Instability of CTG Repeats is Governed by the Position of a DNA Base Lesion through Base Excision Repair

Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base lesion in the repeat tract. A lesion located at the 59-end of CTG repeats resulted in expansion, whereas a lesion located either in the middle or the 39-end of the repeats led to deletions only. The positioning effects appeared to be determined by the formation of hairpins at various locations on the template and the damaged strands that were bypassed by DNA polymerase b and processed by flap endonuclease 1 with different efficiency. Our study indicates that the position of a DNA base lesion governs whether TNR is expanded or deleted through BER.

Pioneers in the study of motion

From the multitudinous streets of Mexico City through the lonely highways of the United States, this collection of poetry charts strategies of representation across complex territories of culture and gender. These poems represent dialogues and negotiations with popular and poetic narratives of the Americas, as well as individual quests for identification against a backdrop of postmodern and postcolonial concerns. The effect is like that of a collage that elicits the reader's participation in order to produce individual signification. The figures alluded to in these pieces enact the struggle to situate the self within multiple registers of discourse and identity, as well as to establish a site from which to speak.

Investigating Miami English-Spanish Bilinguals' Treatment of English Deictic Verbs of Motion

This investigation focused on the treatment of English deictic verbs of motion by Spanish-English bilinguals in Miami. Although English and Spanish share significant overlap of the spatial deixis system, they diverge in important aspects. It is not known how these verbs are processed by bilinguals. Thus, this study examined Spanish-English bilinguals’ interpretation of the verbs come, go, bring, and take in English. Forty-five monolingual English speakers and Spanish-English bilinguals participated. Participants were asked to watch video clips depicting motion events and to judge the acceptability of accompanying narrations spoken by the actors in the videos. Analyses showed that, in general, monolinguals and bilinguals patterned similarly across the deictic verbs come, bring, go and take. However, they did differ in relation to acceptability of word order for verbal objects. Also, bring was highly accepted by all language groups across all goal paths, possibly suggesting an innovation in its use.

Reliability of the Clinical Application of a Mechanical Inclinometer in Measuring Glenohumeral Motion

Objective: Establish intra- and inter-examiner reliability of glenohumeral range of motion (ROM) measures taken by a single-clinician using a mechanical inclinometer. Design: A single-session, repeated-measure, randomized, counterbalanced design. Setting: Athletic Training laboratory. Participants: Ten college-aged volunteers (9 right-hand dominant; 4 males, 6 females; age=23.2±2.4y, mass=73±16kg, height=170±8cm) without shoulder or neck injuries within one year. Interventions: Two Certified Athletic Trainers separately assessed passive glenohumeral (GH) internal (IR) and external (ER) rotation bilaterally. Each clinician secured the inclinometer to each subject’s distal forearm using elastic straps. Clinicians followed standard procedures for assessing ROM, with the participants supine on a standard treatment table with 90° of elbow flexion. A second investigator recorded the angle. Clinicians measured all shoulders once to assess inter-clinician reliability and eight shoulders twice to assess intra-clinician reliability. We used SPSS 14.0 (SPSS Inc., Chicago, IL) to calculate standard error of measure (SEM) and Intraclass Correlation Coefficients (ICC) to evaluate intra- and inter-clinician reliability. Main Outcome Measures: Dependent variables were degrees of IR, ER, glenohumeral internal rotation deficit (GIRD) and total arc of rotation. We calculated GIRD as the bilateral difference in IR (nondominant–dominant) and total arc for each shoulder (IR+ER). Results: Intra-clinician reliability for each examiner was excellent (ICC[1,1] range=0.90-0.96; SEM=2.2°-2.5°) for all measures. Examiners displayed excellent inter-clinician reliability (ICC[2,1] range=0.79-0.97; SEM=1.7°-3.0°) for all measures except nondominant IR which had good reliability(0.72). Conclusions: Results suggest that clinicians can achieve reliable measures of GH rotation and GIRD using a single-clinician technique and an inexpensive, readily available mechanical inclinometer.

