Bioinformatics

Motivation: Chromatin immunoprecipitation (ChIP) is a powerful experimental approach to identify in vivo binding sites of sequence-specific transcription factors (TFs). These experiments are designed to specifically enrich DNA fragments that are bound to the TF. Tiling arrays have become more and more popular for the identification of these DNA fragments. However, many studies showed that only a fraction of the identified DNA fragments contains bona fide binding sites for the TF, suggesting that indirect binding mechanisms play a very important role. We explored the possibility that the lack of binding sites can also be explained by problems in identifying ChIP-enriched DNA fragments from the measured intensities. Results: We derived a physical model that explains some (but not all) variation of the measured probe intensities of Affymetrix tilling arrays. We used the physical model to estimate the probe-specific behavior and corrected for it. Subsequently, we developed a method to identify ChIP-enriched DNA fragments. We termed it physical model for tiling array analysis (PMT). We applied PMT to the data of ChIP-chip experiments interrogating chromosome 21 and 22 of the human genome for binding of the TFs MYC, SP1 and P53. Almost all regions recovered by PMT showed evidence for sequence-specific binding of the TFs

Temperature response of denitrification and anammox reveals the adaptation of microbial communities to in situ temperatures in permeable marine sediments that span 50° in latitude

Despite decades of research on the physiology and biochemistry of nitrate/nitrite-respiring microorganisms, little is known regarding their metabolic response to temperature, especially under in situ conditions. The temperature regulation of microbial communities that mediate anammox and denitrification was investigated in near shore permeable sediments at polar, temperate, and subtropical sites with annual mean temperatures ranging from -5 to 23 degrees C. Total N-2 production rates were determined using the isotope pairing technique in intact core incubations under diffusive and simulated advection conditions and ranged from 2 to 359 mu mol N m(-2) d(-1). For the majority of sites studied, N-2 removal was 2-7 times more rapid under simulated advective flow conditions. Anammox comprised 6-14% of total N-2 production at temperate and polar sites and was not detected at the subtropical site. Potential rates of denitrification and anammox were determined in anaerobic slurries in a temperature gradient block incubator across a temperature range of -1 degrees C to 42 degrees C. The highest optimum temperature (T-opt) for denitrification was 36 degrees C and was observed in subtropical sediments, while the lowest T-opt of 21 degrees C was observed at the polar site. Seasonal variation in the T-opt was observed at the temperate site with values of 26 and 34 degrees C in winter and summer, respectively. The T-opt values for anammox were 9 and 26 degrees C at the polar and temperate sites, respectively. The results demonstrate adaptation of denitrifying communities to in situ temperatures in permeable marine sediments across a wide range of temperatures, whereas marine anammox bacteria may be predominately psychrophilic to psychrotolerant. The adaptation of microbial communities to in situ temperatures suggests that the relationship between temperature and rates of N removal is highly dependent on community structure

Star Polymer-Drug Conjugates with pH-Controlled Drug Release and Carrier Degradation

In this study, we describe the design, synthesis, and physicochemical and preliminary biological characteristics of new biodegradable, high-molecular-weight (HMW) drug delivery systems with star-like architectures bearing the cytotoxic drug doxorubicin (DOX) attached by a hydrazone bond-containing spacer. The star polymers were synthesized by grafting semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers on a 2,2-bis(hydroxymethyl)propionic acid- (bis-MPA-) based polyester dendritic core. The molecular weight of the star polymers ranged from 280 to 450 000 g/mol and could be adjusted by proper selection of the bis-MPA dendrimer generation and by considering the polymer to dendrimer molar ratio. The biodegradation of the polymer conjugates is based on the spontaneous slow hydrolysis of the dendritic core in neutral physiological conditions. Hydrazone spacers in the conjugates were fairly stable at neutral pH (7.4) mimicking blood stream conditions, and DOX was released from the conjugates under mild acidic conditions simulating the tumor cell microenvironment in endosomes and lysosomes (pH 5). Finally, we have shown the significant in vitro cytotoxicity of the star polymer-DOX conjugate on selected cancer cell lines with IC50 values almost comparable with that of the free drug and higher than that observed for a linear polymer-DOX conjugate with much lower molecular weight

