Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis.

We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS. Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.

Phototropism: Translating light into directional growth.

Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.

Investigation of Two Bridge Alternatives for Low Volume Roads, Volume 1 of 2 Concept 1: Precast Steel Beam Units, HR-382, 1997

Recent reports have indicated that 23.5% of the nation's highway bridges are structurally deficient and 17.7% are functionally obsolete. A significant number of these bridges are on the Iowa secondary road system where over 86% of the rural bridge management responsibilities are assigned to the counties. Some of the bridges can be strengthened or otherwise rehabilitated, but many more are in need of immediate replacement. In a recent investigation (HR-365 "Evaluation of Bridge Replacement Alternatives for the County Bridge System") several types of replacement bridges that are currently being used on low volume roads were identified. It was also determined that a large number of counties (69%) have the ability and are interested in utilizing their own forces to design and construct short span bridges. In reviewing the results from HR-365, the research team developed one "new" bridge replacement concept and a modification of a replacement system currently being used. Both of these bridge replacement alternatives were investigated in this study, the results of which are presented in two volumes. This volume (Volume 1) presents the results of Concept 1 - Steel Beam Precast Units. Concept 2 - Modification of the Beam-in-Slab Bridge is presented in Volume 2. Concept 1, involves the fabrication of precast units (two steel beams connected by a concrete slab) by county work forces. Deck thickness is limited so that the units can be fabricated at one site and then transported to the bridge site where they are connected and the remaining portion of the deck placed. Since Concept 1 bridge is primarily intended for use on low-volume roads, the precast units can be constructed with new or used beams. In the experimental part of the investigation, there were three types of static load tests: small scale connector tests, "handling strength" tests, and service and overload tests of a model bridge. Three finite element models for analyzing the bridge in various states of construction were also developed. Small scale connector tests were completed to determine the best method of connecting the precast double-T (PCDT) units. "Handling strength" tests on an individual PCDT unit were performed to determine the strength and behavior of the precast unit in this configuration. The majority of the testing was completed on the model bridge [L=9,750 mm (32 ft), W=6,400 mm (21 ft)] which was fabricated using the precast units developed. Some of the variables investigated in the model bridge tests were number of connectors required to connect adjacent precast units, contribution of diaphragms to load distribution, influence of position of diaphragms on bridge strength and load distribution, and effect of cast-in-place portion of deck on load distribution. In addition to the service load tests, the bridge was also subjected to overload conditions. Using the finite element models developed, one can predict the behavior and strength of bridges similar to the laboratory model as well as design them. Concept 1 has successfully passed all laboratory testing; the next step is to field test it.

Investigation of Two Bridge Alternatives for Low Volume Roads - Phase II Volume 1 of 2 Concept 1: Steel Beam Precast Units, TR-410, 2000

This project continues the research which addresses the numerous bridge problems on the Iowa secondary road system. It is a continuation (Phase 2) of Project HR-382, in which two replacement alternatives (Concept 1: Steel Beam Precast Units and Concept 2: Modification of the Benton County Beam-in-Slab Bridge) were investigated. In previous research for concept 1, a precast unit bridge was developed through laboratory testing. The steel-beam precast unit bridge requires the fabrication of precast double-tee (PCDT) units, each consisting of two steel beams connected by a reinforced concrete deck. The weight of each PCDT unit is minimized by limiting the deck thickness to 4 in., which permits the units to be constructed off-site and then transported to the bridge site. The number of units required is a function of the width of bridge desired. Once the PCDT units are connected, a cast-in-place reinforced concrete deck is cast over the PCDT units and the bridge railing attached. Since the steel beam PCDT unit bridge design is intended primarily for use on low-volume roads, used steel beams can be utilized for a significant cost savings. In previous research for concept 2, an alternate shear connector (ASC) was developed and subjected to static loading. In this investigation, the ASC was subjected to cyclic loading in both pushout specimens and composite beam tests. Based on these tests, the fatigue strength of the ASC was determined to be significantly greater than that required in typical low volume road single span bridges. Based upon the construction and service load testing, the steel-beam precast unit bridge was successfully shown to be a viable low volume road bridge alternative. The construction process utilized standard methods resulting in a simple system that can be completed with a limited staff. Results from the service load tests indicated adequate strength for all legal loads. An inspection of the bridge one year after its construction revealed no change in the bridge's performance. Each of the systems previously described are relatively easy to construct. Use of the ASC rather than the welded studs significantly simplified the work, equipment, and materials required to develop composite action between the steel beams and the concrete deck.

