Rotordynamic coefficients for labyrinth seals calculated by means of a finite difference technique

The compressible, turbulent, time dependent and three dimensional flow in a labyrinth seal can be described by the Navier-Stokes equations in conjunction with a turbulence model. Additionally, equations for mass and energy conservation and an equation of state are required. To solve these equations, a perturbation analysis is performed yielding zeroth order equations for centric shaft position and first order equations describing the flow field for small motions around the seal center. For numerical solution a finite difference method is applied to the zeroth and first order equations resulting in leakage and dynamic seal coefficients respectively

A plug and play spoken dialogue interface for smart environments

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-540-24630-5_44Proceedings of 5th International Conference, CICLing 2004 Seoul, Korea, February 15-21, 2004In this paper we present a plug and play dialogue system for smart environments. The environment description and its state are stored on a domain ontology. This ontology is formed by entities that represent real world contextual information and abstract concepts. This information is complemented with linguistic parts that allow to automatically create a spoken interface for the environment. The spoken interface is based on multiple dialogues, related to every ontology entity with linguistic information. Firstly, the dialogue system creates appropriate grammars for the dialogues. Secondly, it creates the dialogue parts, employing a tree structure. Grammars support the recognition process and the dialogue tree supports the interpretation and generation processes. The system is being tested with a prototype formed by a living room. Users may interact with and modify the physical state of this living room environment by means of the spoken dialogue interface.This paper has been sponsored by the Spanish Ministry of Science and Technology, project number TIC2000-046

Evaluation of Rotordynamic Coefficients of Look-through Labyrinths by Means of a Three Volume Bulk Flow Model

To describe the compressible, turbulent flow in a labyrinth seal, a three volume bulk flow model is presented. The conservation equations for mass, momentum, and energy are established in every control volume. A perturbation analysis is performed, yielding zeroth order equations for centric rotor position and first order equations describing the flow field for small rotor motions around the seal center. The equations are integrated numerically. From perturbation pressure, the forces on the shaft and the dynamic coefficients are calculated

Replication Protein A (RPA) Targeting of Uracil DNA Glycosylase (UNG2)

Replication Protein A (RPA) is a single stranded DNA binding protein which stabilizes ssDNA for replication and repair. One function of RPA is to bind the DNA repair enzyme uracil DNA glycosylase (UNG2) and direct its activity towards ssDNA dsDNA junctions. UNG2 removes uracil bases from DNA which can appear through dUMP misincorporation or through cytosine deamination. If uracil is present instead of a cytosine, then the original GC pair becomes a GU pair. The uracil will then base pair to adenine in the replicated daughter strand. This results in a GC → AT mutation that could contribute to cancer formation. RPA is known to target UNG2 towards individual uracil bases. We hypothesize that RPA will target UNG2 to uracil bases in DNA regardless of the number of uracils in the DNA strand

Interaction of Fluorescent Probes with Sirtuin Proteins

Sirtuins are a class of proteins belonging to the Sir2 (Silencing information regulator 2) family of NAD+ dependent protein lysine deacylases. Different Isoforms (SIRT1-SIRT7) differ in their specific deacylase activity and cellular location. They have roles in DNA repair, glucose metabolism, and cellular proliferation which make them highly desirable targets for carcinoma therapeutics. We previously used 1-aminoanthracene’s (AMA) fluorescent properties when bound with SIRT2 (Kd of 37 μM) to develop a high-throughput screen to identify novel ligands that inhibit SIRT2’s enzymatic activities. We hope to reveal other potential probes for future high-throughput screening with all the sirtuin isotopes. 1-AMA’s fluorescence along with fluorescent labeled peptides “Cy3-PEG4-H4K16(myr)” and “FAM-PEG4-H4K16(myr)” were used in binding assays to determine their affinities with SIRT2, SIRT3, and SIRT6. Further, we determined 1-AMA’s ability to bind sirtuin isoforms when they were equilibrated with 100 μM of various acyl-peptides. 1-AMA displays weak binding to SIRT3 and SIRT6 when compared to SIRT2. FAM-PEG4-H4K16(myr) binds SIRT2 with a Kd of 7nM which is much higher than its interaction with SIRT3 and SIRT6 (Kd of 6 μM and 2 μM, respectively). Cy3-PEG4-H4K16(myr) binds as expected SIRT2,3,6 although its affinity for SIRT6 changes minimally with the addition of ADP-ribose, which suggests Cy3 may facilitate binding in the absence of SIRT6’s co-factor. Future work will test additional probes with the other sirtuin proteins and establish their competency to be utilized for high-throughput screening

Effect of Uracil DNA Glycosylase Activity on the Efficacy of Thymidylate Synthase Inhibitor/HDAC Inhibitor Combination Therapies in Colon Cancer

