Impaired Translesion Synthesis in Xeroderma Pigmentosum Variant Extracts

Xeroderma pigmentosum variant (XPV) cells are characterized by a cellular defect in the ability to synthesize intact daughter DNA strands on damaged templates. Molecular mechanisms that facilitate replication fork progression on damaged DNA in normal cells are not well defined. In this study, we used single-stranded plasmid molecules containing a single N-2-acetylaminofluorene (AAF) adduct to analyze translesion synthesis (TLS) catalyzed by extracts of either normal or XPV primary skin fibroblasts. In one of the substrates, the single AAF adduct was located at the 3' end of a run of three guanines that was previously shown to induce deletion of one G by a slippage mechanism. Primer extension reactions performed by normal cellular extracts from four different individuals produced the same distinct pattern of TLS, with over 80% of the products resulting from the elongation of a slipped intermediate and the remaining 20% resulting from a nonslipped intermediate. In contrast, with cellular extracts from five different XPV patients, the TLS reaction was strongly reduced, yielding only low amounts of TLS via the nonslipped intermediate. With our second substrate, in which the AAF adduct was located at the first G in the run, thus preventing slippage from occurring, we confirmed that normal extracts were able to perform TLS 10-fold more efficiently than XPV extracts. These data demonstrate unequivocally that the defect in XPV cells resides in translesion synthesis independently of the slippage proces

Mutagenicity of Acridines in a Reversion Assay Based on Tetracycline Resistance in Plasmid pBR322 in Escherichia Coli

The mutagenicity of a series of acridine compounds was studied in an assay based on the reversion of mutations in the tetracycline-resistance gene (tet) of plasmid pBR322 in Escherichia coli. Mutations that restore the tetracycline-resistant phenotype were detected in tetracycline-sensitive strains carrying mutant plasmids. Mutations that revert by +2, +1, −1, and −2 frameshift mutations and by base-pair substitutions were used to analyze the mutagenicity of two simple acridines, two acridine mustards, and a nitroacridine. The simple acridines (9-aminoacridine and quinacrine) effectively induced −1 frameshifts and weakly induced +1 frameshifts. The acridine mustards (quinacrine mustard and ICR-191) were more potent inducers of −1 and +1 frameshifts than the simple acridines. Reactive acridines, including both the mustards and the nitroacridine Entozon, were effective inducers of −2 frameshifts but the simple acridines were not. The two classes of reactive acridines differed from one another, in that the mustards were better inducers of +1 frameshifts than Entozon, whereas Entozon was a particularly potent inducer of −2 frameshifts. None of the compounds induced +2 frameshifts, and the induction of base-pair substitutions was negligible. These results confirm and extend studies showing that adduct-forming acridines are stronger frameshift mutagens than simple intercalating acridines and that the acridines differ from one another not only in overall mutagenic potency but also in the prevalence of different classes of frameshift mutations

Optimal Eavesdropping in Quantum Cryptography. II. Quantum Circuit

It is shown that the optimum strategy of the eavesdropper, as described in the preceding paper, can be expressed in terms of a quantum circuit in a way which makes it obvious why certain parameters take on particular values, and why obtaining information in one basis gives rise to noise in the conjugate basis.Comment: 7 pages, 1 figure, Latex, the second part of quant-ph/970103

Kinematics of Metal-Poor Stars in the Galaxy. II. Proper Motions for a Large Non-Kinematically Selected Sample

We present a revised catalog of 2106 Galactic stars, selected without kinematic bias, and with available radial velocities, distance estimates, and metal abundances in the range 0.0 <= [Fe/H] <= -4.0. This update of the Beers and Sommer-Larsen (1995) catalog includes newly-derived homogeneous photometric distance estimates, revised radial velocities for a number of stars with recently obtained high-resolution spectra, and refined metallicities for stars originally identified in the HK objective-prism survey (which account for nearly half of the catalog) based on a recent re-calibration. A subset of 1258 stars in this catalog have available proper motions, based on measurements obtained with the Hipparcos astrometry satellite, or taken from the updated Astrographic Catalogue (AC 2000; second epoch positions from either the Hubble Space Telescope Guide Star Catalog or the Tycho Catalogue), the Yale/San Juan Southern Proper Motion (SPM) Catalog 2.0, and the Lick Northern Proper Motion (NPM1) Catalog. Our present catalog includes 388 RR Lyrae variables (182 of which are newly added), 38 variables of other types, and 1680 non-variables, with distances in the range 0.1 to 40 kpc.Comment: 31 pages, including 8 figures, to appear in AJ (June 2000), full paper with all figures embedded available at http://pluto.mtk.nao.ac.jp/people/chiba/preprint/halo4

One-and-a-half quantum de Finetti theorems

We prove a new kind of quantum de Finetti theorem for representations of the unitary group U(d). Consider a pure state that lies in the irreducible representation U_{mu+nu} for Young diagrams mu and nu. U_{mu+nu} is contained in the tensor product of U_mu and U_nu; let xi be the state obtained by tracing out U_nu. We show that xi is close to a convex combination of states Uv, where U is in U(d) and v is the highest weight vector in U_mu. When U_{mu+nu} is the symmetric representation, this yields the conventional quantum de Finetti theorem for symmetric states, and our method of proof gives near-optimal bounds for the approximation of xi by a convex combination of product states. For the class of symmetric Werner states, we give a second de Finetti-style theorem (our 'half' theorem); the de Finetti-approximation in this case takes a particularly simple form, involving only product states with a fixed spectrum. Our proof uses purely group theoretic methods, and makes a link with the shifted Schur functions. It also provides some useful examples, and gives some insight into the structure of the set of convex combinations of product states.Comment: 14 pages, 3 figures, v4: minor additions (including figures), published versio

In defense of the epistemic view of quantum states: a toy theory

We present a toy theory that is based on a simple principle: the number of questions about the physical state of a system that are answered must always be equal to the number that are unanswered in a state of maximal knowledge. A wide variety of quantum phenomena are found to have analogues within this toy theory. Such phenomena include: the noncommutativity of measurements, interference, the multiplicity of convex decompositions of a mixed state, the impossibility of discriminating nonorthogonal states, the impossibility of a universal state inverter, the distinction between bi-partite and tri-partite entanglement, the monogamy of pure entanglement, no cloning, no broadcasting, remote steering, teleportation, dense coding, mutually unbiased bases, and many others. The diversity and quality of these analogies is taken as evidence for the view that quantum states are states of incomplete knowledge rather than states of reality. A consideration of the phenomena that the toy theory fails to reproduce, notably, violations of Bell inequalities and the existence of a Kochen-Specker theorem, provides clues for how to proceed with this research program.Comment: 32 pages, REVTEX, based on a talk given at the Rob Clifton Memorial Conference, College Park, May 2003; v2: minor modifications throughout, updated reference

Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration

In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life1, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding microenvironment, or niche3. The activation of such stem cells is cyclic, involving periodic -catenin activity4, 5, 6, 7. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug delivery and stem cell engineering studies, because they highlight the acute need to differentiate supportive versus inhibitory regions in the host skin