Remote Toehold: A Mechanism for Flexible Control of DNA Hybridization Kinetics

Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes

885-nm Pumped Ceramic Nd:YAG Master Oscillator Power Amplifier Laser System

The performance of a traditional diode pumped solid-state laser that is typically pumped with 808-nm laser diode array (LDA) and crystalline Nd:YAG was improved by using 885-nm LDAs and ceramic Nd:YAG. The advantage is lower quantum defect, which will improve the thermal loading on laser gain medium, resulting in a higher-performance laser. The use of ceramic Nd:YAG allows a higher Nd dopant level that will make up the lower absorption at the 885-nm wavelength on Nd:YAG. When compared to traditional 808-nm pump, 885-nm diodes will have 30% less thermal load (or wasted heat) and will thus see a similar percentage improvement in the overall laser efficiency. In order to provide a more efficient laser system for future flight missions that require the use of low-repetition- rate (1% Nd. To make certain that the absorption at 885 nm is on the same par as the 808-nm diode, the Nd:YAG material needs to be doped with higher concentration of Nd. Ceramic Nd:YAG is the only material that can be tailored to specific needs

Provenance Threat Modeling

Provenance systems are used to capture history metadata, applications include ownership attribution and determining the quality of a particular data set. Provenance systems are also used for debugging, process improvement, understanding data proof of ownership, certification of validity, etc. The provenance of data includes information about the processes and source data that leads to the current representation. In this paper we study the security risks provenance systems might be exposed to and recommend security solutions to better protect the provenance information.Comment: 4 pages, 1 figure, conferenc

Boundary two-parameter eight-state supersymmetric fermion model and Bethe ansatz solution

The recently introduced two-parameter eight-state $U_q[gl(3|1)]$ supersymmetric fermion model is extended to include boundary terms. Nine classes of boundary conditions are constructed, all of which are shown to be integrable via the graded boundary quantum inverse scattering method. The boundary systems are solved by using the coordinate Bethe ansatz and the Bethe ansatz equations are given for all nine cases.Comment: 11 pages, RevTex; some typos correcte

Relationships between student satisfaction and assessment grades in a first-year engineering unit

Monitoring the quality of teaching and learning by universities relies primarily upon a combination of feedback from formal student-evaluation surveys and the long-established measure of student-cohort performance in unit assessments. This study explores major factors that might affect the data provided by these two measures and seeks to identify potential relationships between assessment performance and each of student satisfaction and students’ engineering discipline interests. Enabling this study is a large data-set obtained over the last four years from the teaching of a first-year Engineering Mechanics unit delivered twice per year to approximately 350 students in each semester from all engineering and some of multi-science disciplines. Over these years, this unit has largely remained stable in terms of unit learning outcomes, syllabus, delivery methods and teaching staff, thereby permitting potentially robust conclusions to be drawn from analyses of the data-set. By interrogating this data-set, three questions are addressed in this paper, namely (i) Is there a correlation between academic performance and student satisfaction with the unit, (ii) Did a change in assessment weighting affect students’ overall performance, and (iii) Does student interest, as reflected by their engineering-oriented discipline choice, affect their overall assessment outcomes. The investigations presented in this paper are preliminary, focusing on four-semester studies in 2010 and 2011, adopting a broad-brush approach, in order to provide the direction to more refined and rigorous lines of enquiry using the same data to determine the efficacy of present monitoring systems for teaching and learning.The initial results show that student feedback is correlated well to their assessment performance provided that cultural bias is removed. Overall, the influence on performance of changing the assessment weighting appears to be minimal and does the students’ engineering-discipline interests

Space-Based Lasers for Remote Sensing Applications

There are currently three operational lidar systems orbiting the Earth, the Moon and the planet Mercury gathering scientific data and images to form a better understanding of our Earth and solar system. In this paper we will present an overview of the spacebome laser programs and offer insights into future spacebome lasers for remote sensing applications

Control the host cell cycle: Viral regulation of the anaphase-promoting complex

Viruses commonly manipulate cell cycle progression to create cellular conditions that are most beneficial to their replication. To accomplish this feat, viruses often target critical cell cycle regulators in order to have maximal effect with minimal input. One such master regulator is the large, multisubunit E3 ubiquitin ligase anaphase-promoting complex (APC) that targets effector proteins for ubiquitination and proteasome degradation. The APC is essential for cells to progress through anaphase, exit from mitosis, and prevent a premature entry into S phase. These far-reaching effects of the APC on the cell cycle are through its ability to target a number of substrates, including securin, cyclin A, cyclin B, thymidine kinase, geminin, and many others. Recent studies have identified several proteins from a number of viruses that can modulate APC activity by different mechanisms, highlighting the potential of the APC in driving viral replication or pathogenesis. Most notably, human cytomegalovirus (HCMV) protein pUL21a was recently identified to disable the APC via a novel mechanism by targeting APC subunits for degradation, both during virus infection and in isolation. Importantly, HCMV lacking both viral APC regulators is significantly attenuated, demonstrating the impact of the APC on a virus infection. Work in this field will likely lead to novel insights into viral replication and pathogenesis and APC function and identify novel antiviral and anticancer targets. Here we review viral mechanisms to regulate the APC, speculate on their roles during infection, and identify questions to be addressed in future studies

De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function.

The splicing regulator Polypyrimidine Tract Binding Protein (PTBP1) has four RNA binding domains that each binds a short pyrimidine element, allowing recognition of diverse pyrimidine-rich sequences. This variation makes it difficult to evaluate PTBP1 binding to particular sites based on sequence alone and thus to identify target RNAs. Conversely, transcriptome-wide binding assays such as CLIP identify many in vivo targets, but do not provide a quantitative assessment of binding and are informative only for the cells where the analysis is performed. A general method of predicting PTBP1 binding and possible targets in any cell type is needed. We developed computational models that predict the binding and splicing targets of PTBP1. A Hidden Markov Model (HMM), trained on CLIP-seq data, was used to score probable PTBP1 binding sites. Scores from this model are highly correlated (ρ = -0.9) with experimentally determined dissociation constants. Notably, we find that the protein is not strictly pyrimidine specific, as interspersed Guanosine residues are well tolerated within PTBP1 binding sites. This model identifies many previously unrecognized PTBP1 binding sites, and can score PTBP1 binding across the transcriptome in the absence of CLIP data. Using this model to examine the placement of PTBP1 binding sites in controlling splicing, we trained a multinomial logistic model on sets of PTBP1 regulated and unregulated exons. Applying this model to rank exons across the mouse transcriptome identifies known PTBP1 targets and many new exons that were confirmed as PTBP1-repressed by RT-PCR and RNA-seq after PTBP1 depletion. We find that PTBP1 dependent exons are diverse in structure and do not all fit previous descriptions of the placement of PTBP1 binding sites. Our study uncovers new features of RNA recognition and splicing regulation by PTBP1. This approach can be applied to other multi-RRM domain proteins to assess binding site degeneracy and multifactorial splicing regulation