Kinematic and cyclostationary parameter estimation for co-channel emitter location applications

The problem of locating a signal source, or an emitter, has many civilian and military applications, such as communication regulations enforcement, military reconnaissance, and search-and-rescue operations. Many of the most widely used emitter location methods rely on the accurate and robust estimation of the differential time delay, or time-difference-of-arrival (TDOA), and the differential Doppler shift, or frequency- difference-of-arrival (FDOA), between signal replicas arriving at two spatially separated receivers. There are many conventional methods for estimating TDOA and/or FDOA. However, these methods are unable to produce unbiased TDOA and FDOA estimates when multiple emitters are located spatially close to each other. In many cases, the spatial proximity at which the conventional methods fail is still unacceptably large for precision emitter location applications. This problem is made even more diffcult when separating signals from multiple emitters that share the same regions of the spectrum at the same time. When spatially close emitters overlap spectrally and temporally, robust TDOA and FDOA estimation is diffcult, and accurate emitter location not only requires both estimation of TDOA, or FDOA, or both jointly, but also the estimation of a signal parameter that can be used to separate the signal-of-interest (SOI) from a signal(s)-not-of-interest (SNOI) that are both within the receiver's field of view. The signal separation pa- rameter selected depends on the type of signal modulation. In this thesis, the signals of interest are bauded signals. The separation methodology for such signals is cyclo- stationarity with parameterization by cyclic frequency. Based on this assumption, a new three-dimensional joint estimation method for TDOA, FDOA, and cyclic frequency parameters, called alpha cross ambiguity function (alpha-CAF), has been developed to ex- ploit signal modulations with cyclostationary properties. By exploiting cyclostationarity, alppha-CAF can produce separate unbiased TDOA and FDOA estimates that will in turn yield reliable geolocation estimates for precision emitter location applications even when severe interference causes conventional methods to fail. In this thesis the alpha-CAF param- eter estimation (TDOA, FDOA, Cyclic Frequency) algorithm is introduced along with a complete analysis of its performance compared to conventional estimators. A connection is also made between the alpha-CAF algorithm and the additional steps needed to perform an emitter location technique

Ant-infecting Ophiocordyceps genomes reveal a high diversity of potential behavioral manipulation genes and a possible major role for enterotoxins

Much can be gained from revealing the mechanisms fungal entomopathogens employ. Especially intriguing are fungal parasites that manipulate insect behavior because, presumably, they secrete a wealth of bioactive compounds. To gain more insight into their strategies, we compared the genomes of five ant-infecting Ophiocordyceps species from three species complexes. These species were collected across three continents, from five different ant species in which they induce different levels of manipulation. A considerable number of (small) secreted and pathogenicity-related proteins were only found in these ant-manipulating Ophiocordyceps species, and not in other ascomycetes. However, few of those proteins were conserved among them, suggesting that several different methods of behavior modification have evolved. This is further supported by a relatively fast evolution of previously reported candidate manipulation genes associated with biting behavior. Moreover, secondary metabolite clusters, activated during biting behavior, appeared conserved within a species complex, but not beyond. The independent co-evolution between these manipulating parasites and their respective hosts might thus have led to rather diverse strategies to alter behavior. Our data indicate that specialized, secreted enterotoxins may play a major role in one of these strategies

Here We Come Ready or Not: Occupational Therapy Program to Help Prepare Prisoners for Reentry into Society

poster abstractAbstract Background: In 2013 about 10 million people were involved in various stages of imprisonment world-wide. In that same year there were about 1,574,700 persons in state and federal prisons in the United States, and 29,905 in Indiana (state and federal) prisons. Most of those people will return to society, but for how long? According to the most recent data available, a little over two-thirds (67.8%) of those released were arrested for a new crime within 3 years and over three-quarters (76.6%) were arrested for a new crime within 5 years. Education is one of the most effective reducers of recidivism, but it is unclear what kinds of education best prepare people to not only return to society, but to thrive in society. Objectives: The first of a two-part study explored how 27 residents of a minimum security prison responded to an Occupational Therapy Community Living Skills Program (OTCLS) developed to help prepare residents for successful reentry into society. Method: Using a participatory action research (PAR) approach, we interviewed 27 residents who completed the program. Once the semi-structured interviews were transcribed, the PAR team conducted a summative content analysis of the data. Results: Initial content analysis yielded five concepts: doing; information; re-entry fears (socialization); technology; and self-worth. Participants seemed to gain a sense of self-worth by doing activities related to information gathering, socialization, and technology. Further interpretation yielded three overlapping themes: 1) validation of self-worth (participants expressed how self-validating it is to have “real people” come in to help), 2) doing (role playing, a common activity, “…was kind of nerve-wracking at first then [I] began to slowly ease into it…”), and 3) concerns about the future (one resident summed up the value of the program: having “…something real positive you’re looking forward to…helps in dissipating the fears perhaps in reentry.”). Conclusions: This retrospective study identified potentially powerful elements of a successful re-entry program. In the second part of the study we will evaluate a revised program using a pre-test; post-test and follow-up approach to learn more about what kinds of education best prepare people to not only return to society, but to thrive in society

Catalytic Enantioselective Synthesis of Tetrahydocarbazoles and Exocyclic Pictet-Spengler-Type Reactions

A synthetic strategy for the synthesis of chiral tetrahydrocarbazoles (THCAs) has been developed. The strategy relies on two types of 6-<i>exo-trig</i> cyclization of 3-substituted indole substrates. Enantioselective domino Friedel–Crafts-type reactions leading to THCAs can be catalyzed by chiral phosphoric acid derivatives (with up to >99% ee), and the first examples of exocyclic Pictet–Spengler reactions to form THCAs are reported

Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening

Leishmaniasis is a neglected disease that is caused by different species of the protozoan parasite Leishmania, and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this parasitic disease. One pathway that has been genetically validated as an antileishmanial drug target is the biosynthesis of uridine diphosphate-glucose (UDP-Glc), and its direct derivative UDP-galactose (UDP-Gal). De novo biosynthesis of these two nucleotide sugars is controlled by the specific UDP-glucose pyrophosphorylase (UGP). Leishmania parasites additionally express a UDP-sugar pyrophosphorylase (USP) responsible for monosaccharides salvage that is able to generate both UDP-Gal and UDP-Glc. The inactivation of the two parasite pyrophosphorylases UGP and USP, results in parasite death. The present study reports on the identification of structurally diverse scaffolds for the development of USP inhibitors by fragment library screening. Based on this screening, we selected a small set of commercially available compounds, and identified molecules that inhibit both Leishmania major USP and UGP, with a half-maximal inhibitory concentration in the 100 &micro;M range. The inhibitors were predicted to bind at allosteric regulation sites, which were validated by mutagenesis studies. This study sets the stage for the development of potent USP inhibitors

Organic component vapor pressures and hygroscopicities of aqueous aerosol measured by optical tweezers

Measurements of the hygroscopic response of aerosol and the particle-to-gas partitioning of semivolatile organic compounds are crucial for providing more accurate descriptions of the compositional and size distributions of atmospheric aerosol. Concurrent measurements of particle size and composition (inferred from refractive index) are reported here using optical tweezers to isolate and probe individual aerosol droplets over extended timeframes. The measurements are shown to allow accurate retrievals of component vapor pressures and hygroscopic response through examining correlated variations in size and composition for binary droplets containing water and a single organic component. Measurements are reported for a homologous series of dicarboxylic acids, maleic acid, citric acid, glycerol, or 1,2,6-hexanetriol. An assessment of the inherent uncertainties in such measurements when measuring only particle size is provided to confirm the value of such a correlational approach. We also show that the method of molar refraction provides an accurate characterization of the compositional dependence of the refractive index of the solutions. In this method, the density of the pure liquid solute is the largest uncertainty and must be either known or inferred from subsaturated measurements with an error of <±2.5% to discriminate between different thermodynamic treatments. (Chemical Equation Presented)

The impact of methodology on the reproducibility and rigor of DNA methylation data

Epigenetic modifications are crucial for normal development and implicated in disease pathogenesis. While epigenetics continues to be a burgeoning research area in neuroscience, unaddressed issues related to data reproducibility across laboratories remain. Separating meaningful experimental changes from background variability is a challenge in epigenomic studies. Here we show that seemingly minor experimental variations, even under normal baseline conditions, can have a significant impact on epigenome outcome measures and data interpretation. We examined genome-wide DNA methylation and gene expression profiles of hippocampal tissues from wild-type rats housed in three independent laboratories using nearly identical conditions. Reduced-representation bisulfite sequencing and RNA-seq respectively identified 3852 differentially methylated and 1075 differentially expressed genes between laboratories, even in the absence of experimental intervention. Difficult-to-match factors such as animal vendors and a subset of husbandry and tissue extraction procedures produced quantifiable variations between wild-type animals across the three laboratories. Our study demonstrates that seemingly minor experimental variations, even under normal baseline conditions, can have a significant impact on epigenome outcome measures and data interpretation. This is particularly meaningful for neurological studies in animal models, in which baseline parameters between experimental groups are difficult to control. To enhance scientific rigor, we conclude that strict adherence to protocols is necessary for the execution and interpretation of epigenetic studies and that protocol-sensitive epigenetic changes, amongst naive animals, may confound experimental results

Apolipoprotein E ε4 and Later-Life Decline in Cognitive Function and Grip Strength.

Objectives: Presence of the apolipoprotein E (APOE) ε4 allele is a risk factor for dementia, whereas the ε2 allele offers protection against dementia. There is also evidence for a relationship between APOE genotype and changes in cognitive function. It is not clear, however, whether this relationship stems from undetected disease in persons genetically more vulnerable to dementia. This study examined whether APOE genotype was associated with either initial performance or change in performance on a range of cognitive and noncognitive tasks, after accounting for possible preclinical dementia. Design: A population-based cohort was assessed up to four times over 12 years. Participants: The sample was an Australian cohort of 590 participants age 70 years and older who were genotyped for APOE. Measurements: The outcomes were processing speed, verbal fluency, episodic memory, word recognition, face recognition, grip strength, and reaction time. Results: Adjusted latent growth models indicated that ε4 carriers had significantly poorer initial memory performance and greater declines in processing speed and word recognition than ε2 and ε3 carriers. In addition, ε2 carriers exhibited significantly less decline in right grip strength than ε3 carriers. However, after excluding 125 participants with low global cognition scores, all genotype effects became nonsignificant. Conclusions: Over a 12-year period, findings indicate that APOE ε4-related cognitive decline in older community-dwelling populations is due to a higher likelihood of preclinical dementia among ε4 carriers. When possible dementia cases are removed from the analyses, ε4 associations with cognitive decline become statistically unreliable