1000 resultados para TR alpha


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MCT2 is the major neuronal monocarboxylate transporter (MCT) that allows the supply of alternative energy substrates such as lactate to neurons. Recent evidence obtained by electron microscopy has demonstrated that MCT2, like alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, is localized in dendritic spines of glutamatergic synapses. Using immunofluorescence, we show in this study that MCT2 colocalizes extensively with GluR2/3 subunits of AMPA receptors in neurons from various mouse brain regions as well as in cultured neurons. It also colocalizes with GluR2/3-interacting proteins, such as C-kinase-interacting protein 1, glutamate receptor-interacting protein 1 and clathrin adaptor protein. Coimmunoprecipitation of MCT2 with GluR2/3 and C-kinase-interacting protein 1 suggests their close interaction within spines. Parallel changes in the localization of both MCT2 and GluR2/3 subunits at and beneath the plasma membrane upon various stimulation paradigms were unraveled using an original immunocytochemical and transfection approach combined with three-dimensional image reconstruction. Cell culture incubation with AMPA or insulin triggered a marked intracellular accumulation of both MCT2 and GluR2/3, whereas both tumor necrosis factor alpha and glycine (with glutamate) increased their cell surface immunolabeling. Similar results were obtained using Western blots performed on membrane or cytoplasm-enriched cell fractions. Finally, an enhanced lactate flux into neurons was demonstrated after MCT2 translocation on the cell surface. These observations provide unequivocal evidence that MCT2 is linked to AMPA receptor GluR2/3 subunits and undergoes a similar translocation process in neurons upon activation. MCT2 emerges as a novel component of the synaptic machinery putatively linking neuroenergetics to synaptic transmission.

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Mature T cells comprise two mutually exclusive lineages expressing heterodimeric alpha beta or gamma delta antigen receptors. During development, beta, gamma, and delta genes rearrange before alpha, and mature gamma delta cells arise in the thymus prior to alpha beta cells. The mechanism underlying commitment of immature T cells to the alpha beta or gamma delta lineage is controversial. Since the delta locus is located within the alpha locus, rearrangement of alpha genes leads to deletion of delta. We have examined the rearrangement status of the delta locus immediately prior to alpha rearrangement. We find that many thymic precursors of alpha beta cells undergo VDJ delta rearrangements. Furthermore, the same cells frequently coexpress sterile T early alpha (TEA) transcripts originating 3' of C delta and 5' of the most upstream J alpha, thus implying that individual alpha beta lineage cells undergo sequential VDJ delta and VJ alpha rearrangements. Finally, VDJ delta rearrangements in immature alpha beta cells appear to be random, supporting models in which alpha beta lineage commitment is determined independently of the rearrangement status at the TCR delta locus.

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Granular shoulders need to be maintained on a regular basis because edge ruts and potholes develop, posing a safety hazard to motorists. The successful mitigation of edge-rut issues for granular shoulders would increase safety and reduce the number of procedures currently required to maintain granular shoulders in Iowa. In addition, better performance of granular shoulders reduces the urgency to pave granular shoulders. Delaying or permanently avoiding paving shoulders where possible allows more flexibility in making investments in the road network. To stabilize shoulders and reduce the number of maintenance cycles necessary per season, one possible stabilizing agent—acidulated soybean oil soapstock—was investigated in this research. A pilot testing project was conducted for selected problematic shoulders in northern and northeastern Iowa. Soapstock was applied on granular shoulders and monitored during application and pre- and post-application. Application techniques were documented and the percentage of application success was calculated for each treated shoulder section. As a result of this research, it was concluded that soybean oil soapstock can be an effective stabilizer for granular shoulders under certain conditions. The researchers also developed draft specifications that could possibly be used to engage a contractor to perform the work using a maintenance-type construction contract. The documented application techniques from this project could be used as guidance for those who want to apply soapstock for stabilizing granular shoulders but might not be familiar with this technique.

