Validation of DNA probes for molecular cytogenetics by mapping onto immobilized circular DNA

<p>Abstract</p> <p>Background</p> <p>Fluorescence <it>in situ </it>hybridization (FISH) is a sensitive and rapid procedure to detect gene rearrangements in tumor cells using non-isotopically labeled DNA probes. Large insert recombinant DNA clones such as bacterial artificial chromosome (BAC) or P1/PAC clones have established themselves in recent years as preferred starting material for probe preparations due to their low rates of chimerism and ease of use. However, when developing probes for the quantitative analysis of rearrangements involving genomic intervals of less than 100 kb, careful probe selection and characterization are of paramount importance.</p> <p>Results</p> <p>We describe a sensitive approach to quality control probe clones suspected of carrying deletions or for measuring clone overlap with near kilobase resolution. The method takes advantage of the fact that P1/PAC/BAC's can be isolated as circular DNA molecules, stretched out on glass slides and fine-mapped by multicolor hybridization with smaller probe molecules. Two examples demonstrate the application of this technique: mapping of a gene-specific ~6 kb plasmid onto an unusually small, ~55 kb circular P1 molecule and the determination of the extent of overlap between P1 molecules homologous to the human NF-κB2 locus.</p> <p>Conclusion</p> <p>The relatively simple method presented here does not require specialized equipment and may thus find widespread applications in DNA probe preparation and characterization, the assembly of physical maps for model organisms or in studies on gene rearrangements.</p

Rieger, Schwabe, Suess-de Vries: The Sunny Beats of Resonance

We propose a self-consistent explanation of Rieger-type periodicities, the Schwabe cycle, and the Suess-de Vries cycle in terms of resonances of various wave phenomena with gravitational forces exerted by the orbiting planets. Starting on the high-frequency side, we show that the two-planet spring tides of Venus, Earth and Jupiter are able to excite magneto-Rossby waves which can be linked with typical Rieger-type periods. We argue then that the 11.07-year beat period of those magneto-Rossby waves synchronizes an underlying conventional $\alpha-\Omega$-dynamo, by periodically changing either the field storage capacity in the tachocline or some portion of the $\alpha$-effect therein. We also strengthen the argument that the Suess-de Vries cycle appears as an 193-year beat period between the 22.14-year Hale cycle and a spin-orbit coupling effect related with the 19.86-year rosette-like motion of the Sun around the barycenter.Comment: 31 pages, 12 figure

An analysis of eye-tracking data in foveated ray tracing

We present an analysis of eye tracking data produced during a quality-focused user study of our own foveated ray tracing method. Generally, foveated rendering serves the purpose of adapting actual rendering methods to a user’s gaze. This leads to performance improvements which also allow for the use of methods like ray tracing, which would be computationally too expensive otherwise, in fields like virtual reality (VR), where high rendering performance is important to achieve immersion, or fields like scientific and information visualization, where large amounts of data may hinder real-time rendering capabilities. We provide an overview of our rendering system itself as well as information about the data we collected during the user study, based on fixation tasks to be fulfilled during flights through virtual scenes displayed on a head-mounted display (HMD). We analyze the tracking data regarding its precision and take a closer look at the accuracy achieved by participants when focusing the fixation targets. This information is then put into context with the quality ratings given by the users, leading to a surprising relation between fixation accuracy and quality ratings.We would like to thank NVIDIA for providing us with two Quadro K6000 graphics cards for the user study, the Intel Visual Computing Institute, the European Union (EU) for the co-funding as part of the Dreamspace project, the German Federal Ministry for Economic Affairs and Energy (BMWi) for funding the MATEDIS ZIM project (grant no KF2644109) and the Federal Ministry of Education and Research (BMBF) for funding the project OLIVE

Assessing the public health impacts of legalizing recreational cannabis use in the USA

