4,448 research outputs found
Condominium Conversions in the Bay Area
A Report to the Association of Bay Area Governments and the Department of City and Regional Planning in Partial Fulfillment of the Requirements for the Degree of Master of City Plannin
Archaeal DNA Polymerase-B as a DNA Template Guardian: Links between Polymerases and Base/Alternative Excision Repair Enzymes in Handling the Deaminated Bases Uracil and Hypoxanthine
In Archaea repair of uracil and hypoxanthine, which arise by deamination of cytosine and adenine, respectively, is initiated by three enzymes: Uracil-DNA-glycosylase (UDG, which recognises uracil); Endonuclease V (EndoV, which recognises hypoxanthine); and Endonuclease Q (EndoQ), (which recognises both uracil and hypoxanthine). Two archaeal DNA polymerases, Pol-B and Pol-D, are inhibited by deaminated bases in template strands, a feature unique to this domain. Thus the three repair enzymes and the two polymerases show overlapping specificity for uracil and hypoxanthine. Here it is demonstrated that binding of Pol-D to primer-templates containing deaminated bases inhibits the activity of UDG, EndoV, and EndoQ. Similarly Pol-B almost completely turns off EndoQ, extending earlier work that demonstrated that Pol-B reduces catalysis by UDG and EndoV. Pol-B was observed to be a more potent inhibitor of the enzymes compared to Pol-D. Although Pol-D is directly inhibited by template strand uracil, the presence of Pol-B further suppresses any residual activity of Pol-D, to near-zero levels. The results are compatible with Pol-D acting as the replicative polymerase and Pol-B functioning primarily as a guardian preventing deaminated base-induced DNA mutations
Matrix Big Brunch
Following the holographic description of linear dilaton null Cosmologies with
a Big Bang in terms of Matrix String Theory put forward by Craps, Sethi and
Verlinde, we propose an extended background describing a Universe including
both Big Bang and Big Crunch singularities. This belongs to a class of exact
string backgrounds and is perturbative in the string coupling far away from the
singularities, both of which can be resolved using Matrix String Theory. We
provide a simple theory capable of describing the complete evolution of this
closed Universe.Comment: 15 pages, no figures. References adde
Winding String Condensation and Noncommutative Deformation of Spacelike Singularity
In a previous paper (hep-th/0509067) using matrix model, we showed that
closed string tachyons can resolve spacelike singularity in one particular
class of Misner space (with anti-periodic boundary conditions for fermions
around the spatial circle). In this note, we show that for Misner space without
closed string tachyons, there also exists a mechanism to resolve the
singularity in the context of the matrix model, namely cosmological winding
string production. We show that here space and time also become noncommutative
due to these winding strings. Employing optical theorem, we study the bulk
boundary coupling by calculating the four-open-string cylinder amplitudes.Comment: 16 pages, no figures, harvmac; references added; added a section of
discussion on disk and cylinder amplitude
Effective Dynamics of the Matrix Big Bang
We study the leading quantum effects in the recently introduced Matrix Big
Bang model. This amounts to a study of supersymmetric Yang-Mills theory
compactified on the Milne orbifold. We find a one-loop potential that is
attractive near the Big Bang. Surprisingly, the potential decays very rapidly
at late times, where it appears to be generated by D-brane effects. Usually,
general covariance constrains the form of any effective action generated by
renormalization group flow. However, the form of our one-loop potential seems
to violate these constraints in a manner that suggests a connection between the
cosmological singularity and long wavelength, late time physics.Comment: 22 pages, LaTeX; some minor changes; an improved discussion of the
potentia
Cosmologies with Null Singularities and their Gauge Theory Duals
We investigate backgrounds of Type IIB string theory with null singularities
and their duals proposed in hep-th/0602107. The dual theory is a deformed N=4
Yang-Mills theory in 3+1 dimensions with couplings dependent on a light-like
direction. We concentrate on backgrounds which become AdS_5 x S^5 at early and
late times and where the string coupling is bounded, vanishing at the
