Algorithms for autonomous tandem operation of a dual M113 system

In mid-July 2003, the U.S. Army Tank-Automotive & Armaments Command (TACOM) performed a series of experiments at Keweenaw Research Center (KRC), with a remote operated mine roller system. This system, named Panther Lite, consists of two M113 Armored Personnel Carriers (APC’s) connected by a Tandem Vehicle Linkage Assembly (TVLA). The system has three sets of mine rollers, two of which are connected to the front of the lead vehicle with one set trailing from the trail vehicle. Currently, the system requires two joystick controllers. One regulates the braking of the tracks, throttle, and transmission of the lead vehicle and the other controls the braking and throttle of the rear vehicle. One operator controls both joysticks, attempting to maneuver the lead vehicle along a desired path. At the same time, this operator makes compensation maneuvers to reduce lateral loads in the TVLA and to guide the rear mine rollers along the desired path. The purpose of this project is to create algorithms that would allow the slave (trail) vehicle to operate using inputs that maneuver the control (lead) vehicle. The project will be completed by first reconstructing the experimental data. Kinematic models will be generated and simulations created. The models will then be correlated with the reconstructions of the experimental data. The successful completion of this project will be a first step to eliminating the need for the second joystick.

Composing in words and images : a proposal for a tandem approach to written and visual composition pedagogy

This project proposes a module for teaching visual composition within the context of a written composition course. Drawing from process writing theory, critical pedagogy, and photo-elicitation, “Composing In Words And Images” gives composition teachers a module and direct instruction for the incorporation of critical visual composition studies in their writing classes.

TanDEM-X High Resolution DEMs and Their Applications to Flow Modeling

Lava flow modeling can be a powerful tool in hazard assessments; however, the ability to produce accurate models is usually limited by a lack of high resolution, up-to-date Digital Elevation Models (DEMs). This is especially obvious in places such as Kilauea Volcano (Hawaii), where active lava flows frequently alter the terrain. In this study, we use a new technique to create high resolution DEMs on Kilauea using synthetic aperture radar (SAR) data from the TanDEM-X (TDX) satellite. We convert raw TDX SAR data into a geocoded DEM using GAMMA software [Werner et al., 2000]. This process can be completed in several hours and permits creation of updated DEMs as soon as new TDX data are available. To test the DEMs, we use the Harris and Rowland [2001] FLOWGO lava flow model combined with the Favalli et al. [2005] DOWNFLOW model to simulate the 3-15 August 2011 eruption on Kilauea's East Rift Zone. Results were compared with simulations using the older, lower resolution 2000 SRTM DEM of Hawaii. Effusion rates used in the model are derived from MODIS thermal infrared satellite imagery. FLOWGO simulations using the TDX DEM produced a single flow line that matched the August 2011 flow almost perfectly, but could not recreate the entire flow field due to the relatively high DEM noise level. The issues with short model flow lengths can be resolved by filtering noise from the DEM. Model simulations using the outdated SRTM DEM produced a flow field that followed a different trajectory to that observed. Numerous lava flows have been emplaced at Kilauea since the creation of the SRTM DEM, leading the model to project flow lines in areas that have since been covered by fresh lava flows. These results show that DEMs can quickly become outdated on active volcanoes, but our new technique offers the potential to produce accurate, updated DEMs for modeling lava flow hazards.

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of SN2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl2, trigger a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.

Splitting of a prevalent Mycobacterium bovis spoligotype by variable-number tandem-repeat typing reveals high heterogeneity in an evolving clonal group

Mycobacterium bovis populations in countries with persistent bovine tuberculosis usually show a prevalent spoligotype with a wide geographical distribution. This study applied mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing to a random panel of 115 M. bovis isolates that are representative of the most frequent spoligotype in the Iberian Peninsula, SB0121. VNTR typing targeted nine loci: ETR-A (alias VNTR2165), ETR-B (VNTR2461), ETR-D (MIRU4, VNTR580), ETR-E (MIRU31, VNTR3192), MIRU26 (VNTR2996), QUB11a (VNTR2163a), QUB11b (VNTR2163b), QUB26 (VNTR4052), and QUB3232 (VNTR3232). We found a high degree of diversity among the studied isolates (discriminatory index [D] = 0.9856), which were split into 65 different MIRU-VNTR types. An alternative short-format MIRU-VNTR typing targeting only the four loci with the highest variability values was found to offer an equivalent discriminatory index. Minimum spanning trees using the MIRU-VNTR data showed the hypothetical evolution of an apparent clonal group. MIRU-VNTR analysis was also applied to the isolates of 176 animals from 15 farms infected by M. bovis SB0121; in 10 farms, the analysis revealed the coexistence of two to five different MIRU types differing in one to six loci, which highlights the frequency of undetected heterogeneity.

