Supramolecular Organization of Heptapyrenotide Oligomers—An in Depth Investigation by Molecular Dynamics Simulations

We present a molecular modeling study based on ab initio and classical molecular dynamics calculations, for the investigation of the tridimensional structure and supramolecular assembly formation of heptapyrenotide oligomers in water solution. Our calculations show that free oligomers self-assemble in helical structures characterized by an inner core formed by π- stacked pyrene units, and external grooves formed by the linker moieties. The coiling of the linkers has high ordering, dominated by hydrogen-bond interactions among the phosphate and amide groups. Our models support a mechanism of longitudinal supramolecular oligomerization based on interstrand pyrene intercalation. Only a minimal number of pyrene units intercalate at one end, favoring formation of very extended longitudinal chains, as also detected by AFM experiment. Our results provide a structural explanation of the mechanism of chirality amplification in 1:1 mixtures of standard heptapyrenotides and modified oligomers with covalently linked deoxycytidine, based on selective molecular recognition and binding of the nucleotide to the groove of the left-wound helix.

Is there a ‚Depth versus Participation‘ Dilemma in International Cooperation?

Much of the International Relations literature assumes that there is a “depth versus participation” dilemma in international politics: shallower international agreements attract more countries and greater depth is associated with less participation. We argue that this conjecture is too simple and probably misleading because the depth of any given cooperative effort is in fact multidimensional. This multidimensionality manifests itself in the design characteristics of international agreements: in particular, the specificity of obligations, monitoring and enforcement mechanisms, dispute settlement mechanisms, positive incentives (assistance), and organizational structures (secretariats). We theorize that the first three of these design characteristics have negative and the latter three have positive effects on participation in international cooperative efforts. Our empirical testing of these claims relies on a dataset that covers more than 200 global environmental treaties. We find a participation-limiting effect for the specificity of obligations, but not for monitoring and enforcement. In contrast, we observe that assistance provisions in treaties have a significant and substantial positive effect on participation. Similarly, dispute settlement mechanisms tend to promote treaty participation. The main implication of our study is that countries do not appear to stay away from agreements with monitoring and enforcement provisions, but that the inclusion of positive incentives and dispute settlement mechanisms can promote international cooperation. In other words, our findings suggest that policymakers do not necessarily need to water down global treaties in order to obtain more participation.

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth

BACKGROUND Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection. Objectives: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas. METHODS We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. RESULTS Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor. CONCLUSIONS Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection.

The optimal lead insertion depth for esophageal ECG recordings with respect to atrial signal quality

BACKGROUND Diagnosing supraventricular arrhythmias by conventional long-term ECG can be cumbersome because of poor p-waves. Esophageal long-term electrocardiography (eECG) has an excellent sensitivity for atrial signals and may overcome this limitation. However, the optimal lead insertion depth (OLID) is not known. METHODS We registered eECGs at different lead insertion depths in 27 patients and analyzed 199,716 atrial complexes with respect to signal amplitude and slope. Correlation and regression analyses were used to find a criterion for OLID. RESULTS Atrial signal amplitudes and slopes significantly depend on lead insertion depth. OLID correlates with body height (rSpearman=0.71) and can be estimated by OLID [cm]=0.25*body height[cm]-7cm. At this insertion depth, we recorded the largest esophageal atrial signal amplitudes (1.27±0.86mV), which were much larger compared to conventional surface lead II (0.19±0.10mV, p<0.0001). CONCLUSION The OLID depends on body height and can be calculated by a simple regression formula.

The influence of yield surface shape and damage in the depth-dependent response of bone tissue to nanoindentation using spherical and Berkovich indenters

Prevention and treatment of osteoporosis rely on understanding of the micromechanical behaviour of bone and its influence on fracture toughness and cell-mediated adaptation processes. Postyield properties may be assessed by nonlinear finite element simulations of nanoindentation using elastoplastic and damage models. This computational study aims at determining the influence of yield surface shape and damage on the depth-dependent response of bone to nanoindentation using spherical and conical tips. Yield surface shape and damage were shown to have a major impact on the indentation curves. Their influence on indentation modulus, hardness, their ratio as well as the elastic-to-total work ratio is well described by multilinear regressions for both tip shapes. For conical tips, indentation depth was not statistically significant (p<0.0001). For spherical tips, damage was not a significant parameter (p<0.0001). The gained knowledge can be used for developing an inverse method for identification of postelastic properties of bone from nanoindentation.