Optimization of pavement maintenance and rehabilitation programming using shuffled complex evolution algorithm

The major barrier to practical optimization of pavement preservation programming has always been that for formulations where the identity of individual projects is preserved, the solution space grows exponentially with the problem size to an extent where it can become unmanageable by the traditional analytical optimization techniques within reasonable limit. This has been attributed to the problem of combinatorial explosion that is, exponential growth of the number of combinations. The relatively large number of constraints often presents in a real-life pavement preservation programming problems and the trade-off considerations required between preventive maintenance, rehabilitation and reconstruction, present yet another factor that contributes to the solution complexity. In this research study, a new integrated multi-year optimization procedure was developed to solve network level pavement preservation programming problems, through cost-effectiveness based evolutionary programming analysis, using the Shuffled Complex Evolution (SCE) algorithm.^ A case study problem was analyzed to illustrate the robustness and consistency of the SCE technique in solving network level pavement preservation problems. The output from this program is a list of maintenance and rehabilitation treatment (M&R) strategies for each identified segment of the network in each programming year, and the impact on the overall performance of the network, in terms of the performance levels of the recommended optimal M&R strategy. ^ The results show that the SCE is very efficient and consistent in the simultaneous consideration of the trade-off between various pavement preservation strategies, while preserving the identity of the individual network segments. The flexibility of the technique is also demonstrated, in the sense that, by suitably coding the problem parameters, it can be used to solve several forms of pavement management programming problems. It is recommended that for large networks, some sort of decomposition technique should be applied to aggregate sections, which exhibit similar performance characteristics into links, such that whatever M&R alternative is recommended for a link can be applied to all the sections connected to it. In this way the problem size, and hence the solution time, can be greatly reduced to a more manageable solution space. ^ The study concludes that the robust search characteristics of SCE are well suited for solving the combinatorial problems in long-term network level pavement M&R programming and provides a rich area for future research. ^

Mechanistic studies on the degradation of gasoline oxygenates by advanced oxidation technologies and the reaction of 4-methyl-1,2,4-triazoline-3,5-dione with tetracyclopropylethylene

Gasoline oxygenates (MTBE, methyl tert-butyl ether; DIPE, di-isopropyl ether; ETBE, ethyl tert-butyl ether; TAME, tert-amyl ether) are added to gasoline to boost octane and enhance combustion. The combination of large scale use, high water solubility and only minor biodegradability has now resulted in a significant gasoline oxygenate contamination occurring in surface, ground, and drinking water systems. Combination of hydroxyl radical formation and the pyrolytic environment generated by ultrasonic irradiation (665 kHz) leads to the rapid degradation of MTBE and other gasoline oxygenates in aqueous media. ^ The presence of oxygen promotes the degradation processes by rapid reaction with carbon centered radicals indicating radical processes involving O 2 are significant pathways. A number of the oxidation products were identified. The formation of products (alcohols, ketones, aldehydes, esters, peroxides, etc) could be rationalized by mechanisms which involve hydrogen abstraction by OH radical and/or pyrolysis to form carboncentered radicals which react with oxygen and follow standard oxidation chain processes. ^ The reactions of N-substituted R-triazolinediones (RTAD; R = CH 3 or phenyl) have attracted considerable interest because they exhibit a number of unusual mechanistic characteristics that are analogous to the reactions of singlet oxygen (1O2) and offer an easy way to provide C-N bond(s) formation. The reactions of triazolinedione with olefins have been widely studied and aziridinium imides are generally accepted to be the reactive intermediates. ^ We observed the rapid formation of an unusual intermediate upon mixing tetracyclopropylethylene with 4-methyl-1,2,4-triazoline-3,5-dione in CDCl 3. Detailed characterization by NMR (proton, 13C, 2-D NMRs) indicates the intermediate is 5,5,6,6-tetracyclopropyl-3-methyl-5,6-dihydro-oxazolo[3,2- b][1,2,4]-triazolium-2-olate. Such products are extremely rare and have not been studied. Upon warming the intermediate is converted to 2 + 2 diazetidine (major) and ene product (minor). ^ To further explore the kinetics and dynamics of the reaction activation energies were obtained using Arrhenius plots. Activation energies for the formation of the intermediate from reactants, and 2+2 adduct from the intermediate were determined as 7.48 kcal moll and 19.8 kcal mol−1 with their pre-exponential values of 2.24 × 105 dm 3 mol−1 sec−1 and 2.75 × 108 sec−1, respectively, meaning net slow reactions because of low pre-exponential values caused by steric hindrance. ^

High performance shift invariant motion estimation and compensation in wavelet domain video compression