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Anti-TNF alpha are immunomodulatory treatments prescribed for some rheumatologic inflammatory diseases (ex: spondylarthropathy, rheumatoid polyarthritis). The randomised studies suggested that anti-TNF alpha therapy is associated with an overall risk of infectious diseases. The results of the observational studies are more reassuring. In this article, we will describe some results of theses studies and propose some practical recommendations in use of the anti-TNF alpha therapy.

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Hydrologic analysis is a critical part of transportation design because it helps ensure that hydraulic structures are able to accommodate the flow regimes they are likely to see. This analysis is currently conducted using computer simulations of water flow patterns, and continuing developments in elevation survey techniques result in higher and higher resolution surveys. Current survey techniques now resolve many natural and anthropogenic features that were not practical to map and, thus, require new methods for dealing with depressions and flow discontinuities. A method for depressional analysis is proposed that uses the fact that most anthropogenically constructed embankments are roughly more symmetrical with greater slopes than natural depressions. An enforcement method for draining depressions is then analyzed on those depressions that should be drained. This procedure has been evaluated on a small watershed in central Iowa, Walnut Creek of the South Skunk River, HUC12 # 070801050901, and was found to accurately identify 88 of 92 drained depressions and place enforcements within two pixels, although the method often tries to drain prairie pothole depressions that are bisected by anthropogenic features.

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Red light running continues to be a serious safety concern for many communities in the United States. The Federal Highway Administration reported that in 2011, red light running accounted for 676 fatalities nationwide. Red light running crashes at a signalized intersections are more serious, especially in high speed corridors where speeds are above 35 mph. Many communities have invested in red light countermeasures including low-cost strategies (e.g. signal backplates, targeted enforcement, signal timing adjustments and improvement with signage) to high-cost strategies (e.g. automated enforcement and intersection geometric improvements). This research study investigated intersection confirmation lights as a low-cost strategy to reduce red light running violations. Two intersections in Altoona and Waterloo, Iowa were equipped with confirmation lights which targeted the through and left turning movements. Confirmation lights enable a single police officer to monitor a specific lane of traffic downstream of the intersection. A before-after analysis was conducted in which a change in red light running violations prior to- and 1 and 3 months after installation were evaluated. A test of proportions was used to determine if the change in red light running violation rates were statistically significant at the 90 and 95 percent levels of confidence. The two treatment intersections were then compared to the changes of red light running violation rates at spillover intersections (directly adjacent to the treatment intersections) and control intersections. The results of the analysis indicated a 10 percent reduction of red light running violations in Altoona and a 299 percent increase in Waterloo at the treatment locations. Finally, the research team investigated the time into red for each observed red light running violation. The analysis indicated that many of the violations occurred less than one second into the red phase and that most of the violation occurred during or shortly after the all-red phase.

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Blowing and drifting of snow is a major concern for transportation efficiency and road safety in regions where their development is common. One common way to mitigate snow drift on roadways is to install plastic snow fences. Correct design of snow fences is critical for road safety and maintaining the roads open during winter in the US Midwest and other states affected by large snow events during the winter season and to maintain costs related to accumulation of snow on the roads and repair of roads to minimum levels. Of critical importance for road safety is the protection against snow drifting in regions with narrow rights of way, where standard fences cannot be deployed at the recommended distance from the road. Designing snow fences requires sound engineering judgment and a thorough evaluation of the potential for snow blowing and drifting at the construction site. The evaluation includes site-specific design parameters typically obtained with semi-empirical relations characterizing the local transport conditions. Among the critical parameters involved in fence design and assessment of their post-construction efficiency is the quantification of the snow accumulation at fence sites. The present study proposes a joint experimental and numerical approach to monitor snow deposits around snow fences, quantitatively estimate snow deposits in the field, asses the efficiency and improve the design of snow fences. Snow deposit profiles were mapped using GPS based real-time kinematic surveys (RTK) conducted at the monitored field site during and after snow storms. The monitored site allowed testing different snow fence designs under close to identical conditions over four winter seasons. The study also discusses the detailed monitoring system and analysis of weather forecast and meteorological conditions at the monitored sites. A main goal of the present study was to assess the performance of lightweight plastic snow fences with a lower porosity than the typical 50% porosity used in standard designs of such fences. The field data collected during the first winter was used to identify the best design for snow fences with a porosity of 50%. Flow fields obtained from numerical simulations showed that the fence design that worked the best during the first winter induced the formation of an elongated area of small velocity magnitude close to the ground. This information was used to identify other candidates for optimum design of fences with a lower porosity. Two of the designs with a fence porosity of 30% that were found to perform well based on results of numerical simulations were tested in the field during the second winter along with the best performing design for fences with a porosity of 50%. Field data showed that the length of the snow deposit away from the fence was reduced by about 30% for the two proposed lower-porosity (30%) fence designs compared to the best design identified for fences with a porosity of 50%. Moreover, one of the lower-porosity designs tested in the field showed no significant snow deposition within the bottom gap region beneath the fence. Thus, a major outcome of this study is to recommend using plastic snow fences with a porosity of 30%. It is expected that this lower-porosity design will continue to work well for even more severe snow events or for successive snow events occurring during the same winter. The approach advocated in the present study allowed making general recommendations for optimizing the design of lower-porosity plastic snow fences. This approach can be extended to improve the design of other types of snow fences. Some preliminary work for living snow fences is also discussed. Another major contribution of this study is to propose, develop protocols and test a novel technique based on close range photogrammetry (CRP) to quantify the snow deposits trapped snow fences. As image data can be acquired continuously, the time evolution of the volume of snow retained by a snow fence during a storm or during a whole winter season can, in principle, be obtained. Moreover, CRP is a non-intrusive method that eliminates the need to perform man-made measurements during the storms, which are difficult and sometimes dangerous to perform. Presently, there is lots of empiricism in the design of snow fences due to lack of data on fence storage capacity on how snow deposits change with the fence design and snow storm characteristics and in the estimation of the main parameters used by the state DOTs to design snow fences at a given site. The availability of such information from CRP measurements should provide critical data for the evaluation of the performance of a certain snow fence design that is tested by the IDOT. As part of the present study, the novel CRP method is tested at several sites. The present study also discusses some attempts and preliminary work to determine the snow relocation coefficient which is one of the main variables that has to be estimated by IDOT engineers when using the standard snow fence design software (Snow Drift Profiler, Tabler, 2006). Our analysis showed that standard empirical formulas did not produce reasonable values when applied at the Iowa test sites monitored as part of the present study and that simple methods to estimate this variable are not reliable. The present study makes recommendations for the development of a new methodology based on Large Scale Particle Image Velocimetry that can directly measure the snow drift fluxes and the amount of snow relocated by the fence.

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To conserve natural resources and energy, the amount of recycled asphalt pavement has been steadily increasing in the construction of asphalt pavements. The objective of this study is to develop quality standards for inclusion of high RAP content. To determine if the higher percentage of RAP materials can be used on Iowa’s state highways, three test sections with target amounts of RAP materials of 30%, 35% and 40% by weight were constructed on Highway 6 in Iowa City. To meet Superpave mix design requirements for mixtures with high RAP contents, it was necessary to fractionate the RAP materials. Three test sections with actual RAP materials of 30.0%, 35.5% and 39.2% by weight were constructed and the average field densities from the cores were measured as 95.3%, 94.0%, and 94.3%, respectively. Field mixtures were compacted in the laboratory to evaluate moisture sensitivity using a Hamburg Wheel Tracking Device. After 20,000 passes, rut depths were less than 3mm for mixtures obtained from three test sections. The binder was extracted from the field mixtures from each test section and tested to identify the effects of RAP materials on the performance grade of the virgin binder. Based on Dynamic Shear Rheometer and Bending Beam Rheometer tests, the virgin binders (PG 64-28) from test sections with 30.0%, 35.5% and 39.2% RAP materials were stiffened to PG 76-22, PG 76-16, and PG 82-16, respectively. The Semi-Circular Bending (SCB) test was performed on laboratory compacted field mixtures with RAP amounts of 30.0%, 35.5% and 39.2% at two different temperatures of -18 and -30 °C. As the test temperature decreased, the fracture energy decreased and the stiffness increased. As the RAP amount increased, the stiffness increased and the fracture energy decreased. Finally, a condition survey of the test sections was conducted to evaluate their short-term pavement performance and the reflective transverse cracking did not increase as RAP amount was increased from 30.0% to 39.2%.