On Linear Algebraic Representation of Time-span and Prolongational Trees

In constructive music theory, such as Schenkerian analysis and the Generative Theory of Tonal Music (GTTM), the hierarchical importance of pitch events is conveniently represented by a tree structure. Although a tree is easy to recognize and has high visibility, such an intuitive representation can hardly be treated in mathematical formalization. Especially in GTTM, the conjunction height of two branches is often arbitrary, contrary to the notion of hierarchy. Since a tree is a kind of graph, and a graph is often represented by a matrix, we show the linear algebraic representation of trees, specifying conjunction heights. Thereafter, we explain the ‘reachability’ between pitch events (corresponding to information about reduction) by the multiplication of matrices. In addition we discuss multiplication with vectors representing a sequence of harmonic functions, and suggest the notion of stability. Finally, we discuss operations between matrices to model compositional processes with simple algebraic operations

A Large Hadron Electron Collider at CERN

This document provides a brief overview of the recently published report on the design of the Large Hadron Electron Collider (LHeC), which comprises its physics programme, accelerator physics, technology and main detector concepts. The LHeC exploits and develops challenging, though principally existing, accelerator and detector technologies. This summary is complemented by brief illustrations of some of the highlights of the physics programme, which relies on a vastly extended kinematic range, luminosity and unprecedented precision in deep inelastic scattering. Illustrations are provided regarding high precision QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed to run synchronously with the LHC in the twenties and to achieve an integrated luminosity of O(100) fb$^{-1}$. It will become the cleanest high resolution microscope of mankind and will substantially extend as well as complement the investigation of the physics of the TeV energy scale, which has been enabled by the LHC

The effect of tidal forcing on biogeochemical processes in intertidal salt marsh sediments

<p>Abstract</p> <p>Background</p> <p>Early diagenetic processes involved in natural organic matter (NOM) oxidation in marine sediments have been for the most part characterized after collecting sediment cores and extracting porewaters. These techniques have proven useful for deep-sea sediments where biogeochemical processes are limited to aerobic respiration, denitrification, and manganese reduction and span over several centimeters. In coastal marine sediments, however, the concentration of NOM is so high that the spatial resolution needed to characterize these processes cannot be achieved with conventional sampling techniques. In addition, coastal sediments are influenced by tidal forcing that likely affects the processes involved in carbon oxidation.</p> <p>Results</p> <p>In this study, we used in situ voltammetry to determine the role of tidal forcing on early diagenetic processes in intertidal salt marsh sediments. We compare ex situ measurements collected seasonally, in situ profiling measurements, and in situ time series collected at several depths in the sediment during tidal cycles at two distinct stations, a small perennial creek and a mud flat. Our results indicate that the tides coupled to the salt marsh topography drastically influence the distribution of redox geochemical species and may be responsible for local differences noted year-round in the same sediments. Monitoring wells deployed to observe the effects of the tides on the vertical component of porewater transport reveal that creek sediments, because of their confinements, are exposed to much higher hydrostatic pressure gradients than mud flats.</p> <p>Conclusion</p> <p>Our study indicates that iron reduction can be sustained in intertidal creek sediments by a combination of physical forcing and chemical oxidation, while intertidal mud flat sediments are mainly subject to sulfate reduction. These processes likely allow microbial iron reduction to be an important terminal electron accepting process in intertidal coastal sediments.</p

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4

Multiplicity Structure of the Hadronic Final State in Diffractive Deep-Inelastic Scattering at HERA

The multiplicity structure of the hadronic system X produced in deep-inelastic processes at HERA of the type ep -> eXY, where Y is a hadronic system with mass M_Y< 1.6 GeV and where the squared momentum transfer at the pY vertex, t, is limited to |t|<1 GeV^2, is studied as a function of the invariant mass M_X of the system X. Results are presented on multiplicity distributions and multiplicity moments, rapidity spectra and forward-backward correlations in the centre-of-mass system of X. The data are compared to results in e+e- annihilation, fixed-target lepton-nucleon collisions, hadro-produced diffractive final states and to non-diffractive hadron-hadron collisions. The comparison suggests a production mechanism of virtual photon dissociation which involves a mixture of partonic states and a significant gluon content. The data are well described by a model, based on a QCD-Regge analysis of the diffractive structure function, which assumes a large hard gluonic component of the colourless exchange at low Q^2. A model with soft colour interactions is also successful.Comment: 22 pages, 4 figures, submitted to Eur. Phys. J., error in first submission - omitted bibliograph