Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

Different outcomes of a cardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction.

INTRODUCTION: Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO2) and exercise duration, of an EBCR programme in AMI survivors. METHODS: Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO2 and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO2 and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO2 (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO2. CONCLUSION: A phase II EBCR programme was associated with significant improvements in pVO2 and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

Predicting the effectiveness of different mulching techniques in reducing post-fire runoff and erosion at plot scale with the RUSLE, MMF and PESERA models.

Wildfires have become a recurrent threat for many Mediterranean forest ecosystems. The characteristics of the Mediterranean climate, with its warm and dry summers and mild and wet winters, make this a region prone to wildfire occurrence as well as to post-fire soil erosion. This threat is expected to be aggravated in the future due to climate change and land management practices and planning. The wide recognition of wildfires as a driver for runoff and erosion in burnt forest areas has created a strong demand for model-based tools for predicting the post-fire hydrological and erosion response and, in particular, for predicting the effectiveness of post-fire management operations to mitigate these responses. In this study, the effectiveness of two post-fire treatments (hydromulch and natural pine needle mulch) in reducing post-fire runoff and soil erosion was evaluated against control conditions (i.e. untreated conditions), at different spatial scales. The main objective of this study was to use field data to evaluate the ability of different erosion models: (i) empirical (RUSLE), (ii) semi-empirical (MMF), and (iii) physically-based (PESERA), to predict the hydrological and erosive response as well as the effectiveness of different mulching techniques in fire-affected areas. The results of this study showed that all three models were reasonably able to reproduce the hydrological and erosive processes occurring in burned forest areas. In addition, it was demonstrated that the models can be calibrated at a small spatial scale (0.5 m2) but provide accurate results at greater spatial scales (10 m2). From this work, the RUSLE model seems to be ideal for fast and simple applications (i.e. prioritization of areas-at-risk) mainly due to its simplicity and reduced data requirements. On the other hand, the more complex MMF and PESERA models would be valuable as a base of a possible tool for assessing the risk of water contamination in fire-affected water bodies and for testing different land management scenarios.

A HER2 selective theranostic agent for surgical resection guidance and photodynamic therapy.

In many cancers early intervention involves surgical resection of small localised tumour masses. Inadequate resection leads to recurrence whereas overzealous treatment can lead to organ damage. This work describes production of a HER2 targeting antibody Fab fragment dual conjugated to achieve both real time near-infrared fluorescent imaging and photodynamic therapy. The use of fluorescence emission from a NIR-dye could be used to guide resection of tumour bulk, for example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this would then be followed by activation of the photodynamic therapeutic agent to destroy untreated localised areas of cancer infiltration and tumour infiltrated lymph nodes. This theranostic agent was prepared from the Fab fragment of trastuzumab initially by functional disulfide re-bridging and site-specific click reaction of a NIR-dye. This was followed by further reaction with a novel pre-activated form of the photosensitiser chlorin e6 with the exposed fragments' lysine residues. Specific binding of the theranostic agent was observed in vitro with a HER2 positive cell line and cellular near-infrared fluorescence was observed with flow cytometry. Specific photo-activity of the conjugates when exposed to laser light was observed with HER2 positive but not HER2 negative cell lines in vitro, this selectivity was not seen with the unconjugated drug. This theranostic agent demonstrates that two different photo-active functions can be coupled to the same antibody fragment with little interference to their independent activities.

A theoretical investigation of internal conversion in 1,2-dithiane using non-adiabatic multiconfigurational molecular dynamics.

Non-adiabatic multiconfigurational molecular dynamics simulations have revealed a molecular "Newton's Cradle" that activates on absorption of light in the mid-UV and assists the S1/S0 internal conversion process in 1,2-dithiane, protecting the disulfide bond from photodamage. This communication challenges contemporary understanding of the S1/S0 internal conversion process in 1,2-dithiane and presents a classically-intuitive reinterpretation of experimental evidence.

