The telomerase essential N-terminal domain promotes DNA synthesis by stabilizing short RNA-DNA hybrids.

Telomerase is an enzyme that adds repetitive DNA sequences to the ends of chromosomes and consists of two main subunits: the telomerase reverse transcriptase (TERT) protein and an associated telomerase RNA (TER). The telomerase essential N-terminal (TEN) domain is a conserved region of TERT proposed to mediate DNA substrate interactions. Here, we have employed single molecule telomerase binding assays to investigate the function of the TEN domain. Our results reveal telomeric DNA substrates bound to telomerase exhibit a dynamic equilibrium between two states: a docked conformation and an alternative conformation. The relative stabilities of the docked and alternative states correlate with the number of basepairs that can be formed between the DNA substrate and the RNA template, with more basepairing favoring the docked state. The docked state is further buttressed by the TEN domain and mutations within the TEN domain substantially alter the DNA substrate structural equilibrium. We propose a model in which the TEN domain stabilizes short RNA-DNA duplexes in the active site of the enzyme, promoting the docked state to augment telomerase processivity

Teaching Compositionality to CNNs

Convolutional neural networks (CNNs) have shown great success in computer vision, approaching human-level performance when trained for specific tasks via application-specific loss functions. In this paper, we propose a method for augmenting and training CNNs so that their learned features are compositional. It encourages networks to form representations that disentangle objects from their surroundings and from each other, thereby promoting better generalization. Our method is agnostic to the specific details of the underlying CNN to which it is applied and can in principle be used with any CNN. As we show in our experiments, the learned representations lead to feature activations that are more localized and improve performance over non-compositional baselines in object recognition tasks.Comment: Preprint appearing in CVPR 201

Wave Equation for Sound in Fluids with Vorticity

We use Clebsch potentials and an action principle to derive a closed system of gauge invariant equations for sound superposed on a general background flow. Our system reduces to the Unruh (1981) and Pierce (1990) wave equations when the flow is irrotational, or slowly varying. We illustrate our formalism by applying it to waves propagating in a uniformly rotating fluid where the sound modes hybridize with inertial waves.Comment: RevTeX, 27page

Bohr-Sommerfeld quantization of spin Hamiltonians

The Bohr-Sommerfeld rule for a spin system is obtained, including the first quantum corrections. The rule applies to both integer and half-integer spin, and respects Kramers degeneracy for time-reversal invariant systems. It is tested for various models, in particular the Lipkin-Meshkov-Glick model, and found to agree very well with exact results.Comment: Revtex 4, no figures, 1 tabl

Quantifying the effect of interannual ocean variability on the attribution of extreme climate events to human influence

In recent years, the climate change research community has become highly interested in describing the anthropogenic influence on extreme weather events, commonly termed "event attribution." Limitations in the observational record and in computational resources motivate the use of uncoupled, atmosphere/land-only climate models with prescribed ocean conditions run over a short period, leading up to and including an event of interest. In this approach, large ensembles of high-resolution simulations can be generated under factual observed conditions and counterfactual conditions that might have been observed in the absence of human interference; these can be used to estimate the change in probability of the given event due to anthropogenic influence. However, using a prescribed ocean state ignores the possibility that estimates of attributable risk might be a function of the ocean state. Thus, the uncertainty in attributable risk is likely underestimated, implying an over-confidence in anthropogenic influence. In this work, we estimate the year-to-year variability in calculations of the anthropogenic contribution to extreme weather based on large ensembles of atmospheric model simulations. Our results both quantify the magnitude of year-to-year variability and categorize the degree to which conclusions of attributable risk are qualitatively affected. The methodology is illustrated by exploring extreme temperature and precipitation events for the northwest coast of South America and northern-central Siberia; we also provides results for regions around the globe. While it remains preferable to perform a full multi-year analysis, the results presented here can serve as an indication of where and when attribution researchers should be concerned about the use of atmosphere-only simulations

Structural basis of template-boundary definition in Tetrahymena telomerase.

Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides

Fusion products, Kostka polynomials, and fermionic characters of su(r+1)_k

Using a form factor approach, we define and compute the character of the fusion product of rectangular representations of \hat{su}(r+1). This character decomposes into a sum of characters of irreducible representations, but with q-dependent coefficients. We identify these coefficients as (generalized) Kostka polynomials. Using this result, we obtain a formula for the characters of arbitrary integrable highest-weight representations of \hat{su}(r+1) in terms of the fermionic characters of the rectangular highest weight representations.Comment: 21 pages; minor changes, typos correcte

The Gradient Expansion for the Free-Energy of a Clean Superconductor

We describe a novel method for obtaining the gradient expansion for the free energy of a clean BCS superconductor. We present explicit results up to fourth order in the gradients of the order parameter.Comment: 33 pages, Late

Hydrodynamical simulations of the decay of high-speed molecular turbulence. I. Dense molecular regions

We present the results from three dimensional hydrodynamical simulations of decaying high-speed turbulence in dense molecular clouds. We compare our results, which include a detailed cooling function, molecular hydrogen chemistry and a limited C and O chemistry, to those previously obtained for decaying isothermal turbulence. After an initial phase of shock formation, power-law decay regimes are uncovered, as in the isothermal case. We find that the turbulence decays faster than in the isothermal case because the average Mach number remains higher, due to the radiative cooling. The total thermal energy, initially raised by the introduction of turbulence, decays only a little slower than the kinetic energy. We discover that molecule reformation, as the fast turbulence decays, is several times faster than that predicted for a non-turbulent medium. This is caused by moderate speed shocks which sweep through a large fraction of the volume, compressing the gas and dust. Through reformation, the molecular density and molecular column appear as complex patterns of filaments, clumps and some diffuse structure. In contrast, the molecular fraction has a wider distribution of highly distorted clumps and copious diffuse structure, so that density and molecular density are almost identically distributed during the reformation phase. We conclude that molecules form in swept-up clumps but effectively mix throughout via subsequent expansions and compressions.Comment: 12 pages, 12 figures; For a version of the article with higher resolution figures, see http://star.arm.ac.uk/preprints/381.p

End states, ladder compounds, and domain wall fermions

A magnetic field applied to a cross linked ladder compound can generate isolated electronic states bound to the ends of the chain. After exploring the interference phenomena responsible, I discuss a connection to the domain wall approach to chiral fermions in lattice gauge theory. The robust nature of the states under small variations of the bond strengths is tied to chiral symmetry and the multiplicative renormalization of fermion masses.Comment: 10 pages, 4 figures; final version for Phys. Rev. Let