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Asphalt pavements suffer various failures due to insufficient quality within their design lives. The American Association of State Highway and Transportation Officials (AASHTO) Mechanistic-Empirical Pavement Design Guide (MEPDG) has been proposed to improve pavement quality through quantitative performance prediction. Evaluation of the actual performance (quality) of pavements requires in situ nondestructive testing (NDT) techniques that can accurately measure the most critical, objective, and sensitive properties of pavement systems. The purpose of this study is to assess existing as well as promising new NDT technologies for quality control/quality assurance (QC/QA) of asphalt mixtures. Specifically, this study examined field measurements of density via the PaveTracker electromagnetic gage, shear-wave velocity via surface-wave testing methods, and dynamic stiffness via the Humboldt GeoGauge for five representative paving projects covering a range of mixes and traffic loads. The in situ tests were compared against laboratory measurements of core density and dynamic modulus. The in situ PaveTracker density had a low correlation with laboratory density and was not sensitive to variations in temperature or asphalt mix type. The in situ shear-wave velocity measured by surface-wave methods was most sensitive to variations in temperature and asphalt mix type. The in situ density and in situ shear-wave velocity were combined to calculate an in situ dynamic modulus, which is a performance-based quality measurement. The in situ GeoGauge stiffness measured on hot asphalt mixtures several hours after paving had a high correlation with the in situ dynamic modulus and the laboratory density, whereas the stiffness measurement of asphalt mixtures cooled with dry ice or at ambient temperature one or more days after paving had a very low correlation with the other measurements. To transform the in situ moduli from surface-wave testing into quantitative quality measurements, a QC/QA procedure was developed to first correct the in situ moduli measured at different field temperatures to the moduli at a common reference temperature based on master curves from laboratory dynamic modulus tests. The corrected in situ moduli can then be compared against the design moduli for an assessment of the actual pavement performance. A preliminary study of microelectromechanical systems- (MEMS)-based sensors for QC/QA and health monitoring of asphalt pavements was also performed.

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Single-vehicle run-off-road crashes are the most common crash type on rural two-lane Iowa roads. Rumble strips have been proven effective in mitigating these crashes, but these strips are commonly installed in paved shoulders adjacent to higher-volume roads owned by the State of Iowa. Lower-volume paved rural roads owned by local agencies do not commonly feature paved shoulders but frequently experience run-off-road crashes. This project involved installing “rumble stripes,” which are a combination of conventional rumble strips with a painted edge line placed on the surface of the milled area, along the edge of the travel lanes but at a narrow width to avoid possible intrusion into the normal vehicle travel paths. Candidate locations were selected from a list of paved local rural roads that were most recently listed in the top 5% of roads for run-off-road crashes in Iowa. Horizontal curves were the most favored locations for rumble stripe installation because they commonly experience roadway departure crashes. The research described in this report was part of a project funded by the Federal Highway Administration, Iowa Highway Research Board, and Iowa Department of Transportation to evaluate the effectiveness of edge line rumble strips in Iowa. The project evaluated the effectiveness of “rumble stripes” in reducing run-off-road crashes and in improving the longevity and wet weather visibility of edge line markings. This project consists of two phases. The first phase was to select pilot study locations, select a set of test sites, install rumble stripes, summarize lessons learned during installation, and provide a preliminary assessment of the rumble stripes’ performance. This information is summarized in this report. The purpose of the second phase is to provide a more long-term assessment of the performance of the pavement markings, conduct preliminary crash assessments, and evaluate lane keeping. This will result in a forthcoming second report.