Using the soil and water assessment tool to estimate dissolved inorganic nitrogen water pollution abatement cost functions in central portugal.

Coastal aquatic ecosystems are increasingly affected by diffuse source nutrient water pollution from agricultural activities in coastal catchments, even though these ecosystems are important from a social, environmental and economic perspective. To warrant sustainable economic development of coastal regions, we need to balance marginal costs from coastal catchment water pollution abatement and associated marginal benefits from coastal resource appreciation. Diffuse-source water pollution abatement costs across agricultural sectors are not easily determined given the spatial heterogeneity in biophysical and agro-ecological conditions as well as the available range of best agricultural practices (BAPs) for water quality improvement. We demonstrate how the Soil and Water Assessment Tool (SWAT) can be used to estimate diffuse-source water pollution abatement cost functions across agricultural land use categories based on a stepwise adoption of identified BAPs for water quality improvement and corresponding SWAT-based estimates for agricultural production, agricultural incomes, and water pollution deliveries. Results for the case of dissolved inorganic nitrogen (DIN) surface water pollution by the key agricultural land use categories ("annual crops," "vineyards," and "mixed annual crops & vineyards") in the Vouga catchment in central Portugal show that no win-win agricultural practices are available within the assessed BAPs for DIN water quality improvement. Estimated abatement costs increase quadratically in the rate of water pollution abatement, with largest abatement costs for the "mixed annual crops & vineyards" land use category (between 41,900 and 51,900 € tDIN yr) and fairly similar abatement costs across the "vineyards" and "annual crops" land use categories (between 7300 and 15,200 € tDIN yr).

Rehybridization dynamics into the pericyclic minimum of an electrocyclic reaction imaged in real-time.

Electrocyclic reactions are characterized by the concerted formation and cleavage of both σ and π bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule α-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated π bonds. The σ bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general.

Post-fire overland flow generation and inter-rill erosion under simulated rainfall in two eucalypt stands in north-central Portugal.

The aim of this study was to improve the existing knowledge of the runoff and inter-rill erosion response of forest stands following wildfire, focusing on commercial eucalypt plantations and employing field rainfall simulation experiments (RSE's). Repeated RSE's were carried out in two adjacent but contrasting eucalypt stands on steep hill slopes in north-central Portugal that suffered a moderate severity fire in July 2005. This was done at six occasions ranging from 3 to 24 months after the fire and using a paired-plot experimental design that comprised two pairs of RSE's at each site and occasion. Of the 46 RSE's: (i) 24 and 22 RSE's involved application rates of 45-50 and 80-85 mm h(-1), respectively; (ii) 22 took place in a stand that had been ploughed in down slope direction several years before the wildfire and 24 in an unploughed stand. The results showed a clear tendency for extreme-intensity RSE's to produce higher runoff amounts and greater soil and organic matter losses than the simultaneous high-intensity RSE's on the neighbouring plots. However, there existed marked exceptions, both in space (for one of the plot pairs) and time (under intermediate soil water repellency conditions). Also, overland flow generation and erosion varied significantly between the various field campaigns. This temporal pattern markedly differed from a straightforward decline with time-after-fire and rather suggested a seasonal component, reflecting broad variations in topsoil water repellency. The ploughed site produced less runoff and erosion than the unploughed site, contrary to what would be expected if the down slope ploughing had occurred after the wildfire instead of several years before it. Finally, sediment losses at both study sites were noticeably lower than those reported by other studies involving repeat RSE's, i.e. in Australia and western Spain. This possibly reflected a history of intensive land use in the study region, including in more recent times after the widespread introduction of eucalypt plantations.

Assessing impacts of future climate change on extreme fire weather and pyro-regions in Iberian Peninsula.

