1,639 research outputs found
Portrait of Samuel M. Jones
A sepia portrait of Samuel Milton Jones taken around 1900. Samuel "Golden Rule" Jones was a progressive businessman and owner of the Acme Sucker Rod Company. Jones was mayor of the City of Toledo at the time of this photograph from 1897 to the time of his death in 1904
Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization
The nuclear lamina is a meshwork of intermediate-type filament proteins (lamins) that lines the inner nuclear membrane. The lamina is proposed to be an important determinant of nuclear structure, but there has been little direct testing of this idea. To investigate lamina functions, we have characterized a novel lamin B1 mutant lacking the middle approximately 4/5 of its alpha-helical rod domain. Though retaining only 10 heptads of the rod, this mutant assembles into intermediate filament-like structures in vitro. When expressed in cultured cells, it concentrates in patches at the nuclear envelope. Concurrently, endogenous lamins shift from a uniform to a patchy distribution and lose their complete colocalization, and nuclei become highly lobulated. In vitro binding studies suggest that the internal rod region is important for heterotypic associations of lamin B1, which in turn are required for proper organization of the lamina. Accompanying the changes in lamina structure induced by expression of the mutant, nuclear pore complexes and integral membrane proteins of the inner membrane cluster, principally at the patches of endogenous lamins. Considered together, these data indicate that lamins play a major role in organizing other proteins in the nuclear envelope and in determining nuclear shape
Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina
PURPOSE: Kinetic studies of photoreceptor cell death in the retinal degeneration (rd1) mouse model suggest that photoreceptor degeneration could result from cumulative damage. Since alterations in glutamate metabolism have been described in different models of retinitis pigmentosa, we investigated in the present work whether changes in glutamate turnover occur in the degenerating rd1 retina and whether glutamate-mediated excitotoxic mechanisms may contribute to rod photoreceptor death in this model. METHODS: Free amino acid levels were quantified in rd1 and wild-type retinas using an amino acid analyzer selecting times corresponding to early, intermediate, and terminal phases of rod photoreceptor degeneration. Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of the glial L-glutamate/L-aspartate transporter GLAST, glutamine synthetase (GS), and vimentin, a marker for retinal glia, between rd1 and wild-type mouse retinas. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of both AMPA and kainate subtypes of ionotropic glutamate receptors, was then daily administered from postnatal day 3 (PN3) to PN21 to rd1 mice while control rd1 mice received only physiological saline solution (7 per treatment). At PN22, the respective numbers of surviving rods i
Crystal structure of the P pilus rod subunit PapA
P pili are important adhesive fibres involved in kidney infection by uropathogenic Escherichia coli strains. P pili are assembled by the conserved chaperone-usher pathway, which involves the PapD chaperone and the PapC usher. During pilus assembly, subunits are incorporated into the growing fiber via the donor-strand exchange (DSE) mechanism, whereby the chaperone's G(1) beta-strand that complements the incomplete immunoglobulin-fold of each subunit is displaced by the N-terminal extension (Nte) of an incoming subunit. P pili comprise a helical rod, a tip fibrillum, and an adhesin at the distal end. PapA is the rod subunit and is assembled into a superhelical right-handed structure. Here, we have solved the structure of a ternary complex of PapD bound to PapA through donor-strand complementation, itself bound to another PapA subunit through DSE. This structure provides insight into the structural basis of the DSE reaction involving this important pilus subunit. Using gel filtration chromatography and electron microscopy on a number of PapA Nte mutants, we establish that PapA differs in its mode of assembly compared with other Pap subunits, involving a much larger Nte that encompasses not only the DSE region of the Nte but also the region N-terminal to it
Atlas event production on the EGEE infrastructure
ATLAS is one of the four LHC (Large Hadron Collider) experiments at CERN, is devoted to study proton-proton and ion-ion collisions at 14TeV. ATLAS collaboration is composed of about 2000 scientists spread around the world. The activity of the experiment requirements for next year is of about 300TB of storage and a CPU power of about 13 Mski2sk, and is relying on GRID philosophy and EGEE infrastructure. Simulated events are distributed over EGEE by the Atlas production system. Data has to be processed and must be accessible by a huge number of scientists for analysis. The throughput of data for Atlas experiment is expected to be of 320 MB/s with an integrated amount of data per year of ~10Pb. The processing and storage need a distributed share of resources, spread worldwide and interconnected with GRID technologies as the requirements are so demanding for the LHC. In that sense event production is the way to produce, process and store data for analysis before the experiment startup, and is performed in a distributed way. Tasks are defined by physics coordinators and then are assigned to Computing Elements spread worldwide. Some of the jobs that build up the tasks need input data as well to produce new output, this means the jobs may need input