Examining the Functional Consequences of the Flexibility of Aminoglycoside Phosphotransferase (3’)-IIIa

The use of aminoglycoside antibiotics began in 1940 with the discovery of streptomycin. The overuse and misuse of antibiotics has resulted in prevalent cases of antibiotic resistance. The most common source of aminoglycoside resistance is the presence of enzymes that covalently modify the antibiotics at specific locations. One such enzyme, APH(3′)-IIIa [the aminoglycoside phosphotransferase three prime three a] conveys resistance by transferring the γ-phosphate [gamma phosphate] from ATP [adenosine triphosphate] onto the 3′ [three prime] carbon of the aminoglycoside antibiotic sugar ring. APH(3′)-IIIa has been shown to be flexible in solution and this flexibility is proposed to be responsible for its large substrate profile. Upon binding the aminoglycoside, APH(3′)-IIIa adopts a well-defined structure. All previous experiments were conducted in vitro. Here, various aspects associated with the flexibility of APH(3′)-IIIa are further examined in vivo. In-cell NMR [nuclear magnetic resonance] experiments are used to determine the protein dynamics of APH(3′)-IIIa in the crowded environment of the cell. Next, the flexibility of APH(3′)-IIIa is examined when binding more rigid aminoglycoside antibiotics: sisomicin and netilmicin in vitro

Person detection : unmanned system and small sensor applications

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2008.Includes bibliographical references (p. 97-99).The ability to quickly and reliably detect people in images and video is highly desired. Several object recognition algorithms have demonstrated successful detection of multiclass objects with varied scale, position and orientation. This study examines the effectiveness of these methods when applied to detecting humans in two distinct domains: A) Leave-behind sensing and B) Aerial surveillance. Using novel image sets that are significantly more realistic and difficult than standard datasets, a variety of tests are conducted to compare the algorithms in terms of classification success rate. Dalal and Triggs' Histogram of Oriented Gradients algorithm, when trained with image samples taken from inside MIT's Stata Center, detects with no false positives all but one person in six minutes of video taken from inside a separate building. An enhanced version of Riesenhuber and Poggio's cortex-like recognition model, trained to detect people, correctly classifies 95% of images taken from a small UAV when trained with an independent set of images. These results illustrate the potential to accurately and reliably determine the presence of people in video from unmanned aircraft and indoor sensors.by Paul Edward Rosendall.S.M

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations

Background:ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.Methods:Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.Results:In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; PConclusions:Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.</p

Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP (carbohydrate responsive element binding protein) locus and HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63599) and the UK Biobank (N=59220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (beta, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P<0.0001), but not significantly among the lowest SSB consumers (P=0.81; P-Diff<0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (beta, 0.06 [95% CI, 0.02-0.09] In-mg/dL per allele, P=0.001) but not the lowest SSB consumers (P=0.84; P-Diff=0.0005).CONCLUSIONS: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations.Clinical epidemiolog

Rebuilding community through the arts : a cultural planning toolkit for Indiana communities

There is no abstract available for this research paper.Thesis (M.U.R.P.)Department of Urban Plannin

Mathematical modeling of the pharyngeal phase of swallowing

Thesis (Ph. D.)--University of Washington, 1996A significant portion of the population suffers from difficulty in swallowing, known as dysphagia, including 12 to 13% of hospitalized patients and 40% of nursing home residents. Dysphagia can make it impossible for a person to eat and drink normally which can lead to malnutrition, cachexia, and dehydration. During the pharyngeal phase of swallowing, the food or liquid to be swallowed, known as the bolus, passes the entrance to the larynx. If the bolus penetrates into the larynx, aspiration or choking can occur. Chronic aspiration can lead to serious lung infections such as pneumonia. Approximately 8,000 people in the United States choke to death each year.In this research, a mathematical model that simulates swallowing was developed to analyze the parameters affecting the transport of the bolus through the pharynx. This work is a first attempt at modeling the pharyngeal phase of swallowing. The pharyngeal phase of swallowing is a complex, 3-dimensional, moving-boundary problem involving both fluid and solid motion. The model developed is a 2-dimensional representation of the fluid dynamics as the bolus passes through the pharynx. The mechanics of the pharyngeal muscle was not modeled, but was accounted for by prescribing the motion of the boundaries of the bolus in contact with the pharyngeal musculature. This boundary motion was found through image analysis of individual videofluoroscopy studies. The model was solved with a commercial computational fluid dynamics program, FIDAP.The model was applied to analyze data from a normal subject to investigate the effect of bolus volume, bolus viscosity, head positioning, and gravitational forces on the pharyngeal swallow. It was found that the viscosity had the greatest effect on the transport of the bolus through the pharynx. The most significant effect of modifying bolus volume or head positioning was to change the geometry of the bolus as it passed through the pharynx. Gravitational forces were found insignificant in the transport of the bolus except in the case of low-viscosity fluids.The effect of these parameters on swallowing disorders was also investigated by modifying the model and applying the same modeling techniques to data from a dysphagic subject. These studies provided insight into how laryngeal penetration can be reduced by modifying bolus properties

The Chemical Reactor Design Tool: a portable software package for education and reaction engineering

The Chemical Reactor Design Tool (CRDT) is a set of computer programs that solves the equations describing common chemical reactor models. The types of reactors that can be modeled include batch reactors, continuous stirred tank reactors, plug flow reactors, plug flow reactors with axial dispersion, and tubular flow reactors with radial dispersion. The models used are similar to those in the common reactor design textbooks. The most general equations describing the particular reactor are used for the base model so that any complexities can be included. CRDT is composed of three main components. The first is the window driven program that prompts the user for input. This input is required by the second component, the FORTRAN code that solves the mathematical models. The third componet: It is the set of programs that use the output from the FORTRAN programs to generate graphical output. CRDT can be used as a teaching tool. At the undergraduate level, complicated reactor models often cannot be solved by the student due to the complexity of the mathematics. CRDT allows the student to study such complex models without learning all of the required numerical techniques. Also, CRDT allows the student to compare many different models in a short amount of time. The effectiveness of using CRDT as a teaching tool is demonstrated with two examples from common reactor design textbooks. CRDT is also an effective design tool. It can be used to investigate many different phenomenon. The effects of axial and radial dispersion can be easily studied by comparing results of the PFR model with the results of the PFR with axial diffusion model and the two-dimensional model. Heterogeneous effects of catalyst packing can be analyzed by choosing external resistance under the mass transfer resistance menu and providing the appropriate parameters. Heat transfer at the wall can be included for all reactor types. Pressure drop for packed or empty tubes can be modeled. Corresponding changes in velocity and density are automatically taken into account for the gas-phase. Investigating all these effects allows the user to choose an appropriate model for their reaction system. A priori criterion can be used to estimate the importance of certain effects, but the predictions are not always accurate. The use of CRDT as a design tool is demonstrated by analyzing three industrial packed-bed reactors. The results are compared to the developed criteria