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The relative occurrence of genetic variants of human alpha 1-acid glycoprotein (AGP) in relation to changes in glycosylation was studied in sera of patients with burn injury, media of cytokine-treated primary cultures of human hepatocytes and Hep 3B cells, and sera of transgenic mice expressing the human AGP-A gene. It is concluded (i) that the glycosylation of AGP was not dependent on its genetic expression and (ii) that both the variants determined by the AGP-A gene as well as by the AGP-B/B' genes are increased after inflammation or treatment with interleukins 1 and 6.

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A hallmark of aging is the sensorimotor deficit, characterized by an increased reaction time and a reduction of motor abilities. Some mechanisms such as motor inhibition deteriorate with aging because of neuronal density alterations and modifications of connections between brain regions. These deficits may be compensated throughout a recruitment of additional areas. Studies have shown that old adults have increased difficulty in performing bimanual coordination tasks compared with young adults. In contrast, motor switching is poorly documented and is expected to engage increasing resources in the elderly. The present study examines performances and electro-cortical correlates of motor switching in young and elderly adults.

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Conventional concrete is typically cured using external methods. External curing prevents drying of the surface, allows the mixture to stay warm and moist, and results in continued cement hydration (Taylor 2014). Internal curing is a relatively recent technique that has been developed to prolong cement hydration by providing internal water reservoirs in a concrete mixture that do not adversely affect the concrete mixture’s fresh or hardened physical properties. Internal curing grew out of the need for more durable structural concretes that were resistant to shrinkage cracking. Joint spacing for concrete overlays can be increased if slab warping is reduced or eliminated. One of the most promising potential benefits from using internal curing for concrete overlays, then, is the reduced number of joints due to increased joint spacing (Wei and Hansen 2008).

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Well-performing subsurface drainage systems form an important aspect of pavement design by the Iowa Department of Transportation (DOT). The recently completed Iowa Highway Research Board (IHRB) project TR-643 provided extensive insights into Iowa subsurface drainage practices and pavement subdrain outlet performance. However, the project TR-643 (Phase I) forensic testing and evaluation were carried out in a drought year and during the fall season in 2012. Based on the findings of IHRB Project TR-643, the Iowa DOT requested an expanded Phase II study to address several additional research needs: evaluate the seasonal variation effects (dry fall 2012 versus wet spring/summer 2013, etc.) on subdrain outlet condition and performance; investigate the characteristics of tufa formation in Iowa subdrain outlets; investigate the condition of composite pavement subdrain outlets; examine the effect of resurfacing/widening/rehabilitation on subdrain outlets (e.g., the effects of patching on subdrain outlet performance); and identify a suitable drain outlet protection mechanism (like a headwall) and design for Iowa subdrain outlets based on a review of practices adopted by nearby states. A detailed forensic test plan was developed and executed for inspecting the Iowa pavement subdrains in pursuit of fulfilling the Phase II study objectives. The observed outlets with blockage and the associated surface distresses in newly constructed jointed plain concrete pavements (JPCPs) were slightly higher during summer 2013 compared to fall 2012. However, these differences are not significant. Less tufa formation due to the recycled portland cement concrete (RPCC) base was observed with (a) the use of plastic outlet pipe without the gate screen–type rodent guard and (b) the use of blended RPCC and virgin aggregate materials. In hot-mix asphalt (HMA) over JPCP, moisture-related distress types (e.g., reflection cracking) were observed more near blocked drainage outlet locations than near “no blockage” outlet locations. This finding indicates that compromised drainage outlet performance could accelerate the development of moisture-related distresses in Iowa composite pavement systems. ****** Note: This report follows on work report in "Evaluating Roadway Subsurface Drainage Practices, 2013" http://publications.iowa.gov/14902/ Note: This record contains links to the 210 page full report as well as the 3 page tech transfer summary. The summary is NOT deposited separately.