Is the whole greater than the sum of its parts? De novo assembly strategies for bacterial genomes based on paired-end sequencing

Number of misassemblies for different assembly strategies. Number of misassemblies for the de novo assembly results for E. coli DH1 and S. Parasanguinis FW213 are shown together with their standard errors of the mean. Group A [PE] and Group A [SE] represent all reads assembled as paired-end reads and single end reads, respectively. Group A [PE + SE] represents all the non-overlapped paired-end reads assembled together with merged reads. Group M [PE] and Group M [SE] represent Group M reads assembled as paired-end reads and single end reads, respectively. The numbers of misassemblies fluctuate a lot when depths of read number are low and gradually decreases until they reach a steady number. The paired-end reads (Group A [PE] and Group M [PE]) in S. Parasanguinis FW213 gave the lowest number of misassemblies when depths of read number are high. (TIFF 669 kb

Exploring the Mechanism Responsible for Cellulase Thermostability by Structure-Guided Recombination

Cellulases from Bacillus and Geobacillus bacteria are potentially useful in the biofuel and animal feed industries. One of the unique characteristics of these enzymes is that they are usually quite thermostable. We previously identified a cellulase, GsCelA, from thermophilic Geobacillus sp. 70PC53, which is much more thermostable than its Bacillus homolog, BsCel5A. Thus, these two cellulases provide a pair of structures ideal for investigating the mechanism regarding how these cellulases can retain activity at high temperature. In the present study, we applied the SCHEMA non-contiguous recombination algorithm as a novel tool, which assigns protein sequences into blocks for domain swapping in a way that lessens structural disruption, to generate a set of chimeric proteins derived from the recombination of GsCelA and BsCel5A. Analyzing the activity and thermostability of this designed library set, which requires only a limited number of chimeras by SCHEMA calculations, revealed that one of the blocks may contribute to the higher thermostability of GsCelA. When tested against swollen Avicel, the highly thermostable chimeric cellulase C10 containing this block showed significantly higher activity (22%-43%) and higher thermostability compared to the parental enzymes. With further structural determinations and mutagenesis analyses, a 3_(10) helix was identified as being responsible for the improved thermostability of this block. Furthermore, in the presence of ionic calcium and crown ether (CR), the chimeric C10 was found to retain 40% residual activity even after heat treatment at 90°C. Combining crystal structure determinations and structure-guided SCHEMA recombination, we have determined the mechanism responsible for the high thermostability of GsCelA, and generated a novel recombinant enzyme with significantly higher activity

Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks

Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents. Transcriptome profiling and functional assays implicate contributions from functional voltage-gated Ca^(2+) channels (VGCCs), Connexin-43 based gap junctions, and Ca^(2+) release activated Ca^(2+) (CRAC) channels. 4-Dimensional Ca^(2+) imaging reveals that the Sonic hedgehog-responsive mesenchymal cells display synchronized Ca^(2+) oscillations, which expand progressively in area during feather elongation. Inhibiting VGCCs, gap junctions, or Sonic hedgehog signaling alters the mesenchymal Ca^(2+) landscape, cell movement patterns and feather bud elongation. Ca^(2+) oscillations induced by cyclic activation of opto-cCRAC channels enhance feather bud elongation. Functional disruption experiments and promoter analysis implicate synergistic Hedgehog and WNT/β-Catenin signaling in activating Connexin-43 expression, establishing gap junction networks synchronizing the Ca^(2+) profile among cells, thereby coordinating cell movement patterns

Fusion of Color Doppler and Magnetic Resonance Images of the Heart

This study was designed to establish and analyze color Doppler and magnetic resonance fusion images of the heart, an approach for simultaneous testing of cardiac pathological alterations, performance, and hemodynamics. Ten volunteers were tested in this study. The echocardiographic images were produced by Philips IE33 system and the magnetic resonance images were generated from Philips 3.0-T system. The fusion application was implemented on MATLAB platform utilizing image processing technology. The fusion image was generated from the following steps: (1) color Doppler blood flow segmentation, (2) image registration of color Doppler and magnetic resonance imaging, and (3) image fusion of different image types. The fusion images of color Doppler blood flow and magnetic resonance images were implemented by MATLAB programming in our laboratory. Images and videos were displayed and saved as AVI and JPG. The present study shows that the method we have developed can be used to fuse color flow Doppler and magnetic resonance images of the heart. We believe that the method has the potential to: fill in information missing from the ultrasound or MRI alone, show structures outside the field of view of the ultrasound through MR imaging, and obtain complementary information through the fusion of the two imaging methods (structure from MRI and function from ultrasound)

Central nervous system rather than immune cell-derived BDNF mediates axonal protective effects early in autoimmune demyelination

Brain-derived neurotrophic factor (BDNF) is involved in neuronal and glial development and survival. While neurons and astrocytes are its main cellular source in the central nervous system (CNS), bioactive BDNF is also expressed in immune cells and in lesions of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Previous data revealed that BDNF exerts neuroprotective effects in myelin oligodendrocyte glycoprotein-induced EAE. Using a conditional knock-out model with inducible deletion of BDNF, we here show that clinical symptoms and structural damage are increased when BDNF is absent during the initiation phase of clinical EAE. In contrast, deletion of BDNF later in the disease course of EAE did not result in significant changes, either in the disease course or in axonal integrity. Bone marrow chimeras revealed that the deletion of BDNF in the CNS alone, with no deletion of BDNF in the infiltrating immune cells, was sufficient for the observed effects. Finally, the therapeutic effect of glatiramer acetate, a well-characterized disease-modifying drug with the potential to modulate BDNF expression, was partially reversed in mice in which BDNF was deleted shortly before the onset of disease. In summary, our data argue for an early window of therapeutic opportunity where modulation of BDNF may exert neuroprotective effects in experimental autoimmune demyelination

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Dynamic model of basic oxygen steelmaking process based on multi-zone reaction kinetics : modelling of manganese removal

In the earlier work, a dynamic model for the BOF process based on the multi-zone reaction kinetics has been developed. In the preceding part, the mechanism of manganese transfer in three reactive zones of the converter has been analyzed. This study identifies that temperature at the slag-metal reaction interface plays a major role in the Mn reaction kinetics and thus a mathematical treatment to evaluate temperature at each reaction interface has been successfully employed in the rate calculation. The Mn removal rate obtained from different zones of the converter predicts that the first stage of the blow is dominated by the oxidation of Mn at the jet impact zone, albeit some additional Mn refining has been observed as a result of the oxidation of metal droplets in emulsion phase. The mathematical model predicts that the reversion of Mn from slag to metal primarily takes place at the metal droplet in the emulsion due to an excessive increase in slag-metal interface temperature during the middle stage of blowing. In the final stage of the blow, the competition between simultaneous reactions in jet impact and emulsion zone controls the direction of mass flow of manganese. Further, the model prediction shows that the Mn refining in the emulsion is a strong function of droplet diameter and the residence time. Smaller sized droplets approach equilibrium quickly and thus contribute to a significant Mn conversion between slag and metal compared to the larger sized ones. The overall model prediction for Mn in the hot metal has been found to be in good agreement with two sets of different size top blowing converter data reported in the literature

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO