Matching Items (4)

A self-regulating template in human telomerase

Description

Telomerase is a specialized reverse transcriptase (RT) containing an intrinsic telomerase RNA (TR) component. It synthesizes telomeric DNA repeats, (GGTTAG)n in humans, by reiteratively copying a precisely defined, short template

Telomerase is a specialized reverse transcriptase (RT) containing an intrinsic telomerase RNA (TR) component. It synthesizes telomeric DNA repeats, (GGTTAG)n in humans, by reiteratively copying a precisely defined, short template sequence from the integral TR. The specific mechanism of how the telomerase active site uses this short template region accurately and efficiently during processive DNA repeat synthesis has remained elusive. Here we report that the human TR template, in addition to specifying the DNA sequence, is embedded with a single-nucleotide signal to pause DNA synthesis. After the addition of a dT residue to the DNA primer, which is specified by the 49 rA residue in the template, telomerase extends the DNA primer with three additional nucleotides and then pauses DNA synthesis. This sequence-defined pause site coincides precisely with the helix paired region 1 (P1)-defined physical template boundary and precludes the incorporation of nontelomeric nucleotides from residues outside the template region. Furthermore, this sequence-defined pausing mechanism is a key determinant, in addition to the P1-defined template boundary, for generating the characteristic 6-nt ladder banding pattern of telomeric DNA products in vitro. In the absence of the pausing signal, telomerase stalls nucleotide addition at multiple sites along the template, generating DNA products with heterogeneous terminal repeat registers. Our findings demonstrate that this unique self-regulating mechanism of the human TR template is essential for high-fidelity synthesis of DNA repeats.

Contributors

Agent

Created

Date Created
  • 2014-08-05

153690-Thumbnail Image.png

Three dimensional characterization of microstructural effects on spall damage in shocked polycrystalline copper

Description

Shock loading is a complex phenomenon that can lead to failure mechanisms such as strain localization, void nucleation and growth, and eventually spall fracture. The length scale of damage with

Shock loading is a complex phenomenon that can lead to failure mechanisms such as strain localization, void nucleation and growth, and eventually spall fracture. The length scale of damage with respect to that of the surrounding microstructure has proven to be a key aspect in determining sites of failure initiation. Studying incipient stages of spall damage is of paramount importance to accurately determine initiation sites in the material microstructure where damage will nucleate and grow and to formulate continuum models that account for the variability of the damage process due to microstructural heterogeneity, which is the focus of this research. Shock loading experiments were conducted via flyer-plate impact tests for pressures of 2-6 GPa and strain rates of 105/s on copper polycrystals of varying thermomechanical processing conditions. Serial cross sectioning of recovered target disks was performed along with electron microscopy, electron backscattering diffraction (EBSD), focused ion beam (FIB) milling, and 3-D X-ray tomogrpahy (XRT) to gain 2-D and 3-D information on the spall plane and surrounding microstructure. Statistics on grain boundaries (GB) containing damage were obtained from 2-D data and GBs of misorientations 25° and 50° were found to have the highest probability to contain damage in as-received (AR), heat treated (HT), and fully recrystallized (FR) microstructures, while {111} Σ3 GBs were globally strong. The AR microstructure’s probability peak was the most pronounced indicating GB strength is the dominant factor for damage nucleation. 3-D XRT data was used to digitally render the spall planes of the AR, HT, and FR microstructures. From shape fitting the voids to ellipsoids, it was found that the AR microstructure contained greater than 55% intergranular damage, whereas the HT and FR microstructures contained predominantly transgranular and coalesced damage modes, respectively. 3-D reconstructions of large volume damage sites in shocked Cu multicrystals showed preference for damage nucleation at GBs between adjacent grains of a high Taylor factor mismatches as well as an angle between the shock direction and the GB physical normal of ~30°-45°. 3-D FIB sectioning of individual voids led to the discovery of uniform plastic zones ~25-50% the size of the void diameter and plastic deformation directions were characterized via local average misorientation maps. Incipient transgranular voids revealed from the sectioning process were present in grains of high Taylor factors along the shock direction, which is expected as materials with a low Taylor factor along the shock direction are susceptible to growth due their accomodation of plastic deformation. Fabrication of square waves using photolithography and chemical etching was developed to study the nature of plasticity at GBs away from the spall plane. Grains oriented close to <0 1 1> had half the residual amplitudes than grains oriented close to <0 0 1>.

Contributors

Agent

Created

Date Created
  • 2015

155101-Thumbnail Image.png

Measuring the effectiveness of enterprise application training: a comparative analysis of dynamic and integrated instruction

Description

The purpose of this study was to investigate the impacts of three types of instructional presentation methods on learning, efficiency, cognitive load, and learner attitude. A total of 67

The purpose of this study was to investigate the impacts of three types of instructional presentation methods on learning, efficiency, cognitive load, and learner attitude. A total of 67 employees of a large southwestern university working in the field of research administration were randomly assigned to one of three conditions. Each condition presented instructional materials using a different method, namely dynamic integrated, dynamic non-integrated, or non-dynamic non-integrated. Participants completed a short survey, pre-test, cognitive load questions, learner attitude questions, and a post-test during their experience. The results reveal that users of the dynamic integrated condition treatment showed significant improvement in both learning and efficiency. The dynamic non-integrated participants had a faster mean time to complete an assigned task, however, they also had significantly lower average test scores. There were no other significant findings in terms of cognitive load or learner attitude. Limitations, implications and future studies are discussed.

Contributors

Agent

Created

Date Created
  • 2016

153646-Thumbnail Image.png

Utopia as heresy: hope, possibility, and the cultural imaginary

Description

The utopian impulse represents hope for another world; a reflection of the injustices inherent to the hegemonic order that are understood as natural, necessary, desirable, and unchangeable. Those who challenge

The utopian impulse represents hope for another world; a reflection of the injustices inherent to the hegemonic order that are understood as natural, necessary, desirable, and unchangeable. Those who challenge this orthodoxy are heretical utopians; pioneers of the counterintuitive who explore the types of relations that rather than reproduce the dominant order, shatter it, and manifest new ones based upon principles of justice. This project explores how ideological mechanisms of control embedded within the hegemonic fascist imaginary landscape of the United States render the visions of emancipatory social movements, that challenge dominant ways of knowing and being, as the "merely utopian" so as to instrumentalize the behavior of civil-society towards the maintenance of the established social order and the suppression of alternatives (Gordon 2004). In a rapidly changing world reeling under the pressures of late-stage capitalism, it is essential for those who value social and political justice to incessantly cultivate the cultural imaginary so as to shift the boundaries of what types of social relations are possible, feasible, and desirable through the process of struggle in heretical spaces.

Contributors

Agent

Created

Date Created
  • 2015