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

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

Construction and Interim Performance of a Pyrament Cement Concrete Bridge Deck

Pyrament Blended Cement (PBC) is a high performance cement developed by Lone Star Industries and is a blend of 65% portland cement, 30% fly ash, and 5% trademark additive. Concrete made with PBC has been characterized by its rapid set, high early strength, and low permeability. This report summarizes the construction and interim performance of a full-depth concrete bridge deck slab constructed using Pyrament Cement concrete

Performance of Pyrament Cement Concrete in a Highway Bridge Deck

Pyrament Blended Cement (PBC) is a high performance cement that was developed by Lone Star Industries. Concrete that is made with PBC is rapid setting, has high strength and low permeability. The Kentucky Transportation Cabinet chose to use PBC concrete in a lull·depth bridge deck. The objectives of this study were to evaluate the construction and performance of a full-depth bridge deck constructed of PBC concrete and to compare the data obtained to historical construction and performance properties of conventional, Class AA bridge deck concrete. This report provides information relative to construction activities, materials properties, and a summary of the three-year performance of the experimental bridge deck

Construction and Interim Performance of a Shrinkage Compensating (Class S) Bridge Deck Concrete

Shrinkage Compensating Concrete (Class S) is made with an expansive cement in which the expansion, if restrained, induces compressive stresses that approximately offset tensile stresses induced during drying shrinkage, thereby eliminating or significantly reducing the occurrence of shrinkage cracking in concrete. The objectives of this study were to evaluate the construction and performance of the Shrinkage Compensating Concrete (Class S) and to compare these characteristics to previous Class S concrete data and to conventional Class AA bridge deck concrete. This report summarizes the construction activities and interim performance of experimental decks and barrier walls constructed of shrinkage compensating concrete

Performance of Shrinkage Compensating Bridge Deck Concrete (Class S) I-75, Kenton County

Shrinkage Compensating Concrete (Class S) is made with an expansive cement in which the expansion, if restrained, induces compressive stresses that approximately offset tensile stresses induced during drying shrinkage, thereby eliminating or significantly reducing the occurrence of shrinkage cracking in concrete. The objectives of this study were to evaluate the construction and performance of the Shrinkage Compensating Concrete (Class S) and to compare these characteristics to previous Class S concrete data and to conventional Class AA bridge deck concrete. This report summarizes construction activities and provides final performance evaluations and recommendations relative to experimental decks and barrier walls constructed of shrinkage compensating concrete during the widening and reconstruction of 1·75 in Kenton County, Kentucky

Use of Class AA Concrete Modified with a High-Range Water Reducing Admixture in a Full-Depth Bridge Deck Slab US 127, Lincoln County

Because it is desirable for bridge deck concrete to be strong and durable, the Kentucky Department of Highways chose to use a high-range water reducer to modify the properties of a conventional Class AA concrete mixture to be placed in a full-depth concrete bridge deck on US 127 in Lincoln County. A high-range water reducer is a chemical admixture that when added to low-to-normal slump concrete produces a high slump to flowing concrete. The higher slump enhances placement properties in areas of closely spaced and congested reinforcing steel such as that encountered in the corners of a skewed bridge structure. The addition of a high-range water reducer permits reductions in mix water in the range of 12 to 30 percent. The reduction in mix water lowers the water-to-cement ratio leading to increased strength properties. The Kentucky Department of Highways specified an admixture dosage rate of 10.42 mL per kilogram of cement (16.0 oz per 100 lbs of cement). Test results indicated that this dosage rate would facilitate the desired 15 percent reduction in the available mix water. The use of a high-slump concrete enhances placement properties in areas of closely spaced reinforcing steel such as a skewed bridge structure. Data obtained during this study indicate that the high-range water reducing admixture also enhances durability and strength properties of concrete. The magnitude of cracking was slightly more for the experimental deck concrete but the severity of the cracks appeared to be higher in the control deck. The inability to adhere to the specified admixture rate compounded by the finishing characteristics of the concrete mixture contributed to the poor results achieved with the experimental deck. The admixture representative present during the experimental deck placement could not provide the suitable proportioning of the admixtures necessary for both a good finishing mix that also met the requirements of the project. It is recommended that consideration be given again to the use of high-range water reducers to modify conventional bridge deck concrete in situations where the placement properties can be enhanced or where it is desired to enhance strength and durability properties. The positive attributes of the modified concrete identified in this project make it worthwhile to gain additional experience with the use of these admixtures. It is recommended the specifications be revised for any future projects to require that trial batches be performed until two separate batches conform to all specification requirements and that the bridge contractor have his intended placement and finishing personnel at the trial placements to gain experience