from external sites and store remotely. For that reason sites are connected by File Transfer Service (FTS) channels that links the Storage Elements (SE) interface for each site. ATLAS is using the services provided by the EGEE middleware. Event simulation jobs are sent to the LCG (LHC Computing Grid) GRID by glite-WMS (Workload Management System) and Condor-G and using the dispatching tools of the CE's. Event simulation jobs perform the Data Management as well, request the inputs and stores the outputs on the desired SE's, file location and information is managed with distributed LCG File Catalogues (LFC). On the other hand, asymmetric file movement is performed by the ATLAS specific software on Distributed Data Management (DDM), which takes care of the file movement on top of the FTS services. Services which are causing problems are basically the Storage Elements, the system is strongly dependent on the inputs for the event simulation jobs and failing to retrieve it produces job failures, while failures in storing the outputs due to SE's instabilities leads to the loss of the CPU consumed by the job and the consequent failure. From the event simulation is expected that glite-WMS handles the jobs in a more reliable way, and concerning the CE's perhaps introduce different implementations that would have no scalability limitations. Certainly we hope new implementation of the SRM (Storage Resource Manager) interface that would solve stability problems mainly in the stage-in and stageout of the files needed and produced by the jobs respectively
Numerical Investigations of Coherent Structures in Axial Flow in Single Rod-Channel Geometry
In order to ramp up the conversion ratios and burn-up of nuclear reactors, it is inevitable to go to tightly packed fuel rods in the reactor. These nuclear reactors with tightly packed rod-bundles are characterized by interesting flow patterns, different from the ones encountered in regular channel and pipe flows. The correct prediction and control of the flow distribution is essential for the reactor design and safety assessment, and has been an active area of research in reactor thermal-hydraulics. Apart from the axial flow of coolant parallel to the rod bundles, there exists cross-flow between the sub-channels. The cross-flow promotes homogeneous enthalpy distribution and enhanced mixing between the coolant flowing in the sub-channels. Turbulent mixing is an important phenomenon, which influences the flow and temperature patterns in the rod bundles. Large-scale coherent structures along with transverse flow pulsations have been identified in the rod-rod and rod-wall gap regions. This large-scale structure has a quasi-periodic behavior and is considered an important factor for high mixing-rate. The aim of this work is to get a better understanding of the flow in a rod-bundle. This is done by performing numerical investigations on a simplified rod-channel geometry. The Unsteady Reynolds Averaged Navier Stokes equations are solved using the Computational Fluid Dynamics software OpenFOAM. Extensive benchmark and validation studies were done in order to determine the simulation technique that offers a good balance between computational cost and accuracy. The flow dynamics and the transport and mixing of a passive scalar due to the coherent structures are studied. Different turbulence models were used to study their effect on flow dynamics, and no major differences were observed. Following this, the computationally cheaper k-epsilon turbulence model with wall functions was chosen for the simulations. The time required for flow development in this geometry was significantly higher than that in regular turbulent channel or pipe flow. This led to different results than the ones observed in the experiments and in previous simulation results published in the literature. It was concluded that the flow in the experiments was not fully developed and that probably not enough time was used to allow flow development in the previous simulations. Our results indicate that the shear-layer becomes thinner and the number of structures decreased with flow development, which would explain the higher number of structures found in previous simulations. High values of velocity fluctuations and the kinetic energy due to these fluctuations indicated the presence of structures in the near-gap region. Large-scale three-dimensional counter-rotating sledge-shaped structures were observed via the flow visualization of resolved velocity. These structures were not only restricted to the gap region, but encompassed the entire flow domain. The high periodicity and stability of these structures indicate that they are not turbulence structures. The effect of gap-size on the coherent structures was studied, and this study suggested that the presence of more than one mechanism for the formation of these structures. A critical gap-size was obtained, at which the intensity of the structures has a maximum value, and a cut-off gap size was identified, at which a transition takes place between the two mechanisms. The coherent structures were found to play a significant role in both the transport and mixing of the passive scalar. The contribution were similar to that of the turbulent diffusion. The simulations indicate that the effect of the coherent structures on the transport and mixing of a passive scalar is of the same order of magnitude of the effect of the turbulent diffusion.Chemical EngineeringRadiation, Radionuclides & ReactorsApplied Science
Does GDNF exert its neuroprotective effects on photoreceptors in the rd1 retina through the glial glutamate transporter GLAST?
