 months. The JOA score increased significantly at the end of follow up (P = 0.0001). The recovery rate was 51.83 ± 32.36%. Multiple regression analysis revealed that the preoperative JOA score was an important predictor of surgical outcome (p = 0.0022, r = 0.60628). ANOVA analysis showed that patients with acute onset or too long duration had worse surgical result (P = 0.0003). CONCLUSION: Fluorosis can cause ossification of thoracic ligamentum flavum, as well as other ligaments. En bloc laminectomy decompression was an effective method. Preoperative JOA score was the most important predictor of surgical outcome. Patients with acute onset or too long duration had worse surgical outcome

Exploring the usability of a connected autonomous vehicle human machine interface designed for older adults

Users of Level 4–5 connected autonomous vehicles (CAVs) should not need to intervene with the dynamic driving task or monitor the driving environment, as the system will handle all driving functions. CAV human-machine interface (HMI) dashboards for such CAVs should therefore offer features to support user situation awareness (SA) and provide additional functionality that would not be practical within non-autonomous vehicles. Though, the exact features and functions, as well as their usability, might differ depending on factors such as user needs and context of use. The current paper presents findings from a simulator trial conducted to test the usability of a prototype CAV HMI designed for older adults and/or individuals with sensory and/or physical impairments: populations that will benefit enormously from the mobility afforded by CAVs. The HMI was developed to suit needs and requirements of this demographic based upon an extensive review of HMI and HCI principles focused on accessibility, usability and functionality [1, 2], as well as studies with target users. Thirty-one 50-88-year-olds (M 67.52, three 50–59) participated in the study. They experienced four seven-minute simulated journeys, involving inner and outer urban settings with mixed speed-limits and were encouraged to explore the HMI during journeys and interact with features, including a real-time map display, vehicle status, emergency stop, and arrival time. Measures were taken pre-, during- and post- journeys. Key was the System Usability Scale [3] and measures of SA, task load, and trust in computers and automation. As predicted, SA decreased with journey experience and although cognitive load did not, there were consistent negative correlations. System usability was also related to trust in technology but not trust in automation or attitudes towards computers. Overall, the findings are important for those designing, developing and testing CAV HMIs for older adults and individuals with sensory and/or physical impairments

Firsthand Experience and The Subsequent Role of Reflected Knowledge in Cultivating Trust in Global Collaboration

While scholars contend that firsthand experience - time spent onsite observing the people, places, and norms of a distant locale - is crucial in globally distributed collaboration, how such experience actually affects interpersonal dynamics is poorly understood. Based on 47 semistructured interviews and 140 survey responses in a global chemical company, this paper explores the effects of firsthand experience on intersite trust. We find firsthand experience leads not just to direct knowledge of the other, but also knowledge of the self as seen through the eyes of the other - what we call “reflected knowledge”. Reflected and direct knowledge, in turn, affect trust through identification, adaptation, and reduced misunderstandings

Assessment and Etiology of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder in Boys and Girls

Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are more common in boys than girls. In this paper, we investigated whether the prevalence differences are attributable to measurement bias. In addition, we examined sex differences in the genetic and environmental influences on variation in these behaviors. Teachers completed the Conners Teacher Rating Scale-Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year-old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were found, implying the absence of measurement bias. The heritabilities for both ADHD and ODD were high and were the same in boys and girls. However, partly different genes are expressed in boys and girls

Mutagenesis Objective Search and Selection Tool (MOSST): an algorithm to predict structure-function related mutations in proteins

<p>Abstract</p> <p>Background</p> <p>Functionally relevant artificial or natural mutations are difficult to assess or predict if no structure-function information is available for a protein. This is especially important to correctly identify functionally significant non-synonymous single nucleotide polymorphisms (nsSNPs) or to design a site-directed mutagenesis strategy for a target protein. A new and powerful methodology is proposed to guide these two decision strategies, based only on conservation rules of physicochemical properties of amino acids extracted from a multiple alignment of a protein family where the target protein belongs, with no need of explicit structure-function relationships.</p> <p>Results</p> <p>A statistical analysis is performed over each amino acid position in the multiple protein alignment, based on different amino acid physical or chemical characteristics, including hydrophobicity, side-chain volume, charge and protein conformational parameters. The variances of each of these properties at each position are combined to obtain a global statistical indicator of the conservation degree of each property. Different types of physicochemical conservation are defined to characterize relevant and irrelevant positions. The differences between statistical variances are taken together as the basis of hypothesis tests at each position to search for functionally significant mutable sites and to identify specific mutagenesis targets. The outcome is used to statistically predict physicochemical consensus sequences based on different properties and to calculate the amino acid propensities at each position in a given protein. Hence, amino acid positions are identified that are putatively responsible for function, specificity, stability or binding interactions in a family of proteins. Once these key functional positions are identified, position-specific statistical distributions are applied to divide the 20 common protein amino acids in each position of the protein's primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids.</p> <p>Conclusions</p> <p>With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins.</p