Crystallization and properties of poly(ethylene terephtalate) copolymers containing 5-tert-butyl isophtalic units

The influence of incorporating 5-tert-butyl isophthalic units (tBI) in the polymer chain of poly(ethylene terephthalate) (PET) on the crystallization behavior, crystal structure, and tensile and gas transport properties of this polyester was evaluated. Random poly(ethyleneterephthalate-co-5-tert-butyl isophthalate) copolyesters (PETtBI) containing between 5 and 40 mol% of tBI units were examined. Isothermal crystallization studies were performed on amorphous glassy films at 120 8C and on molten samples at 200 8C by means of differential scanning calorimetry. Furthermore, the non-isothermal crystallization behavior of the copolyesters was investigated. It was observed that both crystallinity and crystallization rate of the PETtBI copolyesters tend to decrease largely with the comonomeric content, except for the copolymer containing 5 mol% of tBI units, which crystallized faster than PET. Fiber X-ray diffraction patterns of the semicrystalline PETtBI copolyesters proved that they adopt the same triclinic crystal structure as PET with the comonomeric units being excluded from the crystalline phase. Although PETtBI copolyesters became brittle for higher contents in tBI, the tensile modulus and strength of PET were barely affected by copolymerization. The ncorporation of tBI units slightly increased the permeability of PET, but copolymers containing up to 20 mol% of the comonomeric units were still able to present barrier properties.

Audit report of the State University of Iowa, Iowa City, Iowa, (University of Iowa) and its discretely presented component units as of and for the years ended June 30, 2013 and 2012

Audit report of the State University of Iowa, Iowa City, Iowa, (University of Iowa) and its discretely presented component units as of and for the years ended June 30, 2013 and 2012

Light intensity modulates the regulatory network of the shade avoidance response in Arabidopsis.

Plants such as Arabidopsis thaliana respond to foliar shade and neighbors who may become competitors for light resources by elongation growth to secure access to unfiltered sunlight. Challenges faced during this shade avoidance response (SAR) are different under a light-absorbing canopy and during neighbor detection where light remains abundant. In both situations, elongation growth depends on auxin and transcription factors of the phytochrome interacting factor (PIF) class. Using a computational modeling approach to study the SAR regulatory network, we identify and experimentally validate a previously unidentified role for long hypocotyl in far red 1, a negative regulator of the PIFs. Moreover, we find that during neighbor detection, growth is promoted primarily by the production of auxin. In contrast, in true shade, the system operates with less auxin but with an increased sensitivity to the hormonal signal. Our data suggest that this latter signal is less robust, which may reflect a cost-to-robustness tradeoff, a system trait long recognized by engineers and forming the basis of information theory.

Different colors of light lead to different adaptation and activation as determined by high-density EEG.

Light adaptation is crucial for coping with the varying levels of ambient light. Using high-density electroencephalography (EEG), we investigated how adaptation to light of different colors affects brain responsiveness. In a within-subject design, sixteen young participants were adapted first to dim white light and then to blue, green, red, or white bright light (one color per session in a randomized order). Immediately after both dim and bright light adaptation, we presented brief light pulses and recorded event-related potentials (ERPs). We analyzed ERP response strengths and brain topographies and determined the underlying sources using electrical source imaging. Between 150 and 261ms after stimulus onset, the global field power (GFP) was higher after dim than bright light adaptation. This effect was most pronounced with red light and localized in the frontal lobe, the fusiform gyrus, the occipital lobe and the cerebellum. After bright light adaptation, within the first 100ms after light onset, stronger responses were found than after dim light adaptation for all colors except for red light. Differences between conditions were localized in the frontal lobe, the cingulate gyrus, and the cerebellum. These results indicate that very short-term EEG brain responses are influenced by prior light adaptation and the spectral quality of the light stimulus. We show that the early EEG responses are differently affected by adaptation to different colors of light which may contribute to known differences in performance and reaction times in cognitive tests.

Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability.

Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.

Metric Training for the Transportation Industry Module I - Basic Introduction to the Use of International Units of Measure, HR-376

"Metric Training For The Highway Industry", HR-376 was designed to produce training materials for the various divisions of the Iowa DOT, local government and the highway construction industry. The project materials were to be used to introduce the highway industry in Iowa to metric measurements in their daily activities. Five modules were developed and used in training over 1,000 DOT, county, city, consultant and contractor staff in the use of metric measurements. The training modules developed deal with the planning through operation areas of highway transportation. The materials and selection of modules were developed with the aid of an advisory personnel from the highway industry. Each module is design as a four hour block of instruction and a stand along module for specific types of personnel. Each module is subdivided into four chapters with chapter one and four covering general topics common to all subjects. Chapters two and three are aimed at hands on experience for a specific group and subject. This module includes: Module 1 - Basic Introduction to the Use of International Units of Measurement. This module is designed for use by all levels of personnel, primarily office staff, and provides a basic background in the use of metric measurements in both written and oral communications.