The contributions of this dissertation are in the development of two new interrelated approaches to video data compression: (1) A level-refined motion estimation and subband compensation method for the effective motion estimation and motion compensation. (2) A shift-invariant sub-decimation decomposition method in order to overcome the deficiency of the decimation process in estimating motion due to its shift-invariant property of wavelet transform. ^ The enormous data generated by digital videos call for an intense need of efficient video compression techniques to conserve storage space and minimize bandwidth utilization. The main idea of video compression is to reduce the interpixel redundancies inside and between the video frames by applying motion estimation and motion compensation (MEMO) in combination with spatial transform coding. To locate the global minimum of the matching criterion function reasonably, hierarchical motion estimation by coarse to fine resolution refinements using discrete wavelet transform is applied due to its intrinsic multiresolution and scalability natures. ^ Due to the fact that most of the energies are concentrated in the low resolution subbands while decreased in the high resolution subbands, a new approach called level-refined motion estimation and subband compensation (LRSC) method is proposed. It realizes the possible intrablocks in the subbands for lower entropy coding while keeping the low computational loads of motion estimation as the level-refined method, thus to achieve both temporal compression quality and computational simplicity. ^ Since circular convolution is applied in wavelet transform to obtain the decomposed subframes without coefficient expansion, symmetric-extended wavelet transform is designed on the finite length frame signals for more accurate motion estimation without discontinuous boundary distortions. ^ Although wavelet transformed coefficients still contain spatial domain information, motion estimation in wavelet domain is not as straightforward as in spatial domain due to the shift variance property of the decimation process of the wavelet transform. A new approach called sub-decimation decomposition method is proposed, which maintains the motion consistency between the original frame and the decomposed subframes, improving as a consequence the wavelet domain video compressions by shift invariant motion estimation and compensation. ^

Switching patterns and steady-state analysis of grid-connected and stand-alone single-stage boost-inverters for PV applications

Renewable or sustainable energy (SE) sources have attracted the attention of many countries because the power generated is environmentally friendly, and the sources are not subject to the instability of price and availability. This dissertation presents new trends in the DC-AC converters (inverters) used in renewable energy sources, particularly for photovoltaic (PV) energy systems. A review of the existing technologies is performed for both single-phase and three-phase systems, and the pros and cons of the best candidates are investigated. In many modern energy conversion systems, a DC voltage, which is provided from a SE source or energy storage device, must be boosted and converted to an AC voltage with a fixed amplitude and frequency. A novel switching pattern based on the concept of the conventional space-vector pulse-width-modulated (SVPWM) technique is developed for single-stage, boost-inverters using the topology of current source inverters (CSI). The six main switching states, and two zeros, with three switches conducting at any given instant in conventional SVPWM techniques are modified herein into three charging states and six discharging states with only two switches conducting at any given instant. The charging states are necessary in order to boost the DC input voltage. It is demonstrated that the CSI topology in conjunction with the developed switching pattern is capable of providing the required residential AC voltage from a low DC voltage of one PV panel at its rated power for both linear and nonlinear loads. In a micro-grid, the active and reactive power control and consequently voltage regulation is one of the main requirements. Therefore, the capability of the single-stage boost-inverter in controlling the active power and providing the reactive power is investigated. It is demonstrated that the injected active and reactive power can be independently controlled through two modulation indices introduced in the proposed switching algorithm. The system is capable of injecting a desirable level of reactive power, while the maximum power point tracking (MPPT) dictates the desirable active power. The developed switching pattern is experimentally verified through a laboratory scaled three-phase 200W boost-inverter for both grid-connected and stand-alone cases and the results are presented.

Prolegomenon to a History of Travel

The author attempts to provide a definition of travel by comparing it with the instinctive migration of animals and birds and viewing its changes over time. As a study of motion voluntarily undertaken, a history of travel can contribute to a better understanding of human beings

Joint-specific changes in locomotor complexity in the absence of muscle atrophy following incomplete spinal cord injury

ackground Following incomplete spinal cord injury (iSCI), descending drive is impaired, possibly leading to a decrease in the complexity of gait. To test the hypothesis that iSCI impairs gait coordination and decreases locomotor complexity, we collected 3D joint angle kinematics and muscle parameters of rats with a sham or an incomplete spinal cord injury. Methods 12 adult, female, Long-Evans rats, 6 sham and 6 mild-moderate T8 iSCI, were tested 4 weeks following injury. The Basso Beattie Bresnahan locomotor score was used to verify injury severity. Animals had reflective markers placed on the bony prominences of their limb joints and were filmed in 3D while walking on a treadmill. Joint angles and segment motion were analyzed quantitatively, and complexity of joint angle trajectory and overall gait were calculated using permutation entropy and principal component analysis, respectively. Following treadmill testing, the animals were euthanized and hindlimb muscles removed. Excised muscles were tested for mass, density, fiber length, pennation angle, and relaxed sarcomere length. Results Muscle parameters were similar between groups with no evidence of muscle atrophy. The animals showed overextension of the ankle, which was compensated for by a decreased range of motion at the knee. Left-right coordination was altered, leading to left and right knee movements that are entirely out of phase, with one joint moving while the other is stationary. Movement patterns remained symmetric. Permutation entropy measures indicated changes in complexity on a joint specific basis, with the largest changes at the ankle. No significant difference was seen using principal component analysis. Rats were able to achieve stable weight bearing locomotion at reasonable speeds on the treadmill despite these deficiencies. Conclusions Decrease in supraspinal control following iSCI causes a loss of complexity of ankle kinematics. This loss can be entirely due to loss of supraspinal control in the absence of muscle atrophy and may be quantified using permutation entropy. Joint-specific differences in kinematic complexity may be attributed to different sources of motor control. This work indicates the importance of the ankle for rehabilitation interventions following spinal cord injury.