Weather conditions play an important role in wildfire activity. In many regions, future climate could lead to different fire weather, with impacts on the ignition, behaviour, and suppression of wildfires, which may, therefore, force new fire regimes. This study aimed to assess the evolution of fire weather indices and the Number of Extreme Days (NED) in the context of climate change. We estimated the impact of these changes on monthly Normalized Burnt Area (NBA) and in the spatial distribution of Pyro-Regions (PR), using a recently identified relationship between NED and NBA intra-annual patterns. The components of the Canadian Forest Fire Weather Index System (CFFWIS) in the Iberian Peninsula were analysed for present-day conditions and future climate scenarios, using daily data from ERA-Interim (1980-2014) and an ensemble of simulations from 11 EURO-CORDEX high spatial resolution models, for two future periods (2041-2070 and 2071-2100) and scenarios (RCP4.5 and RCP8.5). Results suggest a significant increase in future fire weather risk, especially in late spring and early autumn, and also in southern and eastern Iberian Peninsula. NED is expected to strongly increase in summer months in the four PRs, but also to decrease in March and April in the northwestern and southwestern PR. This could change the spatial distribution of PRs, with a general northwards movement: the northern PR is expected to disappear except north of the Cantabrian Mountains, being replaced by the northwestern PR; the southwestern PR is expected to grow and occupy part of the area currently in the northwestern PR; and a new PR could appear in parts of the current eastern PR. These PR changes follow the projected modifications in the major climate regions. Results suggest different fire regimes in the future, with higher fire weather risk, and a longer and harsher fire season.

Imaging the short-lived hydroxyl-hydronium pair in ionized liquid water.

The radiolysis of water is ubiquitous in nature and plays a critical role in numerous biochemical and technological applications. Although the elementary reaction pathways for ionized water have been studied, the short-lived intermediate complex and structural dynamic response after the proton transfer reaction remain poorly understood. Using a liquid-phase ultrafast electron diffraction technique to measure the intermolecular oxygen···oxygen and oxygen···hydrogen bonds, we captured the short-lived radical-cation complex OH(H3O+) that was formed within 140 femtoseconds through a direct oxygen···oxygen bond contraction and proton transfer, followed by the radical-cation pair dissociation and the subsequent structural relaxation of water within 250 femtoseconds. These measurements provide direct evidence of capturing this metastable radical-cation complex before separation, thereby improving our fundamental understanding of elementary reaction dynamics in ionized liquid water.

Conformer-specific photochemistry imaged in real space and time.

Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution of a specific set of α-phellandrene conformers into the product isomer predicted by the Woodward-Hoffmann rules in real space and time. Our experimental results are in quantitative agreement with nonadiabatic quantum molecular dynamics simulations, which provide considerable detail of how conformation influences the time scale and quantum efficiency of photoinduced ring-opening reactions.

Photodissociation of aqueous I 3 - observed with liquid-phase ultrafast mega-electron-volt electron diffraction.

Developing femtosecond resolution methods for directly observing structural dynamics is critical to understanding complex photochemical reaction mechanisms in solution. We have used two recent developments, ultrafast mega-electron-volt electron sources and vacuum compatible sub-micron thick liquid sheet jets, to enable liquid-phase ultrafast electron diffraction (LUED). We have demonstrated the viability of LUED by investigating the photodissociation of tri-iodide initiated with a 400 nm laser pulse. This has enabled the average speed of the bond expansion to be measured during the first 750 fs of dissociation and the geminate recombination to be directly captured on the picosecond time scale.

Liquid-phase mega-electron-volt ultrafast electron diffraction.

The conversion of light into usable chemical and mechanical energy is pivotal to several biological and chemical processes, many of which occur in solution. To understand the structure-function relationships mediating these processes, a technique with high spatial and temporal resolutions is required. Here, we report on the design and commissioning of a liquid-phase mega-electron-volt (MeV) ultrafast electron diffraction instrument for the study of structural dynamics in solution. Limitations posed by the shallow penetration depth of electrons and the resulting information loss due to multiple scattering and the technical challenge of delivering liquids to vacuum were overcome through the use of MeV electrons and a gas-accelerated thin liquid sheet jet. To demonstrate the capabilities of this instrument, the structure of water and its network were resolved up to the 3 rd hydration shell with a spatial resolution of 0.6 Å; preliminary time-resolved experiments demonstrated a temporal resolution of 200 fs.

