Synthesis of new spin labels for Cu-free click conjugation

New pyrroline nitroxides attached to a terminal acetylenic sulfone, a dibenzocyclooctyne or a cyclooctyne carboxylic acid were synthesized and tested in Cu-free click reactions to conjugate these new spin labels with 4-azido-TEMPO, azidophenylalanine and an azidophenylalanine-containing protein

Coincidence between transcriptome analyses on different microarray platforms using a parametric framework

A parametric framework for the analysis of transcriptome data is demonstrated to yield coincident results when applied to data acquired using two different microarray platforms. Discrepancies among transcriptome studies are frequently reported, casting doubt on the reliability of collected data. The inconsistency among observations can be largely attributed to differences among the analytical frameworks employed for data analysis. The existing frameworks normalizes data against a standard determined from the data to be analyzed. In the present study, a parametric framework based on a strict model for normalization is applied to data acquired using an in-house printed chip and GeneChip. The framework is based on a common statistical characteristic of microarray data, and each data is normalized on the basis of a linear relationship with this model. In the proposed framework, the expressional changes observed and genes selected are coincident between platforms, achieving superior universality of data compared to other methods

Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has been implicated with these processes. Herein, we report a specific pH-dependent dimerization of murine VDAC1 (mVDAC1) identified by double electron-electron resonance and native mass spectrometry. Intermolecular distances on four singly spin-labeled mVDAC1 mutants were used to generate a model of the low-pH dimer, establishing the presence of residue E73 at the interface. This dimer arrangement is different from any oligomeric state previously described, and it forms as a steep function of pH with an apparent pKa of 7.4. Moreover, the monomer-dimer equilibrium affinity constant was determined using native MS, revealing a nearly eightfold enhancement in dimerization affinity at low pH. Mutation of E73 to either alanine or glutamine severely reduces oligomerization, demonstrating the role of protonated E73 in enhancing dimer formation. Based on these results, and the known importance of E73 in VDAC physiology, VDAC dimerization likely plays a significant role in mitochondrial metabolic regulation and apoptosis in response to cytosolic acidification during cellular stress

Large Fluctuations and Fixation in Evolutionary Games

We study large fluctuations in evolutionary games belonging to the coordination and anti-coordination classes. The dynamics of these games, modeling cooperation dilemmas, is characterized by a coexistence fixed point separating two absorbing states. We are particularly interested in the problem of fixation that refers to the possibility that a few mutants take over the entire population. Here, the fixation phenomenon is induced by large fluctuations and is investigated by a semi-classical WKB (Wentzel-Kramers-Brillouin) theory generalized to treat stochastic systems possessing multiple absorbing states. Importantly, this method allows us to analyze the combined influence of selection and random fluctuations on the evolutionary dynamics \textit{beyond} the weak selection limit often considered in previous works. We accurately compute, including pre-exponential factors, the probability distribution function in the long-lived coexistence state and the mean fixation time necessary for a few mutants to take over the entire population in anti-coordination games, and also the fixation probability in the coordination class. Our analytical results compare excellently with extensive numerical simulations. Furthermore, we demonstrate that our treatment is superior to the Fokker-Planck approximation when the selection intensity is finite.Comment: 17 pages, 10 figures, to appear in JSTA

On the Absorption of X-rays in the Interstellar Medium

We present an improved model for the absorption of X-rays in the ISM intended for use with data from future X-ray missions with larger effective areas and increased energy resolution such as Chandra and XMM, in the energy range above 100eV. Compared to previous work, our formalism includes recent updates to the photoionization cross section and revised abundances of the interstellar medium, as well as a treatment of interstellar grains and the H2molecule. We review the theoretical and observational motivations behind these updates and provide a subroutine for the X-ray spectral analysis program XSPEC that incorporates our model.Comment: ApJ, in press, for associated software see http://astro.uni-tuebingen.de/nh

