Method and apparatus for evaluating multilayer objects for imperfections

A multilayer object having multiple layers arranged in a stacking direction is evaluated for imperfections such as voids, delaminations and microcracks. First, an acoustic wave is transmitted into the object in the stacking direction via an appropriate transducer/waveguide combination. The wave propagates through the multilayer object and is received by another transducer/waveguide combination preferably located on the same surface as the transmitting combination. The received acoustic wave is correlated with the presence or absence of imperfections by, e.g., generating pulse echo signals indicative of the received acoustic wave, wherein the successive signals form distinct groups over time. The respective peak amplitudes of each group are sampled and curve fit to an exponential curve, wherein a substantial fit of approximately 80-90% indicates an absence of imperfections and a significant deviation indicates the presence of imperfections. Alternatively, the time interval between distinct groups can be measured, wherein equal intervals indicate the absence of imperfections and unequal intervals indicate the presence of imperfections

Information Technologies and Education for the Poor in Africa: Recommendations for a Pro-Poor ICT4D Non-Formal Education Policy

More than half of Africa\u27s youth and adults do not have basic literacy skills and/or have not completed primary or secondary school. It is deeply concerning how little serious attention has been paid to the potential ways in which ICT can enhance such skills, as part of a pro-poor model of ICT for Development (ICT4D). Such work is crucial if the goals of Education for All (EFA) and the Millennium Development Goals (MDG) are to be achieved. The present effort, Information Technologies and Education for the Poor in Africa (ITEPA), is designed to focus attention on what is being and has been attempted in this domain in some of the poorest communities in Africa

Comparison of Vlasov-Uehling-Uhlenbeck model with 4 π Heavy Ion Data

Streamer chamber data for collisions of Ar + KCl and Ar + BaI2 at 1.2 GeV/nucleon are compared with microscopic model predictions based on the Vlasov-Uehling-Uhlenbeck equation, for various density-dependent nuclear equations of state. Multiplicity distributions and inclusive rapidity and transverse momentum spectra are in good agreement. Rapidity spectra show evidence of being useful in determining whether the model uses the correct cross sections for binary collisions in the nuclear medium, and whether momentum-dependent interactions are correctly incorporated. Sideward flow results do not favor the same nuclear stiffness parameter at all multiplicities

Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate.

Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 mutation are among the most frequently observed alterations in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there are no biologically relevant models that can be used to assess the molecular mechanisms for these genetic abnormalities. Here, we report a novel mouse model, in which elevated transgenic AR expression and Trp53 deletion occur simultaneously in mouse prostatic epithelium to mimic human prostate cancer cells. These compound mice developed an earlier onset of high-grade prostatic intraepithelial neoplasia and accelerated prostate tumors in comparison with mice harboring only the AR transgene. Histological analysis showed prostatic sarcomatoid and basaloid carcinomas with massive squamous differentiation in the above compound mice. RNA-sequencing analyses identified a robust enrichment of the signature genes for human prostatic basal cell carcinomas in the above prostate tumors. Master regulator analysis revealed SOX2 as a transcriptional regulator in prostatic basal cell tumors. Elevated expression of SOX2 and its downstream target genes were detected in prostatic tumors of the compound mice. Chromatin immunoprecipitation analyses implicate a coregulatory role of AR and SOX2 in the expression of prostatic basal cell signature genes. Our data demonstrate a critical role of SOX2 in prostate tumorigenesis and provide mechanistic insight into prostate tumor aggressiveness and progression mediated by aberrant AR and p53 signaling pathways

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

Chronic CSE Treatment Induces the Growth of Normal Oral Keratinocytes via PDK2 Upregulation, Increased Glycolysis and HIF1α Stabilization