Femtosecond gas-phase mega-electron-volt ultrafast electron diffraction.

The development of ultrafast gas electron diffraction with nonrelativistic electrons has enabled the determination of molecular structures with atomic spatial resolution. It has, however, been challenging to break the picosecond temporal resolution barrier and achieve the goal that has long been envisioned-making space- and-time resolved molecular movies of chemical reaction in the gas-phase. Recently, an ultrafast electron diffraction (UED) apparatus using mega-electron-volt (MeV) electrons was developed at the SLAC National Accelerator Laboratory for imaging ultrafast structural dynamics of molecules in the gas phase. The SLAC gas-phase MeV UED has achieved 65 fs root mean square temporal resolution, 0.63 Å spatial resolution, and 0.22 Å-1 reciprocal-space resolution. Such high spatial-temporal resolution has enabled the capturing of real-time molecular movies of fundamental photochemical mechanisms, such as chemical bond breaking, ring opening, and a nuclear wave packet crossing a conical intersection. In this paper, the design that enables the high spatial-temporal resolution of the SLAC gas phase MeV UED is presented. The compact design of the differential pump section of the SLAC gas phase MeV UED realized five orders-of-magnitude vacuum isolation between the electron source and gas sample chamber. The spatial resolution, temporal resolution, and long-term stability of the apparatus are systematically characterized.

The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction.

The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subångström length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale.

Impacts of climate and land use changes on the water quality of a small Mediterranean catchment with intensive viticulture.

Studies that address the potential effects of climate and land use changes on surface water quality are scarce in the Mediterranean region. In the present work, the impacts of climate and land use changes on nutrient and copper exports from a humid Mediterranean catchment (São Lourenço) were evaluated using the SWAT model. SWAT reproduced reasonably well total nitrogen (TN), phosphorus (TP) and copper (Cu) exports in São Lourenço, providing an adequate baseline scenario as well as a suitable model parameterization for assessing the impacts of climate and land use changes under the A1B and B1 emission scenarios for the end of the 21st century (2071-2100). Land use changes scenarios were generated along the same storylines as climate change scenarios to assess the combined effects of the two stressors. Climate changes itself led to a decline in annual TN and TP exports under both emission scenarios mostly due to a decrease in runoff and erosion induced by a reduction in rainfall, but it hardly affected Cu exports largely due to its strong immobilization in soils. Land use changes per se resulted in an increase in streamflow, but the changes in water quality varied markedly according to the scenarios. A substantial decrease in TN, TP and Cu exports was observed under scenario A1B, due to a reduction in vineyard areas. Under scenario B1, however, TP exports decreased much less while TN exports hardly changed, reflecting differences in the preferential transport pathways of these compounds. Cu exports also remained the same, as no changes occurred in the vineyard areas. The combination of climate and land use change scenarios revealed additive impacts on the exports of all three contaminants, emphasizing the importance of integrated approaches to define adaptive land management practices that can ensure the future sustainability of Mediterranean water resources.

Impacts of climate and land use changes on the hydrological and erosion processes of two contrasting Mediterranean catchments.

