DNA mismatch recognition and binding in human cells has been thought to be mediated by the hMSH2 protein. Here it is shown that the mismatch-binding factor consists of two distinct proteins, the ...100-kilodalton hMSH2 and a 160-kilodalton polypeptide, GTBP (for G/T binding protein). Sequence analysis identified GTBP as a new member of the MutS homolog family. Both proteins are required for mismatch-specific binding, a result consistent with the finding that tumor-derived cell lines devoid of either protein are also devoid of mismatch-binding activity.
A detailed investigation of the Raman “free” OH stretching band (3600–3650 cm
−
1
) of liquid alcohols has been performed. Raman spectra of pure liquids 1-octanol, 2-octanol and
tert-butanol have ...been analyzed as a function of temperature. Relevant spectral features have been consistently explained taking into account the concomitant effect of both rotational isomerism and hydrogen bonding. Important indications on the alcoholic liquid structure have been obtained following spectral modifications induced by the apolar 2,2-dimethylbutane solvent on the liquid
tert-butanol. Further, the Raman “free” OH stretching band has been employed to explore structural properties of the
tert-butanol/water system in the alcohol-rich region. The deduced hydration mechanism initially involves interaction of water molecules with
tert-butanol monomers.
We report on the first search for electron-muon lepton flavor violation (LFV) in the decay of a b quark and b antiquark bound state. We look for the LFV decay Υ(3S)→e±μ∓ in a sample of 118 million ...Υ(3S) mesons from 27 fb-1 of data collected with the BABAR detector at the SLAC PEP-II e+e- collider operating with a 10.36 GeV center-of-mass energy. No evidence for a signal is found, and we set a limit on the branching fraction BΥ(3S)→e±μ∓<3.6×10-7 at 90% C. L. This result can be interpreted as a limit ΛNP/gNP2>80 TeV on the energy scale ΛNP divided by the coupling-squared gNP2 of relevant new physics (NP).
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A panel of vectors was constructed to encode carcinoembryonic antigen (CEA) fused at its C-terminal end to various polypeptides, so as to compare their immunogenicity by plasmid DNA immunization and ...adenovirus injection in wild-type and CEA transgenic (CEA.tg) mice. Fusions between CEA and the minimized domain of tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were identified as highly immunogenic and elicited significant CEA-specific antibody and CD8+ T cell responses. CEA.tg mice were protected from tumor growth on challenge with MC38-CEA tumor cells only when immunized with repeated injections of plasmid pV1J/CEA-DOM followed by Ad/CEA-DOM. Depletion of T-regulatory cells resulted in an increased immune response and antitumor effect with DNA plus adenovirus immunization. In addition, this protective effect was abrogated if the NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor challenge. Passive transfer studies demonstrated that CD4+ and CD8+ T cells and antibodies contributed to the antitumor effect, thus suggesting that a genetic vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused to immunoenhancing sequences augments CEA-specific immune responses and effectively protects from tumor development.
In the design of the Silicon Vertex Tracker for the high luminosity SuperB collider, very challenging requirements are set by physics and background conditions on its innermost Layer0: small radius ...(about 1.5cm), resolution of 10–15μm in both coordinates, low material budget <1%X0, and the ability to withstand a background hit rate of several tens of MHz/cm2. Thanks to an intense R&D program the development of Deep NWell CMOS MAPS (with the ST Microelectronics 130nm process) has reached a good level of maturity and allowed for the first time the implementation of thin CMOS sensors with similar functionalities as in hybrid pixels, such as pixel-level sparsification and fast time stamping. Further MAPS performance improvements are currently under investigation with two different approaches: the INMAPS CMOS process, featuring a quadruple well and a high resistivity substrate, and 3D CMOS MAPS, realized with vertical integration technology. In both cases specific features of the processes chosen can improve charge collection efficiency, with respect to a standard DNW MAPS design, and allow to implement a more complex in-pixel logic in order to develop a faster readout architecture. Prototypes of MAPS matrix, suitable for application in the SuperB Layer0, have been realized with the INMAPS 180nm process and the 130nm Chartered/Tezzaron 3D process and results of their characterization will be presented in this paper.
Mutations of GTBP in Genetically Unstable Cells Papadopoulos, Nickolas; Nicolaides, Nicholas C.; Liu, Bo ...
Science (American Association for the Advancement of Science),
06/1995, Volume:
268, Issue:
5219
Journal Article
Peer reviewed
The molecular defects responsible for tumor cell hypermutability in humans have not yet been fully identified. Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 ...megabase of the related hMSH2 gene on chromosome 2 and was found to be inactivated in three hypermutable cell lines. Unlike cells defective in other mismatch repair genes, which display widespread alterations in mononucleotide, dinucleotide, and other simple repeated sequences, the GTBP-deficient cells showed alterations primarily in mononucleotide tracts. These results suggest that GTBP is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype.
Adenovirus (Ad) and adeno-associated virus (AAV) have attractive and complementary properties that can be exploited for gene transfer purposes. Ad vectors are probably the most efficient vehicles to ...deliver foreign genes both in vitro and in vivo. AAV exhibits the unique ability to establish latency by efficiently integrating at a specific locus of human chromosome 19 (AAVS1). Two viral elements are necessary for the integration at AAVS1: Rep68/78 and the inverted terminal repeats (AAV-ITRs). In this study, we report the development of two helper-dependent adenoviral (HD) vectors, one carrying the Rep78 gene, the other an AAV-ITR-flanked transgene. Although Rep proteins have been demonstrated to interfere with Ad replication, HD Rep78 vector was successfully amplified on serial passages in 293CRE4 cells with a yield of 50-100 transducing units per cell. DNA integration at the AAVS1 site also was demonstrated in hepatoma cells coinfected with the HD-expressing Rep78 and with the second HD vector carrying a transgene flanked by AAV-ITRs. The high transduction efficiency, large cloning capacity, and high titer of the HD, combined with the site-specific integration machinery provided by AAV-derived components, make the Ad/AAV hybrid viruses a promising vehicle for gene therapy.
The front-end chip of the SuperB SVT detector Giorgi, F.; Comotti, D.; Manghisoni, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2013, Volume:
718
Journal Article
Peer reviewed
Open access
The asymmetric e+e− collider SuperB is designed to deliver a high luminosity, greater than 1036cm−2s−1, with moderate beam currents and a reduced center of mass boost with respect to earlier ...B-Factories. The innermost detector is the Silicon Vertex Tracker which is made of 5 layers of double sided silicon strip sensors plus a layer 0, that can be equipped with short striplets detectors in a first phase of the experiment. In order to achieve an overall track reconstruction efficiency above 98% it is crucial to optimize both analog and digital readout circuits. The readout architecture being developed for the front-end chips will be able to cope with the very high rates expected in the first layer. The digital readout will be optimized to be fully efficient for hit rates up to 2MHz/strip, including large margins on the maximum expected background rates, but can potentially accommodate higher rates with a proper tuning of the buffer depth. The readout is based on a triggered architecture where each of the 128 strip channel is provided with a dedicated digital buffer. Each buffer collects the digitized charge information by means of a 4-bit TOT, storing it in conjunction with the related time stamp. The depth of buffers was dimensioned considering the expected trigger latency and hit rate including suitable safety margins. Every buffer is connected to a highly parallelized circuit handling the trigger logic, rejecting expired data in the buffers and channeling the parallel stream of triggered hits to the common output of the chip. The presented architecture has been modeled by HDL language and investigated with a Monte Carlo hit generator emulating the analog front-end behavior. The simulations showed that even applying the highest stressing conditions, about 2MHz per strip, the efficiency of the digital readout remained above 99.8%.
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