Exposure to cigarette smoke is a major risk factor for head and neck squamous cell carcinoma (HNSCC). We have previously established a chronic cigarette smoke extract (CSE)-treated human oral normal keratinocyte model, demonstrating an elevated frequency of mitochondrial mutations in CSE treated cells. Using this model we further characterized the mechanism by which chronic CSE treatment induces increased cellular proliferation.We demonstrate that chronic CSE treatment upregulates PDK2 expression, decreases PDH activity and thereby increases the glycolytic metabolites pyruvate and lactate. We also found that the chronic CSE treatment enhanced HIF1α accumulation through increased pyruvate and lactate production in a manner selectively reversible by ascorbate. Use of a HIF1α small molecule inhibitor blocked the growth induced by chronic CSE treatment in OKF6 cells. Furthermore, chronic CSE treatment was found to increase ROS (reactive oxygen species) production, and application of the ROS scavengers N-acetylcysteine abrogated the expression of PDK2 and HIF1α. Notably, treatment with dichloroacetate, a PDK2 inhibitor, also decreased the HIF1α expression as well as cell proliferation in chronic CSE treated OKF6 cells.Our findings suggest that chronic CSE treatment contribute to cell growth via increased ROS production through mitochondrial mutations, upregulation of PDK2, attenuating PDH activity thereby increasing glycolytic metabolites, resulting in HIF1α stabilization. This study suggests a role for chronic tobacco exposure in the development of aerobic glycolysis and normoxic HIFα activation as a part of HNSCC initiation. These data may provide insights into development of chemopreventive strategies for smoking related cancers

The speciation and genotyping of Cronobacter isolates from hospitalised patients

The World Health Organization (WHO) has recognised all Cronobacter species as human pathogens. Among premature neonates and immunocompromised infants, these infections can be life-threatening, with clinical presentations of septicaemia, meningitis and necrotising enterocolitis. The neurological sequelae can be permanent and the mortality rate as high as 40 – 80 %. Despite the highlighted issues of neonatal infections, the majority of Cronobacter infections are in the elderly population suffering from serious underlying disease or malignancy and include wound and urinary tract infections, osteomyelitis, bacteraemia and septicaemia. However, no age profiling studies have speciated or genotyped the Cronobacter isolates. A clinical collection of 51 Cronobacter strains from two hospitals were speciated and genotyped using 7-loci multilocus sequence typing (MLST), rpoB gene sequence analysis, O-antigen typing and pulsed- field gel electrophoresis (PFGE). The isolates were predominated by C. sakazakii sequence type 4 (63 %, 32/51) and C. malonaticus sequence type 7 (33 %, 17/51). These had been isolated from throat and sputum samples of all age groups, as well as recal and faecal swabs. There was no apparent relatedness between the age of the patient and the Cronobacter species isolated. Despite the high clonality of Cronobacter , PFGE profiles differentiated strains across the sequence types into 15 pulsotypes. There was almost complete agreement between O-antigen typing and rpoB gene sequence analysis and MLST profiling. This study shows the value of applying MLST to bacterial population studies with strains from two patient cohorts, combined with PFGE for further discrimination of strains

Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12.

Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-resident type 1 ILCs (ILC1s) expanded locally and persisted after the resolution of infection with mouse cytomegalovirus (MCMV). ILC1s acquired stable transcriptional, epigenetic and phenotypic changes a month after the resolution of MCMV infection, and showed an enhanced protective effector response to secondary challenge with MCMV consistent with a memory lymphocyte response. Memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, and were independent of bystander activation by proinflammatory cytokines after heterologous infection. Thus, liver ILC1s acquire adaptive features in an MCMV-specific manner

Brain Age from the Electroencephalogram of Sleep

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as "brain age", which can be compared to an age norm to reflect the deviation from normal aging process. Here, we develop an interpretable machine learning model to predict brain age based on two large sleep EEG datasets: the Massachusetts General Hospital sleep lab dataset (MGH, N = 2,621) covering age 18 to 80; and the Sleep Hearth Health Study (SHHS, N = 3,520) covering age 40 to 80. The model obtains a mean absolute deviation of 8.1 years between brain age and chronological age in the healthy participants in the MGH dataset. As validation, we analyze a subset of SHHS containing longitudinal EEGs 5 years apart, which shows a 5.5 years difference in brain age. Participants with neurological and psychiatric diseases, as well as diabetes and hypertension medications show an older brain age compared to chronological age. The findings raise the prospect of using sleep EEG as a biomarker for healthy brain aging