Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Visualization methods for statistical analysis of microarray clusters

BACKGROUND: The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gold-standard. Appropriate data visualization tools can aid this analysis process, but existing visualization methods do not specifically address this issue. RESULTS: We present several visualization techniques that incorporate meaningful statistics that are noise-robust for the purpose of analyzing the results of clustering algorithms on microarray data. This includes a rank-based visualization method that is more robust to noise, a difference display method to aid assessments of cluster quality and detection of outliers, and a projection of high dimensional data into a three dimensional space in order to examine relationships between clusters. Our methods are interactive and are dynamically linked together for comprehensive analysis. Further, our approach applies to both protein and gene expression microarrays, and our architecture is scalable for use on both desktop/laptop screens and large-scale display devices. This methodology is implemented in GeneVAnD (Genomic Visual ANalysis of Datasets) and is available at . CONCLUSION: Incorporating relevant statistical information into data visualizations is key for analysis of large biological datasets, particularly because of high levels of noise and the lack of a gold-standard for comparisons. We developed several new visualization techniques and demonstrated their effectiveness for evaluating cluster quality and relationships between clusters

Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy

Rapid evolution is central to the current antibiotic crisis. Sustainable treatments must thus take account of the bacteria’s potential for adaptation. We identified cellular hysteresis as a principle to constrain bacterial evolution. Cellular hysteresis is a persistent change in bacterial physiology, reminiscent of cellular memory, which is induced by one antibiotic and enhances susceptibility toward another antibiotic. Cellular hysteresis increases bacterial extinction in fast sequential treatments and reduces selection of resistance by favoring responses specific to the induced physiological effects. Fast changes between antibiotics are key, because they create the continuously high selection conditions that are difficult to counter by bacteria. Our study highlights how an understanding of evolutionary processes can help to outsmart human pathogens.Antibiotic resistance has become one of the most dramatic threats to global health. While novel treatment options are urgently required, most attempts focus on finding new antibiotic substances. However, their development is costly, and their efficacy is often compromised within short time periods due to the enormous potential of microorganisms for rapid adaptation. Here, we developed a strategy that uses the currently available antibiotics. Our strategy exploits cellular hysteresis, which is the long-lasting, transgenerational change in cellular physiology that is induced by one antibiotic and sensitizes bacteria to another subsequently administered antibiotic. Using evolution experiments, mathematical modeling, genomics, and functional genetic analysis, we demonstrate that sequential treatment protocols with high levels of cellular hysteresis constrain the evolving bacteria by (i) increasing extinction frequencies, (ii) reducing adaptation rates, and (iii) limiting emergence of multidrug resistance. Cellular hysteresis is most effective in fast sequential protocols, in which antibiotics are changed within 12 h or 24 h, in contrast to the less frequent changes in cycling protocols commonly implemented in hospitals. We found that cellular hysteresis imposes specific selective pressure on the bacteria that disfavors resistance mutations. Instead, if bacterial populations survive, hysteresis is countered in two distinct ways, either through a process related to antibiotic tolerance or a mechanism controlled by the previously uncharacterized two-component regulator CpxS. We conclude that cellular hysteresis can be harnessed to optimize antibiotic therapy, to achieve both enhanced bacterial elimination and reduced resistance evolution

Spontaneous Coronary Artery Dissection as Presenting Feature of Vascular Ehlers-Danlos Syndrome

A spontaneous coronary artery dissection as the sole presenting feature of vascular Ehlers-Danlos syndrome is an uncommon finding. We present a 33-year-old woman with sudden onset chest pain caused by a spontaneous coronary artery dissection. Genetic testing revealed vascular Ehlers-Danlos syndrome as the underlying cause. Specifically, we show the value of genetic testing, which in some patients may be the only way of establishing a diagnosis

Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs

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High-dose chemotherapy followed by autologous haematopoietic cell transplantation for children, adolescents, and young adults with first recurrence of Ewing sarcoma

