IPv6 tactical network management

Current and emerging technologies and equipment, such as unmanned aerial vehicles, ground sensors, networked radios, operator-worn sensor vests, and nanotechnology applications offer warfighters unprecedented command and control and information detection capabilities, yet the use of this technology has not been fully realized. The current protocol, IPv4, is incapable of providing enough addresses due to a depletion of IPv4 address space. IPv6, however, offers unprecedented network support for tactical-level sensor and communications assets in terms of increased address space, Quality of Service (QoS), flexibility, and security. The Department of Defense is transitioning from IPv4 to IPv6 in order to capitalize on IPv6's expanded capabilities. However, one unresolved area is proper IPv6 network management. Currently, the majority of the configuration and operational knowledge is in the mind of a very few individuals. The expertise currently available must be developed for application by the tactical network manager operating out on the edge of the network, in order to properly administer both an IPv4/IPv6 dual stacked network during the phased protocol transition and a purely native IPv6 network. Second, IPv6 features a robust Quality of Service (QoS) capability previously unavailable through IPv4, which requires research to determine the optimum configuration to support the warfighter's diverse requirements.http://archive.org/details/ipvtacticalnetwo109454574Outstanding ThesisUS Marine Corps (USMC) author.Approved for public release; distribution is unlimited

Interactive Similarity Analysis for 3D+t Cell Trajectory Data

Recent data acquisition techniques permit an improved analysis of living organisms. These techniques produce 3D+t information of cell developments in unprecedentedly high resolution. Biologists have a strong desire to analyze these cell evolutions in order to find similarities in their migration and division behaviors. The exploration of such patterns helps them in understanding how cells and hence organisms are able to ensure a regular shape development. However, the enormous size of the time-dependent data with several tens of thousands of cells and the need to analyze it in 3D hinder an interactive analysis. Visualizing the data to identify and extract relevant features provides a solution to this problem. For this, new visualization approaches are required that reduce the complexity of the data to detect important features in the visual analysis. In this thesis, novel visual similarity analysis methods are presented to interactively process very large 3D+t data of cell developments. Three main methods are developed that allow different visual analysis strategies. The usefulness of them is demonstrated by applications to cells from zebrafish embryos and Arabidopsis thaliana plants. Both data sets feature a high regularity in the shape formation of the organs and domain experts seek to research similar cell behaviors that are responsible for this development. For example, the identification of 3D division behaviors in plants is still an unresolved issue. The first method is a novel visualization approach that can automatically classify cell division types in plant data sets with high memory and time efficiency. The visualization is based on the generation of newly introduced cell isosurfaces that allow a quantitative and spatial comparison of cell division behaviors among individual plants. The method is applied to cells of the lateral root of Arabidopsis plants and reveals similar division schemes with respect to their temporal order. The second method enables a new visual similarity analysis for arbitrary 3D trajectory data in order to extract similar movement behaviors. The algorithm performs a grouping of thousands of trajectories with an optional level of detail modification. The clustering is based on a newly weighted combination of geometry and migratory features for which the weights are used to emphasize feature combinations. As a result, similar collective cell movements in zebrafish as well as a hitherto unknown correlation between division types and subsequent nuclei migrations in the Arabidopsis plants are detected. The third method is a novel visualization technique called the structure map. It permits a compact and interactive similarity analysis of thousands of binary tree structures. Unique trees are pre-ordered in the map based on spectral similarities and substructures are highlighted according to user-selected tree descriptors. Applied to cell developments from zebrafish depicted as trees, the map achieves compression rates up to 95% according to spectral analysis and facilitates an immediate identification of biologically implausible events and outliers. Additionally, similar quantities of feature appearances are detected in the center of the lateral root of several Arabidopsis plants

Profiling the Multi-omic Response to Mitochondrial Protease ClpP Activation in Triple-Negative Breast Cancer Cells

