p53 in polyoma virus transformed REF52 cells

While cellular transformation by small DNA tumour viruses usually involves targeting the product of the p53 tumour suppressor gene by a virally encoded protein, none of the three polyoma virus (Py) specified T antigens have been observed to interact with p53. We show that primary mouse embryo fibroblasts and REF52 cells, which resemble primary cells in requiring co-operating oncogenes for transformation, cannot be transformed by the Py oncogene, middle T-antigen (PyMT), alone. These cells can be transformed by the complete Py early region, which encodes the Py large, middle and small T-antigens. We find that PyMT can transform rodent cells lacking a functional p53 protein (p53 null mouse embryo fibroblasts and DN-REF52 cells which contain a dominant negative p53). In Py transformed REF52 cells (Py-REF52) there is no significant accumulation of p53 protein, as opposed to SV40 transformed REF52 cells (SV-REF52) in which the amount of steady state p53 protein is elevated. However accumulation of p53 is observed following exposure of Py-REF52 cells to u.v. Treatment of Py-REF52 cells with X-rays results in a rapid increase in the levels of the p53-induced proteins p21/WAF1 and MDM2. In untransformed REF52 cells, X-irradiation causes p53 activation, which results in induction of both G1/S and G2/M blocks. In SV-REF52 and DN-REF52 cells, p53 abrogation results in the absence of both the G1/S and G2/M blocks. Only the absence of a G1/S block is observed in Py-REF52 cells exposed to X-irradiation. Together these results indicate that in contrast to most other DNA tumour viruses, Py does not appear to interfere with the DNA damage induced transactivation activities of the p53 protein but absence of a functional p53 protein can mediate transformation by the PyMT oncogene in the absence of other co-operating oncogenes. Possible modes of transformation by Py are discussed.     

Performance analysis of Drever-Hall laser frequency stabilizationusing a proportional+integral servo

In this paper, we derive analytical expressions for finite gain, finite bandwidth laser frequency locking systems. The common case of Drever-Hall (FM sideband) locking to a Fabry-Perot cavity is discussed, using a proportional+integral (PI) controller as an example. The effects of nonnegligible loop time-delay on stability are discussed, and an optimal design procedure for a frequency locking system is given     

Dyadic perfectionism as a predictor of relationship continuity and distress among college students.

This study examined the nature and impact of dyadic perfectionism over a 3-month interval within a sample of 116 college students who were currently involved in an intimate heterosexual relationship. Dyadic perfectionism scores were stable and correlated as expected with scores on concurrent measures of adult attachment orientations and relationship satisfaction. Logistic regression analyses revealed that, controlling for initial commitment status and adult attachment orientations, Time 1 dyadic perfectionism scores significantly and uniquely predicted relationship continuity 3 months later. Lastly, controlling for social desirability, relationship commitment status, and Time 1 adult attachment orientation scores, Time 1 dyadic perfectionism scores also uniquely predicted Time 2 relationship distress. Findings provide additional evidence that dyadic perfectionism is a risk factor for relationship dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Towards a Dual-Tip STM Application in Mesoscopic Electron Transport

A new design for a dual-tip scanning tunneling microscope (STM) is presented. The design is a variation on the mechanically controllable break-junction with two electron beam-induced deposition nano-tips. The new design enables one to scan surfaces simultaneously with two probes having a nano-gap separation. By collecting the lateral current flowing between the tips, the transconductance map can then be compared with the STM images for local characterizations of the electron transport. Since the lateral beam carries the property of the density of states of the surface at momentum space, the dispersion of the electronic structure should give an orientation and position dependence of the local transconductance current. In addition, the reduced terminal separation, on the order of the characteristic mesoscopic length scales, is likely to be sensitive to a variety of typically observed interactions and interference effects.     

Almost k-wise independence versus k-wise independence

We say that a distribution over {0,1}ⁿ is (ε,k)-wise independent if its restriction to every k coordinates results in a distribution that is ε-close to the uniform distribution. A natural question regarding (ε,k)-wise independent distributions is how close they are to some k-wise independent distribution. We show that there exist (ε,k)-wise independent distributions whose statistical distance is at least n^O(k)·ε from any k-wise independent distribution. In addition, we show that for any (ε,k)-wise independent distribution there exists some k-wise independent distribution, whose statistical distance is n^O(k)·ε.     