BACKGROUND Ewing sarcoma is a solid tumour, which is the second most common primary bone malignancy in children, often occurring in the long bones and pelvis. An incidence rate of 4.5 per million a year is reported, with a peak incidence of 11 per million at the age of 12 years. Despite more intensive chemotherapy, 30% to 40% of young people with Ewing sarcoma will have recurrence of the disease. Less than 30% of young people with a recurrence of Ewing sarcoma are alive at 24 months, and less than 10% are alive at 48 months. High-dose chemotherapy (HDC), followed by autologous haematopoietic cell transplantation (AHCT), is used in a variety of paediatric groups with diverse solid tumours. The hypothesis is that HDC regimens may overcome resistance to standard polychemotherapy, and this way may eradicate minimal residual disease, leading to improved survival after a first recurrence of disease. OBJECTIVES To assess the efficacy of HDC with AHCT versus conventional chemotherapy in improving event-free survival, overall survival, quality-adjusted survival, and progression-free survival in children, adolescents, and young adults with first recurrence of Ewing sarcoma, and to determine the toxicity of the treatment. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, conference proceedings from the SIOP, ASPHO, CTOS, ASBMT, EBMT, and EMSOS, and two trial registries in January 2020. We also searched reference lists of relevant articles and review articles. SELECTION CRITERIA We planned to include randomised controlled trials (RCTs) or (historical) controlled clinical trials (CCTs) comparing the effectiveness of HDC plus AHCT with conventional chemotherapy for children, adolescents, and young adults (up to 30 years old at the date of diagnostic biopsy) with a first recurrence of Ewing sarcoma. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We did not identify any eligible studies. AUTHORS' CONCLUSIONS Since we did not identify any eligible studies, we are unable to draw any conclusions about the efficacy and toxicity of HDC with AHCT versus conventional chemotherapy in children, adolescents, and young adults with a first recurrence of Ewing sarcoma. Further high-quality research is urgently needed

Simplified Multistep Outflow Method to Estimate Unsaturated Hydraulic Functions for Coarse-Textured Soils

Although the multistep outfl ow (MSO) method is well suited for the estimation of soil hydraulic properties by inverse solution techniques, this method has not been widely adopted because it requires advanced instrumentation and is time consuming. Th e objective of this study was to develop a modifi ed version of the multistep outfl ow technique that largely simplifi es laboratory procedures and reduces costs and time. Th e numerical inversion procedures require applying user-friendly HYDRUS soft ware to estimate fi tting parameters for soil water retention and unsaturated hydraulic conductivity curves. Whereas values of saturated water content and saturated hydraulic conductivity must be measured independently, the remaining functional parameters are estimated using an inverse solution of a transient drainage experiment using multiple suction steps and a hanging water column, with drainage outfl ows measured during drainage. A comparison test showed that the simplifi ed experiment without tensiometric measurements provided suffi cient information in the parameter identifi cation compared with a traditional pressure outfl ow experiment with tensiometric measurements for an Oso Flaco sand and a loamy sand fi eld soil in the suction range of 0 to 17 kPa

A multi-parent recombinant inbred line population of C. elegans allows identification of novel QTLs for complex life history traits

Background The nematode Caenorhabditis elegans has been extensively used to explore the relationships between complex traits, genotypes, and environments. Complex traits can vary across different genotypes of a species, and the genetic regulators of trait variation can be mapped on the genome using quantitative trait locus (QTL) analysis of recombinant inbred lines (RILs) derived from genetically and phenotypically divergent parents. Most RILs have been derived from crossing two parents from globally distant locations. However, the genetic diversity between local C. elegans populations can be as diverse as between global populations and could thus provide means of identifying genetic variation associated with complex traits relevant on a broader scale. Results To investigate the effect of local genetic variation on heritable traits, we developed a new RIL population derived from 4 parental wild isolates collected from 2 closely located sites in France: Orsay and Santeuil. We crossed these 4 genetically diverse parental isolates to generate a population of 200 multi-parental RILs and used RNA-seq to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the 4 genotypes with an average spacing of 11 kb, doubling the mapping resolution relative to currently available RIL panels for many loci. The SNPs were used to construct a genetic map to facilitate QTL analysis. We measured life history traits such as lifespan, stress resistance, developmental speed, and population growth in different environments, and found substantial variation for most traits. We detected multiple QTLs for most traits, including novel QTLs not found in previous QTL analysis, including those for lifespan and pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Conclusion Taken together, we show that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates facilitates the detection of QTLs. The use of multi-parent RIL populations can further enhance our understanding of local adaptation and life history trade-offs