singularity. Our main conclusion is that in these cases the dual gauge theory
is nonsingular. We show this by arguing that there exists a complete set of
gauge invariant observables in the dual gauge theory whose correlation
functions are nonsingular at all times. The two-point correlator for some
operators calculated in the gauge theory does not agree with the result from
the bulk supergravity solution. However, the bulk calculation is invalid near
the singularity where corrections to the supergravity approximation become
important. We also obtain pp-waves which are suitable Penrose limits of this
general class of solutions, and construct the Matrix Membrane theory which
describes these pp-wave backgrounds.Comment: 43 pages REVTeX and AMSLaTeX. v2: references adde
FUCA1 is induced by wild-type p53 and expressed at different levels in thyroid cancers depending on p53 status
Fucose residues of cell surface glycans, which play important roles in growth, invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by α-L-fucosidases (FUCAs). By the differential display method, we isolated a 3' non-coding region of α-L-fucosidase-1 (FUCA1) (a gene coding for the lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature-sensitive p53 mutant at the permissive temperature. By microarray analyses of thyroid cancer biopsy samples, FUCA1 RNA expression levels were found to be lower in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary thyroid cancer samples (PTCs) and in normal thyroid tissues. Since most ATCs were reported to carry the mutated form of p53, while PTCs carry mostly the wild-type form of p53, it is likely that FUCA1 expression levels are regulated, at least in part, by the p53 status in thyroid cancers. In order to better understand the role played by FUCA genes in thyroid tumorigenesis, we examined the clonogenic potential in vitro of thyroid cell lines transfected with either FUCA1 or FUCA2 (the latter gene coding for a secreted, non-lysosomal enzyme). We found that α-L-fucosidases did not suppress grossly cell growth. Contrary to what we observed with the expression of FUCA1, the FUT8 expression levels were found high in ATCsbut lower in PTCs and normal thyroid tissues. Taken together, these results suggest the possibility that the higher fucose levels on cell surface glycans of aggressive ATCs, compared to those of less aggressive PTCs, may be at least in part responsible for the more aggressive and metastatic phenotype of ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely related in these two types of cancers. Fucose residues of cell surface glycans, which play important roles in growth, invasion and metastasis, are added by fucosyltransferases (FUTs) and removed by α-L-fucosidases (FUCAs). By the differential display method, we isolated a 3' non-coding region of α-L-fucosidase-1 (FUCA1) (a gene coding for the lysosomal fucosidase-1 enzyme) as a wild-type p53-inducible gene: 18S and 20S FUCA1 mRNA species were induced in Saos-2 cells transfected with a temperature-sensitive p53 mutant at the permissive temperature. By microarray analyses of thyroid cancer biopsy samples, FUCA1 RNA expression levels were found to be lower in anaplastic thyroid cancer samples (ATCs), while they were higher in papillary thyroid cancer samples (PTCs) and in normal thyroid tissues. Since most ATCs were reported to carry the mutated form of p53, while PTCs carry mostly the wild-type form of p53, it is likely that FUCA1 expression levels are regulated, at least in part, by the p53 status in thyroid cancers. In order to better understand the role played by FUCA genes in thyroid tumorigenesis, we examined the clonogenic potential in vitro of thyroid cell lines transfected with either FUCA1 or FUCA2 (the latter gene coding for a secreted, non-lysosomal enzyme). We found that α-L-fucosidases did not suppress grossly cell growth. Contrary to what we observed with the expression of FUCA1, the FUT8 expression levels were found high in ATCs but lower in PTCs and normal thyroid tissues. Taken together, these results suggest the possibility that the higher fucose levels on cell surface glycans of aggressive ATCs, compared to those of less aggressive PTCs, may be at least in part responsible for the more aggressive and metastatic phenotype of ATCs compared to PTCs, as the expression levels of FUCA1 and FUT8 were inversely related in these two types of cancers
Novel inhibition of archaeal family-D DNA polymerase by uracil.