Chalcogenide Glasses Based on Germanium Disulfide for Second Harmonic Generation

High second‐order susceptibilities are created by thermal poling in bulk germanium disulfide based chalcogenide glasses. Experimental conditions of the poling treatment (temperature, voltage, time) were optimized for each glass composition. The second‐order nonlinear signals were recorded by using the Maker fringes experiment and a second‐order coefficient χ⁽²⁾ up to 8 pm V^–1 was measured in the Ge₂₅Sb₁₀S₆₅ glass. This value is obtained using a simulation based on accurate knowledge of the thickness of the nonlinear layer. Two mechanisms are proposed to explain the creation of a nonlinear layer under the anode: the formation and the migration of charged defects towards the anode may mainly occur in Ge₂₀Ga₅Sb₁₀S₆₅ and Ge₂₅Ga₅S₇₀ glasses, whereas the migration of Na⁺ ions towards the cathode may be responsible for the accumulation of negative charges under the anode in Ge₃₃S₆₇ and Ge₂₅Sb₁₀S₆₅ glasses. Different electronic conductivity behaviors seem to be at the origin of the phenomenon. In parallel, the potential effect of the poling treatment on the structural and electronic properties is studied using Raman spectroscopy and secondary ion mass spectroscopy measurements.     

Repeated Budgeted Second Price Ad Auction

Our main goal is to abstract existing repeated sponsored search ad auction mechanisms which incorporate budgets, and study their equilibrium and dynamics. Our abstraction has multiple agents bidding repeatedly for multiple identical items (such as impressions in an ad auction). The agents are budget limited and have a value per item. We abstract this repeated interaction as a one-shot game, which we call budget auction, where agents submit a bid and a budget, and then items are sold by a sequential second price auction. Once an agent exhausts its budget it does not participate in the proceeding auctions. Our main result shows that if agents bid conservatively (never bid above their value) then there always exists a pure Nash equilibrium. We also study simple dynamics of repeated budget auctions, showing their convergence to a Nash equilibrium for two agents and for multiple agents with identical budgets.     

Molecular recognition in the sphingosine 1-phosphate receptor family

Computational modeling and its application in ligand screening and ligand receptor interaction studies play important roles in structure-based drug design. A series of sphingosine 1-phosphate (S1P) receptor ligands with varying potencies and receptor selectivities were docked into homology models of the S1P(1-5) receptors. These studies provided molecular insights into pharmacological trends both across the receptor family as well as at single receptors. This study identifies ligand recognition features that generalize across the S1P receptor family, features unique to the S1P(4) and S1P(5) receptors, and suggests significant structural differences of the S1P(2) receptor. Docking results reveal a previously unknown sulfur-aromatic interaction between the S1P(4) C5.44 sulfur atom and the phenyl ring of benzimidazole as well as pi-pi interaction between F3.33 of S1P(1,4,5) and aromatic ligands. The findings not only confirm the importance of a cation-pi interaction between W4.64 and the ammonium of S1P at S1P(4) but also predict the same interaction at S1P(5). S1P receptor models are validated for pharmacophore development including database mining and new ligand discovery and serve as tools for ligand optimization to improve potency and selectivity.     

Intergranular films at Au-sapphire interfaces

The existence of nanometer-thick amorphous equilibrium films at metal-ceramic interfaces has been experimentally verified for the Au–Al₂O₃ system. The films were formed using a novel experimental approach, in which thin sputtered films of Au were dewetted on a sapphire substrate which was previously partially wetted with drops of anorthite glass (CaO–2SiO₂–Al₂O₃). High-resolution transmission electron microscopy and qualitative analytical transmission electron microscopy were used to confirm the existence of the amorphous films. In addition, positive and relatively large Hamaker constants were calculated for the Au-film-Al₂O₃ interface, which indicates the existence of an attractive van der Waals force which stabilizes the film, similar to equilibrium films at grain boundaries in ceramics. A ∼ 1 nm thick surface film was also detected on the (0001) surface of sapphire substrates partially wetted by anorthite glass. The refractive index required to stabilize the surface films, via a positive Hamaker constant, is explored.