Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair

Studies in knockout mice provide evidence that MSH2–MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2–MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis, and bypasses them on the template strand to cause deletion. Remarkably, MSH2–MSH3 not only stimulates pol β to copy through the repeats but also enhances formation of the flap precursor for expansion. Our results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway that changes the outcome of TNR instability from deletion to expansion during the removal of oxidized bases. We propose that cells implement crosstalk strategies and share machinery when a canonical pathway is ineffective in removing a difficult lesion

Renormalization Group and Decoupling in Curved Space: II. The Standard Model and Beyond

We continue the study of the renormalization group and decoupling of massive fields in curved space, started in the previous article and analyse the higher derivative sector of the vacuum metric-dependent action of the Standard Model. The QCD sector at low-energies is described in terms of the composite effective fields. For fermions and scalars the massless limit shows perfect correspondence with the conformal anomaly, but similar limit in a massive vector case requires an extra compensating scalar. In all three cases the decoupling goes smoothly and monotonic. A particularly interesting case is the renormalization group flow in the theory with broken supersymmetry, where the sign of one of the beta-functions changes on the way from the UV to IR.Comment: 27 pages, 8 figure

Tuning into the real effect of smartphone use on parenting: A multiverse analysis

Background Concerns have been raised regarding the potential negative impacts of parents' smartphone use on the parent-child relationship. A scoping literature review indicated inconsistent effects, arguably attributable to different conceptualizations of parent phone use and conflation of phone use with technological interference. Methods Based on a sample of n = 3, 659 parents collected in partnership with a national public broadcaster, we conducted a multiverse analysis. We explored 84 different analytic choices to address whether associations were weak versus robust, and provide clearer direction for measurement, theory, and practice. Effects were assessed in relation to p values, effect sizes, and AIC; we further conducted a meta‐analytic sensitivity check. Results Direct associations between smartphone use and parenting were relatively weak and mixed. Instead, the relation between use and parenting depended on level of technological interference. This pattern was particularly robust for family displacement. At low levels of displacing time with family using technology, more smartphone use was associated with better (not worse) parenting. Conclusions Our results indicate fragility in findings of risks for parental smartphone use on parenting; there were few concerns in this regard. Rather, at low levels of technological interference, more phone use was associated with higher parenting quality. Scholars should avoid generalized narratives of family risk and seek to uncover real effects of smartphone use on family outcomes across diverse households and contexts

The 1:1 resonance in Extrasolar Systems: Migration from planetary to satellite orbits

We present families of symmetric and asymmetric periodic orbits at the 1/1 resonance, for a planetary system consisting of a star and two small bodies, in comparison to the star, moving in the same plane under their mutual gravitational attraction. The stable 1/1 resonant periodic orbits belong to a family which has a planetary branch, with the two planets moving in nearly Keplerian orbits with non zero eccentricities and a satellite branch, where the gravitational interaction between the two planets dominates the attraction from the star and the two planets form a close binary which revolves around the star. The stability regions around periodic orbits along the family are studied. Next, we study the dynamical evolution in time of a planetary system with two planets which is initially trapped in a stable 1/1 resonant periodic motion, when a drag force is included in the system. We prove that if we start with a 1/1 resonant planetary system with large eccentricities, the system migrates, due to the drag force, {\it along the family of periodic orbits} and is finally trapped in a satellite orbit. This, in principle, provides a mechanism for the generation of a satellite system: we start with a planetary system and the final stage is a system where the two small bodies form a close binary whose center of mass revolves around the star.Comment: to appear in Cel.Mech.Dyn.Ast

Influence of consecutive sediment replenishment on channel bed morphology

Dams interrupt the longitudinal connectivity of a river as they store water and trap sediment. When transport capacity downstream of dams exceeds sediment supply, water becomes hungry and channel incision, bed armouring and reduction of morphological diversity are the consequences. Sediment replenishment is an increasingly common measure to restore the sediment regime of such disturbed river reaches. In the present study the influence on channel bed morphology of different geometrical configuration of replenishments and of consecutive gravel augmentation is assessed by means of systematically laboratory experiments. The typical features of a straight armoured alpine gravel channel are reproduced on the model in terms of slope, cross section and bed grain size. The total amount of replenished sediment is deposited in four identical volumes following two different geometrical configurations (parallel and alternating). The reaction of the channel bed is analysed on image and laser data. Persistency of the first replenishment is high and it covers a large portion of the channel bed, which consequently decreases channel bed roughness remarkably. The persistency of the second replenishment is low and the effect on the depositional pattern established after the first replenishment only minor. This is explained by the smoothing of the channel bed during the first replenishment, resulting in higher transport capacities. For the alternating configuration an increase in the deposition heights in the very downstream channel reach can be observed due to the second replenishment. Thus it is assumed that consecutive replenishment can increase the impact length of restoration projects. The parallel configuration results in very spread depositions, while for the alternating configuration a clear bed form pattern could be observed with a wavelength of depositions corresponding to the length of the replenished volumes. These depositions are understood as mounds, forming the initial condition of alternating bars. Thus in order to enhance channel bed topography of an armoured layer downstream a dam, sediment replenishment added by the alternating configuration is most favourable and effective