Human uracil DNA glycosylase (UNG2) is responsible for removing uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5-fluorouracil, fluorodeoxyuridine, and pemetrexed) and we determined that, except for 5-fluorouracil, all other TS inhibitors were significantly more potent in UNG2 KO cells compared to wild-type HT29 cells. Interestingly, UNG2 protein levels can also be depleted by the HDAC inhibitors SAHA and MS275, providing a pharmacologic strategy to reduce UNG2 activity in cells. Unexpectedly, the HDAC inhibitors synergized with 5-fluorouracil but not fluorodeoxyuridine in both wild-type and UNG2-knockout cells. Similarly, HDAC inhibitors synergized with pemetrexed in wild-type HT29 but not UNG2-knockout cells. This suggested that HDAC inhibitors sensitized cells to 5-fluorouracil through an UNG2-independent mechanism. Interestingly, SAHA depleted the UNG2 level, whereas TS inhibitors alone and their combination with SAHA upregulated the level of UNG2 at 24 hours. This suggests HDAC inhibitors deplete UNG2 but, when combined with TS inhibitors, it did not affect UNG2, at least at a concentration of 100nM. Our future aim is to study these pharmacological drug combinations targeting UNG2 activity in cells and elucidate exact mechanisms of cell death

Development of a National Repository of Digital Forensic Intelligence

Many people do all of their banking online, we and our children communicate with peers through computer systems, and there are many jobs that require near continuous interaction with computer systems. Criminals, however, are also “connected”, and our online interaction provides them a conduit into our information like never before. Our credit card numbers and other fiscal information are at risk, our children\u27s personal information is exposed to the world, and our professional reputations are on the line.The discipline of Digital Forensics in law enforcement agencies around the nation and world has grown to match the increased risk and potential for cyber crimes. Even crimes that are not themselves computer-based, may be solved or prosecuted based on digital evidence left behind by the perpetrator. However, no widely accepted mechanism to facilitate sharing of ideas and methodologies has emerged. Different agencies re-develop approaches that have been tested in other jurisdictions. Even within a single agency, there is often significant redundant work. There is great potential efficiency gain in sharing information from digital forensic investigations.This paper describes an on-going design and development project between Oklahoma State University’s Center for Telecommunications and Network Security and the Defense Cyber Crimes Center to develop a Repository of Digital Forensic Knowledge. In its full implementation, the system has potential to provide exceptional gains in efficiency for examiners and investigators. It provides a better conduit to share relevant information between agencies and a structure through which cases can be cross-referenced to have the most impact on a current investigation

Development of A National Repository of Digital Forensic Intelligence

Many people do all of their banking online, we and our children communicate with peers through computer systems, and there are many jobs that require near continuous interaction with computer systems. Criminals, however, are also “connected”, and our online interaction provides them a conduit into our information like never before. Our credit card numbers and other fiscal information are at risk, our children\u27s personal information is exposed to the world, and our professional reputations are on the line. The discipline of Digital Forensics in law enforcement agencies around the nation and world has grown to match the increased risk and potential for cyber crimes. Even crimes that are not themselves computer-based, may be solved or prosecuted based on digital evidence left behind by the perpetrator. However, no widely accepted mechanism to facilitate sharing of ideas and methodologies has emerged. Different agencies re-develop approaches that have been tested in other jurisdictions. Even within a single agency, there is often significant redundant work. There is great potential efficiency gain in sharing information from digital forensic investigations. This paper describes an on-going design and development project between Oklahoma State University’s Center for Telecommunications and Network Security and the Defense Cyber Crimes Center to develop a Repository of Digital Forensic Knowledge. In its full implementation, the system has potential to provide exceptional gains in efficiency for examiners and investigators. It provides a better conduit to share relevant information between agencies and a structure through which cases can be cross-referenced to have the most impact on a current investigation

UNG2 and RPA Activity on ssDNA-dsDNA Junctions

Uracil DNA glycosylase, or UNG2, is an enzyme that is involved in DNA repair. Its primary job is to eliminate harmful uracil bases from DNA strands. To do this, the enzyme is assisted by replication protein A (RPA). RPA helps UNG2 in the identification of uracil bases by targeting UNG2 activity near ssDNA-dsDNA junctions (1-3). The results from assays presented here agree with published findings that showed UNG2 is heavily targeted by RPA to uracil bases that are close to ssDNA-dsDNA junctions (for example, uracil located 9 bps from the junction as opposed to 33 bps) (1,2). However, these previous experiments were performed in the absence of a macromolecular crowding agent. Inert compounds such as PEG8K can be used experimentally to better represent the physiologic environment inside a cell, which is very crowded with proteins and other small molecules and differs from dilute conditions often used in enzyme assays. In the presence of a crowding agent (PEG8K), we found that RPA balances UNG2’s selectivity for uracil sites near ssDNA-dsDNA junctions that contain a 5’ ssDNA section. In other words, UNG2 becomes less targeted to uracils that are very close to the junction (i.e., U9). Interestingly, this effect was not seen when we examined RPA effects on UNG2 activity using ssDNA-dsDNA junctions substrates that contain a 3’ ssDNA section

Managing digital forensic knowledge an applied approach

The science of digital forensics is continually changing as technological advances are made and new digital devices are developed. This environment forces analysts to regularly extend their skills with training and frequent research to develop new and admissible techniques. Unfortunately, the same and similar methods are re-discovered by other analysts who are unaware of earlier peer efforts. The situation is aggravated by a nearly universal backlog in qualified digital forensics facilities. This leaves little time for communication between analysts even within a single agency. To address these issues and facilitate an increase in efficiency across all law enforcement agencies, we apply the lessons of knowledge management to digital forensics and extend them with special characteristics required by the law enforcement profession. The result is the development of the National Repository of Digital Forensic Intelligence. This system has been implemented in the largest accredited digital forensics lab in the world and is currently being extended to many other local, state, and federal agencies to increase effectiveness and efficiency among analysts