Selective resonance suppression 1H-[13C] NMR spectroscopy with asymmetric adiabatic RF pulses.

Despite obvious improvements in spectral resolution at high magnetic field, the detection of 13C labeling by 1H-[13C] NMR spectroscopy remains hampered by spectral overlap, such as in the spectral region of 1H resonances bound to C3 of glutamate (Glu) and glutamine (Gln), and C6 of N-acetylaspartate (NAA). The aim of this study was to develop, implement, and apply a novel 1H-[13C] NMR spectroscopic editing scheme, dubbed "selective Resonance suppression by Adiabatic Carbon Editing and Decoupling single-voxel STimulated Echo Acquisition Mode" (RACED-STEAM). The sequence is based on the application of two asymmetric narrow-transition-band adiabatic RF inversion pulses at the resonance frequency of the 13C coupled to the protons that need to be suppressed during the mixing time (TM) period, alternating the inversion band downfield and upfield from the 13C resonance on odd and even scans, respectively, thus suppressing the detection of 1H resonances bound to 13C within the transition band of the inversion pulse. The results demonstrate the efficient suppression of 1H resonances bound to C3 of Glu and Gln, and C4 of Glu, which allows the 1H resonances bound to C6 of NAA and C4 of Gln to be revealed. The measured time course of the resolved labeling into NAA C6 with the new scheme was consistent with the slow turnover of NAA.

Estudi del procés de neurodegeneració

Les anomenades malalties neurodegeneratives tenen una simptomatologia i unes manifestacions clíniques molt diferents entre elles. No obstant, totes elles convergeixen en el mateix procés final, la neurodegeneració, que es manifestarà en diferents localitzacions o tipus cel·lulars del sistema nerviós. Nosaltres, plantegem la hipòtesi de que els processos moleculars i cel·lulars subjacents a la neurodegeneració són comuns per totes elles. Després de dur a terme un procés de selecció, es decideix treballar amb la malaltia de Parkinson, la d’Alzheimer, l’Esclerosi lateral amiotròfica i l’esclerosi múltiple. Hem pogut determinar que hi ha set processos moleculars o cel·lulars que estan associats al procés de neurodegeneració i que són comuns a totes elles. Havent-les estudiat per separat s’observa que el procés de neurodegeneració consisteix en una fallada en cadena de diferents sistemes moleculars i cel·lulars que tenen com a punt d’origen l’estrès oxidatiu. A aquest estrès s’hi pot arribar de diferents maneres. Una d’elles és l’exposició excessiva a certs metalls, que provoca la pèrdua dels sistemes antioxidants cel·lulars. Degut a això, els mitocondris reben un impacte oxidatiu massa gran i comencen a fallar. El fet que aquest orgànul actuï com a tampó del calci intracel·lular en provoca la seva desregulació, alterant d’aquesta manera el senyal nerviós. En resposta a l’estrès oxidatiu i tèrmic que genera la disfunció mitocondrial, s’activen les Proteïnes de Xoc Tèrmic (HSP) que actuant de citocines i presentadores d’antígens, inicien la resposta immunològica contra les cèl·lules danyades. Paral·lelament, s’observa un increment de la permeabilitat de la barrera hematoencefàlica degut a la pèrdua de les adhesions cel·lulars estretes per l’alta presència d’espècies reactives. Com a conseqüència de l’afebliment o el trencament de la barrera hematoencefàlica, es pot produir una entrada al SNC de diferents substàncies neurotòxiques i de cèl·lules del sistema immunitàri que, en condicions normals tenen l’accés restringit. Juntament amb aquestes cèl·lules immunològiques, també s’activen les cèl·lules del sistema immunitari innat residents al cervell, la micròglia, i totes elles secreten citocines proinflamatòries que contribueixen al procés de neurodegeneració. Nosaltres presentem els mecanismes pels quals aquesta inflamació, lluny d’atenuar-se, es cronifica per l’acció de certs bucles de retroalimentació positiva. Les diferents peculiaritats de cada malaltia contribueixen en aquest procés de diferents maneres, com és el cas dels pèptids β-amilides en la malaltia d’Alzheimer, l’α-sinucleina en el Parkinson, la superòxid dismutasa (SOD) en l’esclerosi lateral amiotròfica, o l’infiltració de leucòcits al cervell degut a la resposta autoimmune de l’esclerosi múltiple.Deixant de banda aquestes diferències, si el procés és comú entre totes elles, l’estudi a fons d’aquest procés hauria de poder permetre identificar dianes tarapèutiques que siguin comunes per les quatre malalties.

Systèmes de délivrance des médicaments pour le segment antérieur: bases fondamentales et applications cliniques [Drug delivery systems to target the anterior segment of the eye: fundamental bases and clinical applications].

The development of new drug delivery systems to target the anterior segment of the eye may offer many advantages: to increase the biodisponibility of the drug, to allow the penetration of drug that cannot be formulated as solutions, to obtain constant and sustained drug release, to achieve higher local concentrations without systemic effects, to target more specifically one tissue or cell type, to reduce the frequency of instillation and therefore increase the observance and comfort of the patient while reducing side effects of frequent instillation. Several approaches are developed, aiming to increase the corneal contact time by modified formulation or reservoir systems, or by increasing the tissue permeability using iontophoresis. To date, no ocular drug delivery system is ideal for all purposes. To maximize treatment efficacy, careful evaluation of the specific pathological condition, the targeted Intraocular tissue and the location of the most severe pathology must be made before selecting the method of delivery most suitable for each individual patient.

Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity.

Overactivation of the sympatho-adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of critical illnesses. In the same way, the administration of exogenous catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial oxygen supply/demand imbalance induced by the sustained activation of adrenergic receptors, catecholamines can damage cardiomyocytes by fostering mitochondrial dysfunction, via two main mechanisms. The first one is calcium overload, consecutive to β-adrenergic receptor-mediated activation of protein kinase A and subsequent phosphorylation of multiple Ca(2+)-cycling proteins. The second one is oxidative stress, primarily related to the transformation of catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of oxygen-derived free radicals. In turn, calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and mitochondrial dysfunction, have been reported with the use of cocaine, a common recreational drug with potent sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of catecholamine and cocaine-induced cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.

Haemodynamic role of vasopressin released during Finnish sauna.

The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P less than 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 +/- 0.2 pg/ml, P less than 0.01 mean +/- SEM) than before the sauna (1.0 +/- 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr(Me)AVP (5 micrograms/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.

Thin Asphalt Concrete Pavement on Crushed Rock Base, HR-2075, 2001

The road paving cost continues to increase and the backlog of projects waiting for funding is growing. Finding a more cost-effective way to use the available money to pave roads will result in more miles of road being paved with the same amount of money. This project is in Cass County on G35 between US 71 and Norway-Center. It consists of a thin layer of asphalt over a base designed to achieve stability while having some permeability. This project was paved in 1996. An asphalt cement concrete pavement was chosen for the project based on cost, convenience, and historic portland cement concrete problems in Cass County. The new pavement gives quicker access time to farms and residences.

Investigation of High Performance Concrete Pavement, MLR-05-01, 2006

The Iowa DOT has been using blended cements in ternary mixes since 1999. Use of these supplementary cementitious materials gives concrete with higher strengths and much lower permeability. Use of these materials has been incorporated for use in High Performance Concrete (HPC) decks to achieve lower permeability and thus long term performance. Since we have been using these materials in paving, it would be informative to determine what concrete pavement properties are enhanced as related to high performance concrete. The air void system was excellent at a spacing factor of 0.0047 in (0.120 mm). AVA spacing factor results are much higher than the hardened air void analysis. Although only 3 samples were tested between the image analysis air content and the RapidAir457, there is pretty good agreement between those test methods. Air void analysis indicates that excessive vibration was not required to place the concrete. Vibration was well within the specification limits with an average of 6683 vpm’s with a standard deviation of 461. Overall ride of the project was very good. The average smoothness for the project was 2.1 in/mile (33.8 mm/km). The International Roughness Index (IRI) was 81 in/mi (1.29 m/km). The compressive strength was 6260 psi (43.2 MPa) at 28 days and 6830 (47.1 MPa) at 56 days. The modulus of rupture by third point loading (MOR-TPL) tested at 28 days was 660 psi (4.55 MPa). The AASHTO T277 rapid chloride permeability results at 28 days using the Virginia cure method correlate fairly well with the 56 and 90 day results with standard curing. The Virginia cure method 28 day results were 2475 coulombs and the standard cure 56 and 90 day test results were 2180 and 2118, respectively.

Evaluation of Metakaolin for HPC Deck Overlays, MLR-11-01, 2011

The use of High Performance Concrete (HPC) in Iowa has consisted of achieving slightly higher compressive strengths with an emphasis on reduced permeability. Concrete with reduced permeability has increased durability by slowing moisture and chloride ingress. Achieving reduced permeability has typically been accomplished with combinations of slag and Class C fly ash, or the use of blended cements such as locally available Type IS(20), IS(25) and Type IP(25) in conjunction with Class C fly ash. Fly ash has been used in the majority of concrete placed in Iowa since 1984 and slag has been available in Iowa since 1995. During the economic downturn in 2008, one of the cement plants that produced a Type IS(25) cement was forced to shut down, which reduced the availability of blended cements, typically used on HPC deck overlays. Recently, a source of high reactivity metakaolin has been made available. Metakaolin is produced by heating a pure kaolinite clay to 650 to 700 °C in a rotary kiln (calcining). Metakaolin is a white pozzolan that is used to produce concrete with increased strengths, reduced permeability, reduced efflorescence, and resistance to alkali silica reactivity. The W.R. Grace MK-100 metakaolin will likely be available in dissolvable bags between 25 and 50 pounds. Thus, the mix designs were based on the anticipated bag size range for field use. This research evaluated metakaolin mixes with and without Class C fly ash. Results indicated a seven percent replacement with metakaolin produced concrete with increased strengths and low permeability. When used with Class C fly ash, permeability is reduced to very low rating. Metakaolin may be used to enhance hardened concrete properties for use in high performance concrete (HPC).

Fate of the herbicide glyphosate and its metabolite AMPA in soils and their transfer to surface waters: A multi-scale approach in the Lavaux vineyards, western Switzerland