ONC201 and structural analogs (TR compounds) have been recently discovered as novel pharmacological activators of the mitochondrial protease ClpP. We were the first to publish the target of these compounds, as well as the ClpP-dependent induction of the integrated stress response (ATF4, CHOP). We have shown that the novel TR compounds are more potent than ONC201 at both in vitro activation of ClpP and growth inhibition in triple-negative breast cancer (TNBC) cells. Identification of significant mitochondrial effects following ONC201 treatment led us to investigate the effects of ONC201 and TR compounds on mitochondrial protein expression and oxidative phosphorylation, which we found to be significantly downregulated by pharmacological ClpP activation. Additionally, in vivo TR compound studies indicate a similar mechanism to effects observed in vitro (e.g., mtDNA and TFAM loss) while also being a well-tolerated treatment with optimized pharmacokinetic profiles, indicating potential for future clinical use. To investigate (1) the complete mechanism of action of ClpP activators leading to growth inhibition and (2) potential metabolic vulnerabilities generated by ClpP activation, multi-omic (proteomic, transcriptomic, and metabolomic) data was collected for TNBC cells following pharmacological ClpP activation. The multi-omic profile of these cells was analyzed using MetaCore, which revealed significant up- and downregulation across all three -omics datasets. Significantly perturbed pathways included amino acid, pyrimidine, citrulline, and heme biosynthesis, as well as tricarboxylic acid (TCA) cycle function. Identification of these perturbations confirms the multi-nodal effects of ClpP activation, as well as identifies potential metabolic vulnerabilities to be utilized in TR compound co-treatment development. This data can be further utilized in the future, as well as expanded upon, to elucidate the complete mechanism of action of ClpP activators on cell proliferation.Doctor of Philosoph

Conceptual design of a 10 to the 8th power bit magnetic bubble domain mass storage unit and fabrication, test and delivery of a feasibility model

The conceptual design of a highly reliable 10 to the 8th power-bit bubble domain memory for the space program is described. The memory has random access to blocks of closed-loop shift registers, and utilizes self-contained bubble domain chips with on-chip decoding. Trade-off studies show that the highest reliability and lowest power dissipation is obtained when the memory is organized on a bit-per-chip basis. The final design has 800 bits/register, 128 registers/chip, 16 chips/plane, and 112 planes, of which only seven are activated at a time. A word has 64 data bits +32 checkbits, used in a 16-adjacent code to provide correction of any combination of errors in one plane. 100 KHz maximum rotational frequency keeps power low (equal to or less than, 25 watts) and also allows asynchronous operation. Data rate is 6.4 megabits/sec, access time is 200 msec to an 800-word block and an additional 4 msec (average) to a word. The fabrication and operation are also described for a 64-bit bubble domain memory chip designed to test the concept of on-chip magnetic decoding. Access to one of the chip's four shift registers for the read, write, and clear functions is by means of bubble domain decoders utilizing the interaction between a conductor line and a bubble

Identity Management and Resource Allocation in the Network Virtualization Environment

Due to the existence of multiple stakeholders with conflicting goals and policies, alterations to the existing Internet architecture are now limited to simple incremental updates; deployment of any new, radically different technology is next to impossible. To fend off this ossification, network virtualization has been propounded as a diversifying attribute of the future inter-networking paradigm. In this talk, we provide an overview of the network virtualization environment (NVE) and address two basic problems in this emerging field of networking research. The identity management problem is primarily concerned with ensuring interoperability across heterogeneous identifier spaces for locating and identifying end hosts in different virtual networks. We describe the architectural and the functional components of a novel identity management framework (iMark) that enables end-to-end connectivity across heterogeneous virtual networks in the NVE without revoking their autonomy. The virtual network embedding problem deals with the mapping of virtual nodes and links onto physical network resources. We argue that the separation of the node mapping and the link mapping phases in the existing algorithms considerably reduces the solution space and degrades embedding quality. We propose coordinated node and link mapping to devise two algorithms (D-ViNE and R-ViNE) for the online version of the problem under realistic assumptions and compare their performance with the existing heuristics