Blanket Curing to Promote Early Strength Concrete, MLR-87-7, 1989

Fast Track concrete has proven to be successful in obtaining high early strengths. This benefit does not come without cost. Special Type III cement and insulating blankets to accelerate the cure add to its expense when compared to conventional paving. This research was intended to determine the benefit derived from the use of insulating blankets to accelerate strength gain in three concrete mixes using Type I cement. The goal was to determine mixes and curing procedures that would result in a range of opening times. This determination would allow the most economical design for a particular project by tailoring it to a specific time restraint. Three mixes of various cement content were tested in the field. Flexural beams were cast for each mix and tested at various ages. Two test sections were placed for each mix, one section being cured with the addition of insulating blankets and the other being cured with only conventional curing compound. Iowa Department of Transportation specifications require 500 psi flexural strength before a pavement can be opened to traffic. Concrete with Fast Track proportions (nominal 7 1/2 bag), Type I cement, and insulating blankets reached that strength in approximately 36 hr, a standard mix (nominal 6 1/2 bag) using the blankets in approximately 48 hr, and the Fast Track proportions with Type I cement without blankets in about 60 hr. The results showed a significant improvement in early strength gain with the use of insulating blankets.

Investigation of the Loss of Prestress in Prestressed Concrete Beams due to Steam Curing, HR-62, 1961

Mass production of prestressed concrete beams is facilitated by the accelerated curing of the concrete. The ·method most commonly used for this purpose is steam curing at atmospheric pressure. This requires concrete temperatures as high as 150°F. during the curing period. Prestressing facilities in Iowa are located out of doors. This means that during the winter season the forms are set and the steel cables are stressed at temperatures as low as 0°F. The thermal expansion of the prestressing cables should result in a reduction of the stress which was placed in them at the lower temperature. If the stress is reduced in the cables, then the amount of prestress ultimately transferred to the concrete may be less than the amount for which the beam was designed. Research project HR-62 was undertaken to measure and explain the difference between the initial stress placed in the cables and the actual stress which is eventually transferred to the concrete. The project was assigned to the Materials Department Laboratory under the general supervision of the Testing Engineer, Mr. James W. Johnson. A small stress bed complete with steam curing facilities was set up in the laboratory, and prestressed concrete beams were fabricated under closely controlled conditions. Measurements were made to determine the initial stress in the steel and the final stress in the concrete. The results of these tests indicate that there is a general loss of prestressing force in excess of that caused by elastic shortening of the concrete. The exact amount of the loss and the identification of the factors involved could not be determined from this limited investigation.

Effect of Grooved Concrete on Curing Efficiency, MLR-83-4, 1983

The textured concrete surface on all PCC primary paving projects (and when specified on secondary projects) is required to be grooved in a specified manner. The laboratory test for determining the efficiency index of concrete curing compounds is made on slabs that are not grooved. This short investigation was undertaken to determine any changes in the curing efficiency index when using various rates of application of curing compound on grooved concrete. Currently a 95 percent curing efficiency index is specified at an application rate of 15 square yards per gallon. Can this efficiency be achieved, and if so at what application rate, on grooved concrete? Grooving the concrete greatly increases the surface area and also causes the liquid curing compound to run off the high spots and collect in the grooves.

Durability of P.C. Concrete as Affected by Aggregate Size, Curing and Proportions, R-214, 1968

The durability of concrete is a most important aspect in pavement life. Deterioration of the interstate portland cement concrete pavement has prompted various studies of factors which may contribute to the durability. Studies of cores taken from deteriorated areas indicated that the larger particles of coarse aggregate may contribute greatly to the problem. This indication was mainly due to the analysis of the cracking pattern which showed that most of the cracks passed through the larger aggregates and the larger aggregate particles were more cracked than the smaller particles. The purpose of this project is to determine if the size of the coarse aggregate has a bearing on the durability of freeze and thaw beams. A secondary purpose of this project is to determine what effect the method of curing and proportions have on the durability of freeze and thaw beams.