The use of herbicides in agriculture may lead to environmental problems, such as surface water pollution, with a potential risk for aquatic organisms. The herbicide glyphosate is the most used active ingredient in the world and in Switzerland. In the Lavaux vineyards it is nearly the only molecule applied. This work aimed at studying its fate in soils and its transfer to surface waters, using a multi-scale approach: from molecular (10-9 m) and microscopic scales (10-6 m), to macroscopic (m) and landscape ones (103 m). First of all, an analytical method was developed for the trace level quantification of this widely used herbicide and its main by-product, aminomethylphosphonic acid (AMPA). Due to their polar nature, their derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl) was done prior to their concentration and purification by solid phase extraction. They were then analyzed by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). The method was tested in different aqueous matrices with spiking tests and validated for the matrix effect correction in relevant environmental samples. Calibration curves established between 10 and 1000ng/l showed r2 values above 0.989, mean recoveries varied between 86 and 133% and limits of detection and quantification of the method were as low as 5 and 10ng/l respectively. At the parcel scale, two parcels of the Lavaux vineyard area, located near the Lutrive River at 6km to the east of Lausanne, were monitored to assess to which extent glyphosate and AMPA were retained in the soil or exported to surface waters. They were equipped at their bottom with porous ceramic cups and runoff collectors, which allowed retrieving water samples for the growing seasons 2010 and 2011. Results revealed that the mobility of glyphosate and AMPA in the unsaturated zone was likely driven by the precipitation regime and the soil characteristics, such as slope, porosity structure and layer permeability discrepancy. Elevated glyphosate and AMPA concentrations were measured at 60 and 80 cm depth at parcel bottoms, suggesting their infiltration in the upper parts of the parcels and the presence of preferential flow in the studied parcels. Indeed, the succession of rainy days induced the gradual saturation of the soil porosity, leading to rapid infiltration through macropores, as well as surface runoff formation. Furthermore, the presence of more impervious weathered marls at 100 cm depth induced throughflows, the importance of which for the lateral transport of the herbicide molecules was determined by the slope steepness. Important rainfall events (>10 mm/day) were clearly exporting molecules from the soil top layer, as indicated by important concentrations in runoff samples. A mass balance showed that total loss (10-20%) mainly occurred through surface runoff (96%) and, to a minor extent, by throughflows in soils (4%), with subsequent exfiltration to surface waters. Observations made in the Lutrive River revealed interesting details of glyphosate and AMPA dynamics in urbanized landscapes, such as the Lavaux vineyards. Indeed, besides their physical and chemical properties, herbicide dynamics at the catchment level strongly depend on application rates, precipitation regime, land use and also on the presence of drains or constructed channels. Elevated concentrations, up to 4970 ng/l, observed just after the application, confirmed the diffuse export of these compounds from the vineyard area by surface runoff during main rain events. From April to September 2011, a total load of 7.1 kg was calculated, with 85% coming from vineyards and minor urban sources and 15% from arable crops. Small vineyard surfaces could generate high concentrations of herbicides and contribute considerably to the total load calculated at the outlet, due to their steep slopes (~10%). The extrapolated total amount transferred yearly from the Lavaux vineyards to the Lake of Geneva was of 190kg. At the molecular scale, the possible involvement of dissolved organic matter (DOM) in glyphosate and copper transport was studied using UV/Vis fluorescence spectroscopy. Combined with parallel factor (PARAFAC) analysis, this technique allowed characterizing DOM of soil and surface water samples from the studied vineyard area. Glyphosate concentrations were linked to the fulvic-like spectroscopic signature of DOM in soil water samples, as well as to copper, suggesting the formation of ternary complexes. In surface water samples, its concentrations were also correlated to copper ones, but not in a significant way to the fulvic-like signature. Quenching experiments with standards confirmed field tendencies in the laboratory, with a stronger decrease in fluorescence intensity for fulvic-like fluorophore than for more aromatic ones. Lastly, based on maximum concentrations measured in the river, an environmental risk for these compounds was assessed, using laboratory tests and ecotoxicity data from the literature. In our case and with the methodology applied, the risk towards aquatic species was found negligible (RF<1).

Evaluation of PCC Specification Changes Impact on Durability: 1992 - 1997 Core Study, MLR-98-06, 2005

In 1990, early distress had shown up on US 20 in Hamilton/Webster counties, three years after paving. Since that time, over a dozen more projects, constructed between 1984 and 1994, have been found to exhibit similar early distress. Several changes to the concrete and Portland cement specifications occurred in 1994 and 1996. This study was undertaken to investigate in place concrete pavements before and after specification changes were implemented. The objective of this research is to evaluate the impact of Portland cement and concrete specification changes made in 1994 and 1996 on PCC durability. Cores were obtained in 1998 and 2003 from projects constructed in 1992, before specification changes, and 1997 after specification changes. The following is a brief summary of the conclusions: 1. The pavements in the study constructed under the new specifications are performing much better after 5 years of service than the pavements constructed under the old specifications. 2. According to ISU, micro-cracking is evident in all concrete that has been in service, due to thermal stresses and loading stresses. Also, the low vacuum SEM will desiccate the concrete enough to cause micro-cracking. The SEM should not be used as a tool to indicate micro-cracking. 3. Use of Type II cement (C3A <8%) and a 3.0% SO3 limit does not completely eliminate ettringite infilling in air voids, as indicated in the bottom of the 1997 cores. 4. In areas of high moisture (bottom of the core), infilling is present in most of the 1997 cores. 5. Low air content and high spacing factor in the top of 1992 cores apparently causes F/T cycling cracking and then increased moisture paths from cracking causes infilling. 6. Use of ground granulated blast furnace slag (GGBFS) and fly ash reduces ettringite infilling either by diluting the aluminate (C3A) or lowering permeability, which slows ingress of moisture. 7. The specification changes that made the biggest impact on pavement durability are the limits on vibration and increase in air content in September 1994. 8. Investigations of cores from pavements placed in 2002 and 2003 indicate improved air contents and spacing factors. In-place air content and spacing factors should be monitored to determine if appropriate air void parameters are being met.

Physical performance of biodegradable films intended for antimicrobial food packaging

Antimicrobial films were prepared by including enterocins to alginate, polyvinyl alcohol (PVOH), and zein films. The physical performance of the films was assessed by measuring color, microstructure (SEM), water vapor permeability (WVP), and tensile properties. All studied biopolymers showed poor WVP and limited tensile properties. PVOH showed the best performance exhibiting the lowest WVP values, higher tensile properties, and flexibility among studied biopolymers. SEM of antimicrobial films showed increased presence of voids and pores as a consequence of enterocin addition. However, changes in microstructure did not disturb WVP of films. Moreover, enterocin-containing films showed slight improvement compared to control films. Addition of enterocins to PVOH films had a plasticizing effect, by reducing its tensile strength and increasing the strain at break. The presence of enterocins had an important effect on tensile properties of zein films by significantly reducing its brittleness. Addition of enterocins, thus, proved not to disturb the physical performance of studied biopolymers. Development of new antimicrobial biodegradable packaging materials may contribute to improving food safety while reducing environmental impact derived from packaging waste.

Optimization and Management of Materials in Earthwork Construction, TR-501, 2010

As a result of forensic investigations of problems across Iowa, a research study was developed aimed at providing solutions to identified problems through better management and optimization of the available pavement geotechnical materials and through ground improvement, soil reinforcement, and other soil treatment techniques. The overall goal was worked out through simple laboratory experiments, such as particle size analysis, plasticity tests, compaction tests, permeability tests, and strength tests. A review of the problems suggested three areas of study: pavement cracking due to improper management of pavement geotechnical materials, permeability of mixed-subgrade soils, and settlement of soil above the pipe due to improper compaction of the backfill. This resulted in the following three areas of study: (1) The optimization and management of earthwork materials through general soil mixing of various select and unsuitable soils and a specific example of optimization of materials in earthwork construction by soil mixing; (2) An investigation of the saturated permeability of compacted glacial till in relation to validation and prediction with the Enhanced Integrated Climatic Model (EICM); and (3) A field investigation and numerical modeling of culvert settlement. For each area of study, a literature review was conducted, research data were collected and analyzed, and important findings and conclusions were drawn. It was found that optimum mixtures of select and unsuitable soils can be defined that allow the use of unsuitable materials in embankment and subgrade locations. An improved model of saturated hydraulic conductivity was proposed for use with glacial soils from Iowa. The use of proper trench backfill compaction or the use of flowable mortar will reduce the potential for developing a bump above culverts.

Improving Portland Cement Concrete Mix Consistency and Production Rate through Two-Stage Mixing, TR-505, 2007

A two-stage mixing process for concrete involves mixing a slurry of cementitious materials and water, then adding the slurry to coarse and fine aggregate to form concrete. Some research has indicated that this process might facilitate dispersion of cementitious materials and improve cement hydration, the characteristics of the interfacial transition zone (ITZ) between aggregate and paste, and concrete homogeneity. The goal of the study was to find optimal mixing procedures for production of a homogeneous and workable mixture and quality concrete using a two-stage mixing operation. The specific objectives of the study are as follows: (1) To achieve optimal mixing energy and time for a homogeneous cementitious material, (2) To characterize the homogeneity and flow property of the pastes, (3) To investigate effective methods for coating aggregate particles with cement slurry, (4) To study the effect of the two-stage mixing procedure on concrete properties, (5) To obtain the improved production rates. Parameters measured for Phase I included: heat of hydration, maturity, and rheology tests were performed on the fresh paste samples, and compressive strength, degree of hydration, and scanning electron microscope (SEM) imaging tests were conducted on the cured specimens. For Phases II and III tests included slump and air content on fresh concrete and compressive and tensile strengths, rapid air void analysis, and rapid chloride permeability on hardened concrete.

Performance Evaluation of Concrete Pavement Granular Subbase - Pavement Surface Condition Evaluation, TR-554, 2008

This research project covered a wide range of activities that allowed researchers to understand the relationship between stability, pavement distress, and recycled portland cement concrete (RPCC) subbase aggregate materials. Detailed laboratory and field tests, including pavement distress surveys, were conducted at 26 sites in Iowa. Findings show that specific gravities of RPCC are lower than those of crushed limestone. RPCC aggregate material varies from poorly or well-graded sand to gravel. A modified Micro-Deval test procedure showed that abrasion losses of virgin aggregate materials were within the maximum Micro-Deval abrasion loss of 30% recommended by ASTM D6028-06. Micro-Deval abrasion loss of RPCC aggregate materials, however, was much higher than that of virgin materials and exceeded 30% loss. Modulus of elasticity of RPCC subbase materials is high but variable. RPCC subbase layers normally have low permeability. The pavement surfaces for both virgin and RPCC subbase across Iowa were evaluated to fulfill the objectives of this study related to field evaluation. Visual distress surveys were conducted to gather the detailed current pavement condition information including the type, extent, and severity of the pavement distresses. The historical pavement condition information for the surveyed field sections was extracted from the Iowa DOT's Pavement Management Information System (PMIS). The current surface condition of existing field pavements with RPCC subbase was compared with the virgin aggregate subbase sections using two different approaches. The changes in pavement condition indices (PCI and IRI) with time for both types of pavements (subbases) were compared.

The Deleterious Chemical Effects of Concentrated Deicing Solutions on Portland Cement Concrete, TR-480, 2008

This research project investigated the effects of concentrated brines of magnesium chloride, calcium chloride, sodium chloride, and calcium magnesium acetate on portland cement concrete. Although known to be effective at deicing and anti-icing, the deleterious effects these chemicals may have on concrete have not been well documented. As a result of this research, it was determined that there is significant evidence that magnesium chloride and calcium chloride chemically interact with hardened portland cement paste in concrete resulting in expansive cracking, increased permeability, and a significant loss in compressive strength. Although the same effects were not seen with sodium chloride brines, it was shown that sodium chloride brines have the highest rate of ingress into hardened concrete. This latter fact is significant with respect to corrosion of embedded steel. The mechanism for attack of hardened cement paste varies with deicer chemical but in general, a chemical reaction between chlorides and cement hydration products results in the dissolution of the hardened cement paste and formation of oxychloride phases, which are expansive. The chemical attack of the hardened cement paste is significantly reduced if supplementary cementitious materials are included in the concrete mixture. Both coal fly ash and ground granulated blast furnace slag were found to be effective at mitigating the chemical attack caused by the deicers tested. In the tests performed, ground granulated blast furnace slag performed better as a mitigation strategy as compared to coal fly ash. Additionally, siloxane and silane sealants were effective at slowing the ingress of deicing chemicals into the concrete and thereby reducing the observed distress. In general, the siloxane sealant appeared to be more effective than the silane, but both were effective and should be considered as a maintenance strategy.