Application of thermoluminescence for detection of cascade shower 1: Hardware and software of reader system

A reader system for the detection of cascade showers via luminescence induced by heating sensitive material (BaSO4:Eu) is developed. The reader system is composed of following six instruments: (1) heater, (2) light guide, (3) image intensifier, (4) CCD camera, (5) image processor, (6) microcomputer. The efficiency of these apparatuses and software application for image analysis is reported

Application of thermoluminescence for detection of cascade shower 2: Detection of cosmic ray cascade shower at Mount Fuji

The results of a thermoluminescence (TL) chamber exposed at Mt. Fuji during Aug. '83 - Aug. '84 are reported. The TL signal induced by cosmic ray shower is detected and compared with the spot darkness of X-ray film exposed at the same time

CREB is a critical regulator of normal hematopoiesis and leukemogenesis

The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

Universality of weak selection

Weak selection, which means a phenotype is slightly advantageous over another, is an important limiting case in evolutionary biology. Recently it has been introduced into evolutionary game theory. In evolutionary game dynamics, the probability to be imitated or to reproduce depends on the performance in a game. The influence of the game on the stochastic dynamics in finite populations is governed by the intensity of selection. In many models of both unstructured and structured populations, a key assumption allowing analytical calculations is weak selection, which means that all individuals perform approximately equally well. In the weak selection limit many different microscopic evolutionary models have the same or similar properties. How universal is weak selection for those microscopic evolutionary processes? We answer this question by investigating the fixation probability and the average fixation time not only up to linear, but also up to higher orders in selection intensity. We find universal higher order expansions, which allow a rescaling of the selection intensity. With this, we can identify specific models which violate (linear) weak selection results, such as the one--third rule of coordination games in finite but large populations.Comment: 12 pages, 3 figures, accepted for publication in Physical Review

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Amplified biochemical oscillations in cellular systems

We describe a mechanism for pronounced biochemical oscillations, relevant to microscopic systems, such as the intracellular environment. This mechanism operates for reaction schemes which, when modeled using deterministic rate equations, fail to exhibit oscillations for any values of rate constants. The mechanism relies on amplification of the underlying stochasticity of reaction kinetics within a narrow window of frequencies. This amplification allows fluctuations to beat the central limit theorem, having a dominant effect even though the number of molecules in the system is relatively large. The mechanism is quantitatively studied within simple models of self-regulatory gene expression, and glycolytic oscillations.Comment: 35 pages, 6 figure

Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

Time resolved spectroscopy of BD+46 442: gas streams and jet creation in a newly discovered evolved binary with a disk

Previous studies have shown that many post-AGB stars with dusty disks are associated with single-lined binary stars. To verify the binarity hypothesis on a larger sample, we started a high-resolution spectral monitoring of about 40 field giants, whose binarity was suspected based on either a light curve, an infrared excess, or a peculiar chemical composition. Here we report on the discovery of the periodic RV variations in BD+46 442, a high-latitude F giant with a disk. We interpret the variations due to the motion around a faint companion, and deduce the following orbital parameters: Porb = 140.77 d, e = 0.083, asini=0.31 AU. We find it to be a moderately metal-poor star ([M/H]=-0.7) without a strong depletion pattern in the photospheric abundances. Interestingly, many lines show periodic changes with the orbital phase: Halpha switches between a double-peak emission and a PCyg-like profiles, while strong metal lines appear split during the maximum redshift. Similar effects are likely visible in the spectra of other post-AGB binaries, but their regularity is not always realized due to sporadic observations. We propose that these features result from an ongoing mass transfer from the evolved giant to the companion. In particular, the blue-shifted absorption in Halpha, which occurs only at superior conjunction, may result from a jet originating in the accretion disk around the companion and seen in absorption towards the luminous primary.Comment: 16 pages, accepted in A&

The Majorana Project

Building a \BBz experiment with the ability to probe neutrino mass in the inverted hierarchy region requires the combination of a large detector mass sensitive to \BBz, on the order of 1-tonne, and unprecedented background levels, on the order of or less than 1 count per year in the \BBz signal region. The MAJORANA Collaboration proposes a design based on using high-purity enriched Ge-76 crystals deployed in ultra-low background electroformed Cu cryostats and using modern analysis techniques that should be capable of reaching the required sensitivity while also being scalable to a 1-tonne size. To demonstrate feasibility, the collaboration plans to construct a prototype system, the MAJORANA DEMONSTRATOR, consisting of 30 kg of 86% enriched \Ge-76 detectors and 30 kg of natural or isotope-76-depleted Ge detectors. We plan to deploy and evaluate two different Ge detector technologies, one based on a p-type configuration and the other on n-type.Comment: paper submitted for the 2008 Carolina International Symposium on Neutrino Physic

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution