Binding of Bisbenzamidines with AT Rich DNA: A Thermodynamic Study

Diamidines are small molecules that generally possess antiparasitic properties and bind preferentially to the minor groove of AT rich DNA. With the goal of getting a better understanding of the thermodynamic driving forces and binding affinities, a series of pentamidine analogs were investigated with various AT rich DNA by ITC, UV-Vis and fluorescence spectroscopic methods. Findings suggest that the substitution of the linker oxygen of pentamidine to a nitrogen slightly improves the binding affinity. All of the investigated compounds are entropically driven at 25 oC with non-alternating AT DNA. Additionally, the increased fluorescence of the nitrogen and sulfur linked analogs will enable future work to be done with fluorescence microscopy to help determine if and where these compounds accumulate in the target organism

A Generic Intelligent Architecture for Computer-Aided Training of Procedural Knowledge

Intelligent Tutoring System (ITS) development is a knowledge-intensive task, suffering from the same knowledge acquisition bottleneck that plagues most Artificial Intelligence (AI) systems. This research presents an architecture that requires knowledge only in the form of a shallow knowledge base and a simulation to produce a training system. The knowledge base provides the basic procedural knowledge while the simulation provides context. The remainder of the knowledge required for training is learned through the interaction of these components in a state-space scenario exploration process and inductive machine learning. These knowledge components are used only at the interface level, allowing the internal representation to take any form that meets the interface requirements. A prototype of this architecture is implemented as a proof-of-concept to illustrate the viability of the key knowledge acquisition techniques

Anthropogenic impacts on mosquito populations in North America over the past century.

The recent emergence and spread of vector-borne viruses including Zika, chikungunya and dengue has raised concerns that climate change may cause mosquito vectors of these diseases to expand into more temperate regions. However, the long-term impact of other anthropogenic factors on mosquito abundance and distributions is less studied. Here, we show that anthropogenic chemical use (DDT; dichlorodiphenyltrichloroethane) and increasing urbanization were the strongest drivers of changes in mosquito populations over the last eight decades in areas on both coasts of North America. Mosquito populations have increased as much as tenfold, and mosquito communities have become two- to fourfold richer over the last five decades. These increases are correlated with the decay in residual environmental DDT concentrations and growing human populations, but not with temperature. These results illustrate the far-reaching impacts of multiple anthropogenic disturbances on animal communities and suggest that interactions between land use and chemical use may have unforeseen consequences on ecosystems

The Impact of Transit Corridors on Residential Property Values

Most of the literature on transit corridors, such as superhighways and tunnels, focuses on the positive externality of transit access (e.g., interstate access, transit station) and fails to isolate the negative externality of the corridor itself. This empirical study examines two situations: one with both access benefits and negatives, and another without the access benefit. The findings reveal that proximity to the transit corridor alone without direct access conveys a negative impact on nearby housing values.

Fluid quantity gaging

A system for measuring the mass of liquid in a tank on orbit with 1 percent accuracy was developed and demonstrated. An extensive tradeoff identified adiabatic compression as the only gaging technique that is independent of gravity or its orientation, and of the size and distribution of bubbles in the tank. This technique is applicable to all Earth-storable and cryogenic liquids of interest for Space Station use, except superfluid helium, and can be applied to tanks of any size, shape, or internal structure. Accuracy of 0.2 percent was demonstrated in the laboratory, and a detailed analytical model was developed and verified by testing. A flight system architecture is presented that allows meeting the needs of a broad range of space fluid systems without custom development for each user

The effect of the GLP-1 analogue Exenatide on functional connectivity within an NTS-based network in women with and without obesity.

ObjectiveThe differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity.MethodsFollowing an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug-induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus.ResultsWomen with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese.ConclusionsObesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP-1 analogues in therapeutic interventions

Altered functional connectivity within the central reward network in overweight and obese women.

Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors

Role of brain imaging in disorders of brain-gut interaction: a Rome Working Team Report.

Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required