Rapid determination of single base mismatch mutations in DNA hybrids by direct electric field control

We have demonstrated that controlled electric fields can be used to regulate transport, concentration, hybridization, and denaturation of single- and double-stranded oligonucleotides. Discrimination among oligonucleotide hybrids with widely varying binding strengths may be attained by simple adjustment of the electric field strength. When this approach is used, electric field denaturation control allows single base pair mismatch discrimination to be carried out rapidly (<15 sec) and with high resolution. Electric field denaturation takes place at temperatures well below the melting point of the hybrids, and it may constitute a novel mechanism of DNA denaturation.     

Variation in stated management of acute myocardial infarction in five countries

We examined the variation in stated practice in the management of acute myocardial infarction (AMI) among doctors in Australia, Brazil, Chile, India and Thailand. Hospitals were identified as primary, secondary or tertiary by investigators from around their own region. All doctors within each hospital who would be expected to treat patients with AMI were asked to indicate which investigations and treatments they would offer to a patient with an AMI who develops angina on Day 3 after admission. The numbers of hospitals ranged from 5 to 26 per country, and doctor response rates varied from 70 to 100%. Within-country variation was large, and statistically significant variations were seen between countries in the use of most interventions. The large variation both between and within a range of countries across the economic spectrum suggests a widespread need for agreement about what constitutes appropriate management after AMI.     

The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis

Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range of MNCs suitable for transplantation (10 to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at > 0.7 x 10(6)/graft) determined the yield of human cells produced in recipient animals. Engraftment of hu PBSC preparations resulted in prolonged generation of physiologic levels of human cytokines including interleukin-3 (IL-3), IL-6, and granulocyte- macrophage colony-stimulating factor, which were detectable in the murine blood over a period of at least 4 months. In vivo survival of immature human progenitor cells was preserved even 9 months after transplantation. Because human IL-3 is known to stimulate early hematopoiesis, a rat fibroblast cell line was stably transfected with a retroviral vector carrying the human IL-3 gene and cotransplanted subcutaneously as additional source of growth factor. Cotransplants of this cell line producing sustained in vivo levels of circulating human IL-3 for at least 12 weeks significantly accelerated the process of engraftment of huPBSC and spurred the spread of mature human cells to the murine spleen, liver, thymus, and peripheral blood. Cotransplants of allogeneic human bone marrow stromal cells derived from long-term cultures resulted in a comparable--though less prominent--support of engraftment.     

Childhood abuse history and attention bias in adults

Attention biases toward unpleasant information are evident among children and adults with a history of abuse and have been identified as a potential pathway through which abused children develop psychopathology. Identifying whether a history of childhood abuse affects the time course of attention biases in adults is critical, as this may provide intervention targets. The present study examined the time course of attention bias during an emotion-word Stroop task using event-related potentials (ERPs) in a sample of adults with a range of child abuse histories using a categorical approach (comparing adults with or without a history of moderate-to-severe childhood abuse) and a dimensional approach (analyzing the range from no abuse to severe abuse in a continuous manner). Although behavioral performance did not vary as a function of abuse history, adults with a history of moderate-to-severe childhood abuse showed ERP evidence of early reduced processing of emotional stimuli (smaller N200) and later reduced processing of emotional and nonemotional stimuli (smaller P300), followed by later increased processing of unpleasant stimuli (larger slow wave [SW]). Results suggest that early disengagement from emotional stimuli may help individuals with moderate-to-severe abuse histories to achieve normal behavioral performance on the emotion-word Stroop task. Additionally, regardless of analytic approach, adults with elevated levels of childhood abuse exhibited prolonged engagement (larger SW) specifically with unpleasant stimuli. Present results demonstrate attention bias patterns in adults with a history of childhood abuse and clarify the time course of attention bias. Results are discussed in the context of potential treatment implications.     

Characterization Methods along the Process Chain of Electrical Steel Sheet—From Best Practices to Advanced Characterization

Non-oriented (NO) electrical steel sheets find their application in rotating electrical machines, ranging from generators for wind turbines to motors for the transportation sector and small motors for kitchen appliances. With the current trend of moving away from fossil fuel-based energy conversion towards an electricity-based one, these machines become more and more important and, as a consequence, the leverage effect in saving energy by improving efficiency is huge. It is already well established that different applications of an electrical machine have individual requirements for the properties of the NO electrical steel sheets, which in turn result from the microstructures and textures thereof. However, designing and producing tailor-made NO electrical steel sheet is still challenging, because the complex interdependence between processing steps, the different phenomena taking place and the resulting material properties are still not sufficiently understood. This work shows how established, as well as advanced and newly developed characterization methods, can be used to unfold these intricate connections. In this context, the respective characterization methods are explained and applied to NO electrical steel as well as to the typical processing steps. In addition, several experimental results are reviewed to show the strengths of the different methods, as well as their (dis)advantages, typical applications and obtainable data.     

Free Zinc as a Predictive Marker for COVID-19 Mortality Risk

Free zinc is considered to be the exchangeable and biological active form of zinc in serum, and is discussed to be a suitable biomarker for alterations in body zinc homeostasis and related diseases. Given that coronavirus disease 2019 (COVID-19) is characterized by a marked decrease in total serum zinc, and clinical data indicate that zinc status impacts the susceptibility and severity of the infection, we hypothesized that free zinc in serum might be altered in response to SARS-CoV-2 infection and may reflect disease severity. To test this hypothesis, free zinc concentrations in serum samples of survivors and nonsurvivors of COVID-19 were analyzed by fluorometric microassay. Similar to the reported total serum zinc deficit measured by total reflection X-ray fluorescence, free serum zinc in COVID-19 patients was considerably lower than that in control subjects, and surviving patients displayed significantly higher levels of free zinc than those of nonsurvivors (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0004). In contrast to recovering total zinc concentrations (r = 0.706, p < 0.001) or the declining copper–zinc ratio (r = −0.646; p < 0.001), free zinc concentrations remained unaltered with time in COVID-19 nonsurvivors. Free serum zinc concentrations were particularly low in male as compared to female patients (mean ± SD; 0.4 ± 0.2 nM vs. 0.2 ± 0.1 nM; p = 0.0003). This is of particular interest, as the male sex is described as a risk factor for severe COVID-19. Overall, results indicate that depressed free serum zinc levels are associated with increased risk of death in COVID-19, suggesting that free zinc may serve as a novel prognostic marker for the severity and course of COVID-19.