The impacts of climate and land use changes on streamflow and sediment export were evaluated for a humid (São Lourenço) and a dry (Guadalupe) Mediterranean catchment, using the SWAT model. SWAT was able to produce viable streamflow and sediment export simulations for both catchments, which provided a baseline for investigating climate and land use changes under the A1B and B1 emission scenarios for 2071-2100. Compared to the baseline scenario (1971-2000), climate change scenarios showed a decrease in annual rainfall for both catchments (humid: -12%; dry: -8%), together with strong increases in rainfall during winter. Land use changes were derived from a socio-economic storyline in which traditional agriculture is replaced by more profitable land uses (i.e. corn and commercial forestry at the humid site; sunflower at the dry site). Climate change projections showed a decrease in streamflow for both catchments, whereas sediment export decreased only for the São Lourenço catchment. Land use changes resulted in an increase in streamflow, but the erosive response differed between catchments. The combination of climate and land use change scenarios led to a reduction in streamflow for both catchments, suggesting a domain of the climatic response. As for sediments, contrasting results were observed for the humid (A1B: -29%; B1: -22%) and dry catchment (A1B: +222%; B1: +5%), which is mainly due to differences in the present-day and forecasted vegetation types. The results highlight the importance of climate-induced land-use change impacts, which could be similar to or more severe than the direct impacts of climate change alone.

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. DESIGN AND METHODS: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. CONCLUSIONS: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

The effectiveness of alpha 2-adrenoceptor activation increases from the distal to the proximal part of the veins of canine limbs.

1. The effectiveness of alpha 1- and alpha 2-adrenoceptor activation was compared at different levels of the saphenous and cephalic vein of the dog in vitro. 2. Helically cut strips were used to determine concentration-response curves to phenylephrine, noradrenaline, UK-14,304 (5-bromo-6-(imidazoline-2-ylamino)-quinoxaline) and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d-azepine). The effect of prazosin and yohimbine on these curves was also studied. 3. At the distal level, the maximum response to UK-14,304 amounted to 33 and 50% of those to noradrenaline in the saphenous and cephalic vein, respectively, while at the proximal level the maximum response to UK-14,304 amounted to 72 and 78% of those to noradrenaline, in the saphenous and cephalic vein, respectively. 4. In both vessels, the results obtained with B-HT 920 were very similar to those for UK-14,304. 5. The pD2 values for UK-14,304 - which were identical at the three levels of both vessels - and the pA2 values for the antagonism exerted by either prazosin or yohimbine against the responses to UK-14,304 indicate that the alpha 2-adrenoceptors are identical at the different levels of both vessels. 6. These results show that the effectiveness of alpha 2-adrenoceptor stimulation increases from the distal to the proximal regions of canine limb veins. Apparently, this is due to a greater density of alpha 2-adrenoceptors in the proximal regions. 7. Yohimbine is much more potent against phenylephrine distally than proximally in both vessels. However, after 30 nm phenoxybenzamine - a concentration which eliminates the vast majority of alpha,-adrenoceptors without affecting alpha 2-adrenoceptors - yohimbine became equally potent at both levels, suggesting that the difference existing before phenoxybenzamine depended on alpha,-adrenoceptors. Hence it is concluded that alpha,-adrenoceptors in distal and proximal portions may differ.

Central alpha 2-adrenoceptors and blood pressure regulation in the rat.

The role of alpha 2-adrenoceptors in the central regulation of blood pressure has been questioned, since drugs such as clonidine stimulate both alpha 2-adrenoceptors and imidazoline-preferring receptors. The present work was undertaken to study the influence of alpha 2D-adrenoceptors, encoded by the RG20 gene, on blood pressure in the rat. An antisense phosphodiester oligodeoxynucleotide, directed at nucleotides 4-21 of the RG20 gene, was injected in the right lateral cerebral ventricle, causing an increase in systolic blood pressure, both at 1 and 2 days after the injection, when compared to groups of control rats (injected with the sense oligodeoxynucleotide or a missense oligodeoxynucleotide or distilled water). Antisense oligodeoxynucleotides directed either at nucleotides 65-82 of the RG10 gene (encoding for alpha 2C-adrenoceptors) or at nucleotides 26-43 of the RNG gene (encoding for alpha 2B-adrenoceptors), failed to produce any change in blood pressure after being injected. We conclude that the alpha 2-adrenoceptor encoded by the RG20 gene may play a role in blood pressure regulation in the rat.