Mechanistic and synthetic studies on the prochlorosin and cytolysin families of lanthipeptides

Peptides are an attractive class of therapeutics, occupying a niche between small molecules and biologics. Research in the van der Donk lab focuses on lanthipeptides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that commonly feature antibacterial activity and contain the characteristic thioether residues lanthionine (Lan) and methyllanthionine (MeLan). Installation of thioether crosslinks in lanthipeptide biosynthesis is carried out by designated synthetases and involves dehydration of Ser/Thr residues and cyclization via Michael-type addition. The remarkably broad substrate scope of the synthetase ProcM inspired us to explore its mechanism in detail (chapter 2). My studies on ProcM revealed the directionality of dehydration, the order of cyclization, and that, despite the impressive substrate scope, none of the cyclizations are non-enzymatic. In collaboration, we established the irreversibility of the Michael-type addition and proposed that the topology of the thioether rings is under kinetic control. Solid phase peptide synthesis (SPPS) was used to generate the substrates to study ProcM, and is also a flexibile tool to access non-native lanthipeptide analogues. Interestingly, a lanthipeptide, cytolysin S (CylLS”), exhibited cytolytic activity in synergy with cytolysin L (CylLL”). Given that a thioether crosslink in CylLS” has an unusual LL-stereochemistry, the synthesis of a diastereomer of CylLS” with the more common DL-stereochemistry was achieved by SPPS (chapter 3). We probed whether the cytolytic activity depended on the LL-stereochemistry observed in CylLS”. Surprisingly, the unusual LL-stereochemistry was found to be important for the antibacterial activity, but not necessary for the hemolytic activity of CylLS”. I have also synthesized another hydrophobic lanthipeptide analogue, the portion of microbisporicin that contains the A and B ring (chapter 4). We established that this motif is not recognized by the halogenase MibH, and that the C terminus of microbisporicin is necessary for the chlorination by MibH. During my graduate studies, I had the opportunity to collaborate in a different area of research in our laboratory, the phosphonates. My efforts in the syntheses of various substrates and intermediates were instrumental in elucidating the biosynthetic pathways of dehydrophos, fosfazinomycin, and rhizocticin (chapter 5)

The characterisation and analysis of in-situ and blasted block-size distributions and the blastability of rock masses.

PhDIn this thesis, previous research on discontinuity geometry, in-situ block size distribution (IBSD), blasted block size distribution (BBSD), and blastability of rock mass is discussed. The IBSD with special reference to discontinuities with a fractal spacing distribution is investigated using computer simulation, from which a set of empirical equations is derived for predicting the IBSD of a rock mass with discontinuities of fractal spacing distributions. The goodness-of-fit of theoretical as compared with real spacing distributions is discussed and a grey correlation analysis technique is introduced into the goodness-of-fit. An estimation of mean trace length of discontinuities with lognormal and fractal distributions is derived. A numerical algorithm and associated computer program for estimating the discontinuity size distribution is developed from which empirical equations for estimating the mean size of discontinuities with negative exponential, lognormal and fractal trace length distributions have been derived. A factor which accounts for the discontinuity impersistence is incorporated into the estimation of IBSD. Combining both Ross-Ram and Schuhmann models, a reasonably accurate and user-friendly "photo-scanline" technique is devised for the estimation of BBSD of the blastpile. Blasting results, as a function of both the intact rock properties and the discontinuity structures are investigated, and an energy-block-transition model characterising the blastability of rock masses is developed. It is argued that the blastability of rock mass is governed by a comprehensive range of both intact rock properties and discontinuity parameters, and that the fractal dimension of the IBSD of a rock mass could be an indicator of blastability. Taking into account that blastability is a complex property, a methodology of assessing blastability of rock masses is introduced using a Rock Engineering Systems method. Published data from the literature has been used wherever possible to support the validation of the new techniques of analysis and two case histories in which applications of the developed methodologies and techniques are presented