A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients

Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC–MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization–triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-13C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter-day CV%: 3–6.3%) and accurate (3.8–7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, −20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service.

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Evaluating the Quality and Accuracy of TanDEM-X Digital Elevation Models at Archaeological Sites in the Cilician Plain, Turkey

Satellite remote sensing provides a powerful instrument for mapping and monitoring traces of historical settlements and infrastructure, not only in distant areas and crisis regions. It helps archaeologists to embed their findings from field surveys into the broader context of the landscape. With the start of the TanDEM-X mission, spatially explicit 3D-information is available to researchers at an unprecedented resolution worldwide. We examined different experimental TanDEM-X digital elevation models (DEM) that were processed from two different imaging modes (Stripmap/High Resolution Spotlight) using the operational alternating bistatic acquisition mode. The quality and accuracy of the experimental DEM products was compared to other available DEM products and a high precision archaeological field survey. The results indicate the potential of TanDEM-X Stripmap (SM) data for mapping surface elements at regional scale. For the alluvial plain of Cilicia, a suspected palaeochannel could be reconstructed. At the local scale, DEM products from TanDEM-X High Resolution Spotlight (HS) mode were processed at 2 m spatial resolution using a merge of two monostatic/bistatic interferograms. The absolute and relative vertical accuracy of the outcome meet the specification of high resolution elevation data (HRE) standards from the National System for Geospatial Intelligence (NSG) at the HRE20 level.

Elucidation of Nucleic Acid–Drug Interactions by Tandem Mass Spectrometry

In continuation of the long tradition of mass spectrometric research at the University of Bern, our group focuses on the characterization of nucleic acids as therapeutic agents and as drug targets. This article provides a short overview of our recent work on platinated single-stranded and higher-order nucleic acids. Nearly three decades ago the development of soft ionization techniques opened a whole new chapter in the mass spectrometric analysis of not only nucleic acids themselves, but also their interactions with potential drug candidates. In contrast to modern next generation sequencing approaches, though, the goal of the tandem mass spectrometric investigation of nucleic acids is by no means the complete sequencing of genetic DNA, but rather the characterization of short therapeutic and regulatory oligonucleotides and the elucidation of nucleic acid–drug interactions. The influence of cisplatin binding on the gas-phase dissociation of nucleic acids was studied by the means of electrospray ionization tandem mass spectrometry. Experiments on native and modified DNA and RNA oligomers confirmed guanine base pairs as the preferred platination site and laid the basis for the formulation of a gas-phase fragmentation mechanism of platinated oligonucleotides. The study was extended to double stranded DNA and DNA quadruplexes. While duplexes are believed to be the main target of cisplatin in vivo, the recently discovered DNA quadruplexes constitute another promising target for anti-tumor drugs owing to their regulatory functions in the cell cycle.

Electrospray tandem mass spectrometry of mixed-sequence RNA/DNA oligonucleotides

The fragmentation of electrospray-generated multiply deprotonated RNA and mixed-sequence RNA/DNA pentanucleotides upon low-energy collision-induced dissociation (CID) in a hybrid quadrupole time-of-flight mass spectrometer was investigated. The goal of unambiguous sequence identification of mixed-sequence RNA/DNA oligonucleotides requires detailed understanding of the gas-phase dissociation of this class of compounds. The two major dissociation events, base loss and backbone fragmentation, are discussed and the unique fragmentation behavior of oligoribonucleotides is demonstrated. Backbone fragmentation of the all-RNA pentanucleotides is characterized by abundant c-ions and their complementary y-ions as the major sequence-defining fragment ion series. In contrast to the dissociation of oligodeoxyribonucleotides, where backbone fragmentation is initiated by the loss of a nucleobase which subsequently leads to the formation of the w- and [a-base]-ions, backbone dissociation of oligoribonucleotides is essentially decoupled from base loss. The different behavior of RNA and DNA oligonucleotides is related to the presence of the 2'-hydroxyl substituent, which is the only structural alteration between the DNA and RNA pentanucleotides studied. CID of mixed-sequence RNA/DNA pentanucleotides results in a combination of the nucleotide-typical backbone fragmentation products, with abundant w-fragment ions generated by cleavage of the phosphodiester backbone adjacent to the deoxy building blocks, whereas backbone cleavage adjacent to ribonucleotides induces the formation of c- and y-ions. (C) 2002 American Society for Mass Spectrometry.