International audienceArchaeal family-D DNA polymerase is inhibited by the presence of uracil in DNA template strands. When the enzyme encounters uracil, following three parameters change: DNA binding increases roughly 2-fold, the rate of polymerization slows by a factor of â 5 and 3'-5' proof-reading exonuclease activity is stimulated by a factor of â 2. Together these changes result in a significant decrease in polymerization activity and a reduction in net DNA synthesis. Pol D appears to interact with template strand uracil irrespective of its distance ahead of the replication fork. Polymerization does not stop at a defined location relative to uracil, rather a general decrease in DNA synthesis is observed. 'Trans' inhibition, the slowing of Pol D by uracil on a DNA strand not being replicated is also observed. It is proposed that Pol D is able to interact with uracil by looping out the single-stranded template, allowing simultaneous contact of both the base and the primer-template junction to give a polymerase-DNA complex with diminished extension ability
[O III] and X-ray Properties of a Complete Sample of Hard X-ray Selected AGNs in the Local Universe
We study the correlation between the [O III] and X-ray
luminosities of local Active Galactic Nuclei (AGNs), using a complete, hard
X-ray ( keV) selected sample in the Swift/BAT 9-month catalog. From our
optical spectroscopic observations at the South African Astronomical
Observatory and the literature, a catalog of [O III] line flux
for all 103 AGNs at Galactic latitudes of is complied.
Significant correlations with intrinsic X-ray luminosity () are
found both for observed () and extinction-corrected () luminosities, separately for X-ray unabsorbed and absorbed
AGNs. We obtain the regression form of and from the whole sample. The absorbed AGNs with low
(0.5\%) scattering fractions in soft X-rays show on average smaller and ratios than the
other absorbed AGNs, while those in edge-on host galaxies do not. These results
suggest that a significant fraction of this population are buried in tori with
small opening angles. By using these vs.
correlations, the X-ray luminosity function of local AGNs (including Compton
thick AGNs) in a standard population synthesis model gives much better
agreement with the [O III] luminosity function derived from the
Sloan Digital Sky Survey than previously reported. This confirms that hard
X-ray observations are a very powerful tool to find AGNs with high
completeness.Comment: 14 pages including 11 figures and 3 tables, accepted for publication
in ApJ. In this manuscript, the observed 14-195 keV luminosities in Table 1
have been corrected to be exactly the same as in the original Swift/BAT
9-month catalog. Accordingly, Figures 2(a) and 3(a) and a part of Tables 2
and 3 have been updated. The changes from the previous version are small and
do not affect the tex
Applying Latent Class Analysis on Cancer Registry Data to Identify and Compare Health Disparity Profiles in Colorectal Cancer Surgical Treatment Delay
Context: Colorectal cancer (CRC) surgical treatment delay (TD) has been associated with mortality and morbidity; however, disparities by TD profiles are unknown. Objectives: This study aimed to identify CRC patient profiles of surgical TD while accounting for differences in sociodemographic, health insurance, and geographic characteristics. Design: We used latent class analysis (LCA) on 2005-2015 Tennessee Cancer Registry data of CRC patients and observed indicators that included sex/gender, age at diagnosis, marital status (single/married/divorced/widowed), race (White/Black/other), health insurance type, and geographic residence (non-Appalachian/Appalachian). Setting: The state of Tennessee in the United States that included both Appalachian and non-Appalachian counties. Participants: Adult (18 years or older) CRC patients (N = 35 412) who were diagnosed and surgically treated for in situ (n = 1286) and malignant CRC (n = 34 126). Main Outcome Measure: The distal outcome of TD was categorized as 30 days or less and more than 30 days from diagnosis to surgical treatment. Results: Our LCA identified a 4-class solution and a 3-class solution for in situ and malignant profiles, respectively. The highest in situ CRC patient risk profile was female, White, aged 75 to 84 years, widowed, and used public health insurance when compared with respective profiles. The highest malignant CRC patient risk profile was male, Black, both single/never married and divorced/separated, resided in non-Appalachian county, and used public health insurance when compared with respective profiles. The highest risk profiles of in situ and malignant patients had a TD likelihood of 19.3% and 29.4%, respectively. Conclusions: While our findings are not meant for diagnostic purposes, we found that Blacks had lower TD with in situ CRC. The opposite was found in the malignant profiles where Blacks had the highest TD. Although TD is not a definitive marker of survival, we observed that non-Appalachian underserved/underrepresented groups were overrepresented in the highest TD profiles. The observed disparities could be indicative of intervenable risk
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