Dynamic Behavior and Fatigue Life of Highway Bridges Due to Doubling Heavy Vehicles

An increase in the demand for the freight shipping in the United States has been predicted for the near future and Longer Combination Vehicles (LCVs), which can carry more loads in each trip, seem like a good solution for the problem. Currently, utilizing LCVs is not permitted in most states of the US and little research has been conducted on the effects of these heavy vehicles on the roads and bridges. In this research, efforts are made to study these effects by comparing the dynamic and fatigue effects of LCVs with more common trucks. Ten Steel and prestressed concrete bridges with span lengths ranging from 30’ to 140’ are designed and modeled using the grid system in MATLAB. Additionally, three more real bridges including two single span simply supported steel bridges and a three span continuous steel bridge are modeled using the same MATLAB code. The equations of motion of three LCVs as well as eight other trucks are derived and these vehicles are subjected to different road surface conditions and bumps on the roads and the designed and real bridges. By forming the bridge equations of motion using the mass, stiffness and damping matrices and considering the interaction between the truck and the bridge, the differential equations are solved using the ODE solver in MATLAB and the results of the forces in tires as well as the deflections and moments in the bridge members are obtained. The results of this study show that for most of the bridges, LCVs result in the smallest values of Dynamic Amplification Factor (DAF) whereas the Single Unit Trucks cause the highest values of DAF when traveling on the bridges. Also in most cases, the values of DAF are observed to be smaller than the 33% threshold suggested by the design code. Additionally, fatigue analysis of the bridges in this study confirms that by replacing the current truck traffic with higher capacity LCVs, in most cases, the remaining fatigue life of the bridge is only slightly decreased which means that taking advantage of these larger vehicles can be a viable option for decision makers.

Investigation of spatial patterns of ground-water exchange with lakes, using a three-dimensional numerical model

Hydrogeologic variables controlling groundwater exchange with inflow and flow-through lakes were simulated using a three-dimensional numerical model (MODFLOW) to investigate and quantify spatial patterns of lake bed seepage and hydraulic head distributions in the porous medium surrounding the lakes. Also, the total annual inflow and outflow were calculated as a percentage of lake volume for flow-through lake simulations. The general exponential decline of seepage rates with distance offshore was best demonstrated at lower anisotropy ratio (i.e., Kh/Kv = 1, 10), with increasing deviation from the exponential pattern as anisotropy was increased to 100 and 1000. 2-D vertical section models constructed for comparison with 3-D models showed that groundwater heads and seepages were higher in 3-D simulations. Addition of low conductivity lake sediments decreased seepage rates nearshore and increased seepage rates offshore in inflow lakes, and increased the area of groundwater inseepage on the beds of flow-through lakes. Introduction of heterogeneity into the medium decreased the water table and seepage ratesnearshore, and increased seepage rates offshore in inflow lakes. A laterally restricted aquifer located at the downgradient side of the flow-through lake increased the area of outseepage. Recharge rate, lake depth and lake bed slope had relatively little effect on the spatial patterns of seepage rates and groundwater exchange with lakes.

The status and ecology of the American alligator (Alligator mississippiensis) in Par Pond, Savannah River site