Measurement of the Electric and Magnetic Polarizabilities of the Proton

The Compton scattering cross section on the proton has been measured at laboratory angles of 90$^\circ$ and 135$^\circ$ using tagged photons in the energy range 70--100 MeV and simultaneously using untagged photons in the range 100--148~MeV. With the aid of dispersion relations, these cross sections were used to extract the electric and magnetic polarizabilities, $\bar{\alpha}$ and $\bar{\beta}$ respectively, of the proton. We find $$\bar{\alpha}+\bar{\beta} = ( 15.0 \pm 2.9 \pm 1.1 \pm 0.4 ) \times 10^{-4} \: {\rm fm}^3,$$ in agreement with a model-independent dispersion sum rule, and $$\bar{\alpha}-\bar{\beta} = ( 10.8 \pm 1.1 \pm 1.4 \pm 1.0 ) \times 10^{-4} \: {\rm fm}^3,$$ where the errors shown are statistical, systematic, and model-dependent, respectively. A comparison with previous experiments is given and global values for the polarizabilities are extracted.Comment: 35 pages, 11 PostScript figures, uses RevTex 3.

Robustness Against Extinction by Stochastic Sex Determination in Small Populations

Sexually reproducing populations with small number of individuals may go extinct by stochastic fluctuations in sex determination, causing all their members to become male or female in a generation. In this work we calculate the time to extinction of isolated populations with fixed number $N$ of individuals that are updated according to the Moran birth and death process. At each time step, one individual is randomly selected and replaced by its offspring resulting from mating with another individual of opposite sex; the offspring can be male or female with equal probability. A set of $N$ time steps is called a generation, the average time it takes for the entire population to be replaced. The number k of females fluctuates in time, similarly to a random walk, and extinction, which is the only asymptotic possibility, occurs when k=0 or k=N. We show that it takes only one generation for an arbitrary initial distribution of males and females to approach the binomial distribution. This distribution, however, is unstable and the population eventually goes extinct in 2^N/N generations. We also discuss the robustness of these results against bias in the determination of the sex of the offspring, a characteristic promoted by infection by the bacteria Wolbachia in some arthropod species or by temperature in reptiles.Comment: 17 pages, 2 figure

The Moran model as a dynamical process on networks and its implications for neutral speciation

In genetics the Moran model describes the neutral evolution of a bi-allelic gene in a population of haploid individuals subjected to mutations. We show in this paper that this model can be mapped into an influence dynamical process on networks subjected to external influences. The panmictic case considered by Moran corresponds to fully connected networks and can be completely solved in terms of hypergeometric functions. Other types of networks correspond to structured populations, for which approximate solutions are also available. This new approach to the classic Moran model leads to a relation between regular networks based on spatial grids and the mechanism of isolation by distance. We discuss the consequences of this connection for topopatric speciation and the theory of neutral speciation and biodiversity. We show that the effect of mutations in structured populations, where individuals can mate only with neighbors, is greatly enhanced with respect to the panmictic case. If mating is further constrained by genetic proximity between individuals, a balance of opposing tendencies take place: increasing diversity promoted by enhanced effective mutations versus decreasing diversity promoted by similarity between mates. Stabilization occurs with speciation via pattern formation. We derive an explicit relation involving the parameters characterizing the population that indicates when speciation is possible.Comment: Improved analytical treatment of speciatio

A multi-detector array for high energy nuclear e+e- pair spectrosocopy

A multi-detector array has been constructed for the simultaneous measurement of energy- and angular correlation of electron-positron pairs produced in internal pair conversion (IPC) of nuclear transitions up to 18 MeV. The response functions of the individual detectors have been measured with mono-energetic beams of electrons. Experimental results obtained with 1.6 MeV protons on targets containing $^{11}$B and $^{19}$F show clear IPC over a wide angular range. A comparison with GEANT simulations demonstrates that angular correlations of $e^+e^-$ pairs of transitions in the energy range between 6 and 18 MeV can be determined with sufficient resolution and efficiency to search for deviations from IPC due to the creation and subsequent decay into $e^+e^-$ of a hypothetical short-lived neutral boson.Comment: 20 pages, 8 figure