A major challenge in assessing the public health impact of legalizing cannabis use in Colorado and Washington State is the absence of any experience with legal cannabis markets. The Netherlands created a de facto legalized cannabis market for recreational use, but policy analysts disagree about how it has affected rates of cannabis use. Some US states have created de facto legal supply of cannabis for medical use. So far this policy does not appear to have increased cannabis use or cannabis-related harm. Given experience with more liberal alcohol policies, the legalization of recreational cannabis use is likely to increase use among current users. It is also likely that legalization will increase the number of new users among young adults but it remains uncertain how many may be recruited, within what time frame, among which groups within the population, and how many of these new users will become regular users

IRF5 Is a Key Regulator of Macrophage Response to Lipopolysaccharide in Newborns.

Infections are a leading cause of mortality and morbidity in newborns. The high susceptibility of newborns to infection has been associated with a limited capacity to mount protective immune responses. Monocytes and macrophages are involved in the initiation, amplification, and termination of immune responses. Depending on cues received from their environment, monocytes differentiate into M1 or M2 macrophages with proinflammatory or anti-inflammatory and tissue repair properties, respectively. The purpose of this study was to characterize differences in monocyte to macrophage differentiation and polarization between newborns and adults. Monocytes from umbilical cord blood of healthy term newborns and from peripheral blood of adult healthy subjects were exposed to GM-CSF or M-CSF to induce M1 or M2 macrophages. Newborn monocytes differentiated into M1 and M2 macrophages with similar morphology and expression of differentiation/polarization markers as adult monocytes, with the exception of CD163 that was expressed at sevenfold higher levels in newborn compared to adult M1 macrophages. Upon TLR4 stimulation, newborn M1 macrophages produced threefold to sixfold lower levels of TNF than adult macrophages, while production of IL-1-β, IL-6, IL-8, IL-10, and IL-23 was at similar levels as in adults. Nuclear levels of IRF5, a transcription factor involved in M1 polarization, were markedly reduced in newborns, whereas the NF-κB and MAP kinase pathways were not altered. In line with a functional role for IRF5, adenoviral-mediated IRF5 overexpression in newborn M1 macrophages restored lipopolysaccharide-induced TNF production. Altogether, these data highlight a distinct immune response of newborn macrophages and identify IRF5 as a key regulator of macrophage TNF response in newborns

Estimating the number of regular and dependent methamphetamine users in Australia, 2002-2014.

Objective: To estimate the number of regular and dependent methamphetamine users in Australia. Design: Indirect prevalence estimates were made for each year from 2002–03 to 2013–14. We applied multiplier methods to data on treatment episodes for amphetamines (eg, counselling, rehabilitation, detoxification) and amphetamine-related hospitalisations to estimate the numbers of regular (at least monthly) and dependent methamphetamine users for each year. Dependent users comprised a subgroup of those who used the drug regularly, so that estimates of the sizes of these two populations were not additive. Results: We estimated that during 2013–14 there were 268 000 regular methamphetamine users (95% CI, 187 000–385 000) and 160 000 dependent users (95% CI, 110 000–232 000) aged 15–54 years in Australia. This equated to population rates of 2.09% (95% CI, 1.45–3.00%) for regular and 1.24% (95% CI, 0.85–1.81%) for dependent use. The rate of dependent use had increased since 2009–10 (when the rate was estimated to be 0.74%), and was higher than the previous peak (1.22% in 2006–07). The highest rates were consistently among those aged 25–34 years, in whom the rate of dependent use during 2012–2013 was estimated to be 1.50% (95% CI, 1.05–2.22%). There had also been an increase in the rate of dependent use among those aged 15–24 years (in 2012–13 reaching 1.14%; 95% CI, 0.80–1.69%). Conclusions: There have been increases over the past 12 years in the numbers of regular and dependent methamphetamine users in Australia. Our estimates suggest that the most recent numbers are the highest for this period, and that the increase has been most marked among young adults (those aged 15–34 years)