PURPOSE: We previously demonstrated that exogenous glial cell line-derived neurotrophic factor (GDNF) induces histological and functional protection of photoreceptors in the retinal degeneration (rd1) mouse model. The mechanisms underlying such neuroprotection remain elusive. In parallel to this work, we provided evidence for the occurrence of glutamate-mediated excitotoxic phenomena contributing to rod photoreceptor death in the rd1 retina in the companion paper. In the present study, we investigated whether, as demonstrated in other models, GDNF could exert its neuroprotective effect on photoreceptors through Muller glial cells (MGC) by promoting the expression of the glial L-glutamate/L-aspartate transporter (GLAST), an endogenous neuroprotective mechanism against glutamate-mediated excitotoxicity. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of GDNF receptors between rd1 and wild-type mouse retinas as well as between MGC and mixed retinal cell cultures. Recombinant GDNF was applied to pure MGC cultures, to rd1 retinal organ cultures and injected subretinally into rd1 mouse eyes. GLAST expression following GDNF treatment was measured by RT-PCR, immunoblotting and immunohistochemistry. Free glutamate and glutamine levels were quantified in rd1 retinas after GDNF or control treatment using an amino acid analyzer. RESULTS: mRNA expression studies of GDNF receptors, GFRalpha-1 and Ret, demonstrated that GDNF receptors were not exclusively expressed by the degenerating photoreceptor cells but mainly by MGC. Exogenous GDNF application to MGC cultures, rd1 mouse retinal explants and in vivo rd1 mouse retinas increased the expression of GLAST by 48% in retinal explants (p<0.005) and by 25% in vivo (p<0.0005). GLAST protein expression in MGC was particularly increased around degenerative photoreceptors. Free glutamate and glutamine levels in the rd1 retina were not significantly modified by exogenous GDNF. CONCLUSIONS: Our data suggest that, in the rd1 mouse retina, GDNF neuroprotective effect on photoreceptors can be mediated indirectly through the activation of MGC. We demonstrate that injection of recombinant GDNF enhances the expression of GLAST and more particularly around the degenerating photoreceptors. Since we failed to demonstrate that GDNF decreases free glutamate levels, we could not ascertain whether GDNF promoted photoreceptor-survival via an increase of glutamate uptake and, therefore, a change in glutamate distributio
Evolved Gas Analysis of Rigid-Rod Polymers
ABSTRACTThe rigid-rod polymer system poly(phenylenebenzobisthiazole), designated as PBZT, has considerable potential in materials engineering. The vacuum thermal behavior of this system and various substituted analogues, including methyl-, phenyl-, and benzothiazolyl-substituted members, has been studied using the combined techniques of thermogravimetry and mass spectroscopy (TG-MS).Primary volatile products identified from the PBZT series include H2S, HCN, CS2, NH3, C6H5CN, C6H4(CN)2, and HSCN. The presence of pendant groups such as methyl, phenyl, or benzothiazolyl results in the evolution of methane, benzene, or benzothiazole in low-temperature degradation processes. The relative abundance and temporal sequence of these gases which are evolved during slow heating in vacuum provide valuable information concerning thermal stability.The implications of the identification and study of evolved gases toward the understanding of the mechanisms of heat treating of rigid-rod polymer systems will be discussed.</jats:p
Protein-protein interactions leading to recruitment of the host DNA sliding clamp by the hyperthermophilic Sulfolobus islandicus rod- shaped virus 2
Viruses infecting hyperthermophilic archaea typically do not encode DNA polymerases, raising questions regarding their genome replication. Here, using a yeast two-hybrid approach, we have assessed interactions between proteins of Sulfolobus islandicus rod-shaped virus 2 (SIRV2) and the host-encoded proliferating cell nuclear antigen (PCNA), a key DNA replication protein in archaea. Five SIRV2 proteins were found to interact with PCNA, providing insights into the recruitment of host replisome for viral DNA replication.Peer reviewe
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