Par Pond is a man-made 1120 ha cooling reservoir located on the Savannah River Site near Aiken, South Carolina. From 1972-1978 a detailed study on the status of the alligator in Par Pond was conducted by Tom Murphy (unpub. MS thesis Univ. of GA, 1977). Murphy estimated that approximately 110 alligators inhabited Par Pond with an adult (> 1.8 m) to juvenile (< 1.8 m) ratio of (1.8:1), an overall sex ratio of 3.2:1, and an average of only 2.3 nests/yr. The purpose of this study (1986-1989) was to determine the current population size and structure, determine how the population has changed in the last 15 years and to examine growth and survival of juvenile alligators. Data were collected by monthly night-time eyeshine counts aerial surveys, capturing animals, and locating and following the fate of nests. There was a strong positive correlation between water temperature and the number of alligators observed during eyeshine counts. Both eyeshine counts and aerial surveys were highest in spring and varied seasonally. A total of 184 different non-hatchling and 157 hatchling alligators were captured between May 1986 and November 1988. Population estimates and size distributions based on capture data indicate that over the last 15 years the population has increased from approximately 110 to 200 alligators, and the size distribution has shifted from one dominated by large adults to one that has a higher proportion of juveniles. The current sex ratio (2.6:1) is not significantly different from that reported by Murphy (1977, 3.2:1). However, the average number of nests/yr has increased from 2.3 to 4.0. Data on juvenile growth and survival show that the growth rate of hatchlings (32.9 cm/yr total length) is greater than that of animals age 1-3 (21.6 cm/yr total length) and survival of all ages is variable between years and between clutches. Results from this study indicate that from 1972-988 the population has increased ac an average exponential rate of 6 % per year. If conditions in Par Pond do not change, the population size should continue to increase.

Aerodynamic Testing of Variable Message Signs

The increasing nationwide interest in intelligent transportation systems (ITS) and the need for more efficient transportation have led to the expanding use of variable message sign (VMS) technology. VMS panels are substantially heavier than flat panel aluminum signs and have a larger depth (dimension parallel to the direction of traffic). The additional weight and depth can have a significant effect on the aerodynamic forces and inertial loads transmitted to the support structure. The wind induced drag forces and the response of VMS structures is not well understood. Minimum design requirements for VMS structures are contained in the American Association of State Highway Transportation Officials Standard Specification for Structural Support for Highway Signs, Luminaires, and Traffic Signals (AASHTO Specification). However the Specification does not take into account the prismatic geometry of VMS and the complex interaction of the applied aerodynamic forces to the support structure. In view of the lack of code guidance and the limited number research performed so far, targeted experimentation and large scale testing was conducted at the Florida International University (FIU) Wall of Wind (WOW) to provide reliable drag coefficients and investigate the aerodynamic instability of VMS. A comprehensive range of VMS geometries was tested in turbulence representative of the high frequency end of the spectrum in a simulated suburban atmospheric boundary layer. The mean normal, lateral and vertical lift force coefficients, in addition to the twisting moment coefficient and eccentricity ratio, were determined using the measured data for each model. Wind tunnel testing confirmed that drag on a prismatic VMS is smaller than the 1.7 suggested value in the current AASHTO Specification (2013). An alternative to the AASHTO Specification code value is presented in the form of a design matrix. Testing and analysis also indicated that vortex shedding oscillations and galloping instability could be significant for VMS signs with a large depth ratio attached to a structure with a low natural frequency. The effect of corner modification was investigated by testing models with chamfered and rounded corners. Results demonstrated an additional decrease in the drag coefficient but a possible Reynolds number dependency for the rounded corner configuration.

Switching Patterns and Steady-State Analysis of Grid-Connected and Stand-Alone Single-Stage Boost-Inverters for PV Applications

Renewable or sustainable energy (SE) sources have attracted the attention of many countries because the power generated is environmentally friendly, and the sources are not subject to the instability of price and availability. This dissertation presents new trends in the DC-AC converters (inverters) used in renewable energy sources, particularly for photovoltaic (PV) energy systems. A review of the existing technologies is performed for both single-phase and three-phase systems, and the pros and cons of the best candidates are investigated. In many modern energy conversion systems, a DC voltage, which is provided from a SE source or energy storage device, must be boosted and converted to an AC voltage with a fixed amplitude and frequency. A novel switching pattern based on the concept of the conventional space-vector pulse-width-modulated (SVPWM) technique is developed for single-stage, boost-inverters using the topology of current source inverters (CSI). The six main switching states, and two zeros, with three switches conducting at any given instant in conventional SVPWM techniques are modified herein into three charging states and six discharging states with only two switches conducting at any given instant. The charging states are necessary in order to boost the DC input voltage. It is demonstrated that the CSI topology in conjunction with the developed switching pattern is capable of providing the required residential AC voltage from a low DC voltage of one PV panel at its rated power for both linear and nonlinear loads. In a micro-grid, the active and reactive power control and consequently voltage regulation is one of the main requirements. Therefore, the capability of the single-stage boost-inverter in controlling the active power and providing the reactive power is investigated. It is demonstrated that the injected active and reactive power can be independently controlled through two modulation indices introduced in the proposed switching algorithm. The system is capable of injecting a desirable level of reactive power, while the maximum power point tracking (MPPT) dictates the desirable active power. The developed switching pattern is experimentally verified through a laboratory scaled three-phase 200W boost-inverter for both grid-connected and stand-alone cases and the results are presented.