Enhancement of Rabi Splitting in a Microcavity with an Embedded Superlattice

We have observed a large coupling between the excitonic and photonic modes of an AlAs/AlGaAs microcavity filled with an 84-({\rm {\AA}})/20({\rm {\AA}}) GaAs/AlGaAs superlattice. Reflectivity measurements on the coupled cavity-superlattice system in the presence of a moderate electric field yielded a Rabi splitting of 9.5 meV at T = 238 K. This splitting is almost 50% larger than that found in comparable microcavities with quantum wells placed at the antinodes only. We explain the enhancement by the larger density of optical absorbers in the superlattice, combined with the quasi-two-dimensional binding energy of field-localized excitons.Comment: 5 pages, 4 figures, submitted to PR

Critical points in edge tunneling between generic FQH states

A general description of weak and strong tunneling fixed points is developed in the chiral-Luttinger-liquid model of quantum Hall edge states. Tunneling fixed points are a subset of `termination' fixed points, which describe boundary conditions on a multicomponent edge. The requirement of unitary time evolution at the boundary gives a nontrivial consistency condition for possible low-energy boundary conditions. The effect of interactions and random hopping on fixed points is studied through a perturbative RG approach which generalizes the Giamarchi-Schulz RG for disordered Luttinger liquids to broken left-right symmetry and multiple modes. The allowed termination points of a multicomponent edge are classified by a B-matrix with rational matrix elements. We apply our approach to a number of examples, such as tunneling between a quantum Hall edge and a superconductor and tunneling between two quantum Hall edges in the presence of interactions. Interactions are shown to induce a continuous renormalization of effective tunneling charge for the integrable case of tunneling between two Laughlin states. The correlation functions of electronlike operators across a junction are found from the B matrix using a simple image-charge description, along with the induced lattice of boundary operators. Many of the results obtained are also relevant to ordinary Luttinger liquids.Comment: 23 pages, 6 figures. Xiao-Gang Wen: http://dao.mit.edu/~we

Interface electronic states and boundary conditions for envelope functions

The envelope-function method with generalized boundary conditions is applied to the description of localized and resonant interface states. A complete set of phenomenological conditions which restrict the form of connection rules for envelope functions is derived using the Hermiticity and symmetry requirements. Empirical coefficients in the connection rules play role of material parameters which characterize an internal structure of every particular heterointerface. As an illustration we present the derivation of the most general connection rules for the one-band effective mass and 4-band Kane models. The conditions for the existence of Tamm-like localized interface states are established. It is shown that a nontrivial form of the connection rules can also result in the formation of resonant states. The most transparent manifestation of such states is the resonant tunneling through a single-barrier heterostructure.Comment: RevTeX4, 11 pages, 5 eps figures, submitted to Phys.Rev.

Skewed X-chromosome inactivation in scleroderma

Scleroderma is a female-prevalent autoimmune disease of unclear etiology. Two fundamental gender differences, skewed X-chromosome inactivation (XCI) and pregnancy-related microchimerism, have been implicated in scleroderma. We investigated the XCI patterns of female scleroderma patients and the parental origin of the inactive X chromosome in those patients having skewed XCI patterns (>80%). In addition, we investigated whether a correlation exists between XCI patterns and microchimerism in a well-characterized cohort. About 195 female scleroderma patients and 160 female controls were analyzed for the androgen receptor locus to assess XCI patterns in the DNA extracted from peripheral blood cells. Skewed XCI was observed in 67 (44.9%) of 149 informative patients and in 10 of 124 healthy controls (8.0%) [odds ratio (OR) = 9.3 (95% confidence interval (CI) 4.3-20.6, P 90%) was present in 44 of 149 patients (29.5%) but only in 3 of 124 controls (2.4%; OR = 16.9; 95% CI 4.8-70.4, P < 0.0001). Parental origin of the inactive X chromosome was investigated for ten patients for whom maternal DNA was informative, and the inactive X chromosome was of maternal origin in eight patients and of paternal origin in two patients. Skewed XCI mosaicism could be considered as an important risk factor in scleroderma. © 2007 Humana Press Inc