Cell and matrix morphology in articular cartilage from adult human knee and ankle joints suggests depth-associated adaptations to biomechanical and anatomical roles

OBJECTIVE Marked differences exist between human knee and ankle joints regarding risks and progression of osteoarthritis (OA). Pathomechanisms of degenerative joint disease may therefore differ in these joints, due to differences in tissue structure and function. Focussing on structural issues which are design goals for tissue engineering, we compared cell and matrix morphologies in different anatomical sites of adult human knee and ankle joints. METHODS Osteochondral explants were acquired from knee and ankle joints of deceased persons aged 20 to 40 years and analyzed for cell, matrix and tissue morphology using confocal and electron microscopy and unbiased stereological methods. Variations associated with joint (knee versus ankle) and biomechanical role (convex versus concave articular surfaces) were identified by 2-way analysis of variance and post-hoc analysis. RESULTS Knee cartilage exhibited higher cell densities in the superficial zone than ankle cartilage. In the transitional zone, higher cell densities were observed in association with convex versus concave articular surfaces, without significant differences between knee and ankle cartilage. Highly uniform cell and matrix morphologies were evident throughout the radial zone in the knee and ankle, regardless of tissue biomechanical role. Throughout the knee and ankle cartilage sampled, chondron density was remarkably constant at approximately 4.2×10(6) chondrons/cm(3). CONCLUSION Variation of cartilage cell and matrix morphologies with changing joint and biomechanical environments suggests that tissue structural adaptations are performed primarily by the superficial and transitional zones. Data may aid the development of site-specific cartilage tissue engineering, and help identify conditions where OA is likely to occur.

Reconstructing the subsurface ocean decadal variability using surface nudging in a perfect model framework

Initialising the ocean internal variability for decadal predictability studies is a new area of research and a variety of ad hoc methods are currently proposed. In this study, we explore how nudging with sea surface temperature (SST) and salinity (SSS) can reconstruct the threedimensional variability of the ocean in a perfect model framework. This approach builds on the hypothesis that oceanic processes themselves will transport the surface information into the ocean interior as seen in ocean-only simulations. Five nudged simulations are designed to reconstruct a 150 years ‘‘target’’ simulation, defined as a portion of a long control simulation. The nudged simulations differ by the variables restored to, SST or SST + SSS, and by the area where the nudging is applied. The strength of the heat flux feedback is diagnosed from observations and the restoring coefficients for SSS use the same time-scale. We observed that this choice prevents spurious convection at high latitudes and near sea-ice border when nudging both SST and SSS. In the tropics, nudging the SST is enough to reconstruct the tropical atmosphere circulation and the associated dynamical and thermodynamical impacts on the underlying ocean. In the tropical Pacific Ocean, the profiles for temperature show a significant correlation from the surface down to 2,000 m, due to dynamical adjustment of the isopycnals. At mid-tohigh latitudes, SSS nudging is required to reconstruct both the temperature and the salinity below the seasonal thermocline. This is particularly true in the North Atlantic where adding SSS nudging enables to reconstruct the deep convection regions of the target. By initiating a previously documented 20-year cycle of the model, the SST + SSS nudging is also able to reproduce most of the AMOC variations, a key source of decadal predictability. Reconstruction at depth does not significantly improve with amount of time spent nudging and the efficiency of the surface nudging rather depends on the period/events considered. The joint SST + SSS nudging applied verywhere is the most efficient approach. It ensures that the right water masses are formed at the right surface density, the subsequent circulation, subduction and deep convection further transporting them at depth. The results of this study underline the potential key role of SSS for decadal predictability and further make the case for sustained largescale observations of this field.

No shift to a deeper water uptake depth in response to summer drought of two lowland and sub-alpine C3-grasslands in Switzerland

Temperate C3-grasslands are of high agricultural and ecological importance in Central Europe. Plant growth and consequently grassland yields depend strongly on water supply during the growing season, which is projected to change in the future. We therefore investigated the effect of summer drought on the water uptake of an intensively managed lowland and an extensively managed sub-alpine grassland in Switzerland. Summer drought was simulated by using transparent shelters. Standing above- and belowground biomass was sampled during three growing seasons. Soil and plant xylem waters were analyzed for oxygen (and hydrogen) stable isotope ratios, and the depths of plant water uptake were estimated by two different approaches: (1) linear interpolation method and (2) Bayesian calibrated mixing model. Relative to the control, aboveground biomass was reduced under drought conditions. In contrast to our expectations, lowland grassland plants subjected to summer drought were more likely (43–68 %) to rely on water in the topsoil (0–10 cm), whereas control plants relied less on the topsoil (4–37 %) and shifted to deeper soil layers (20–35 cm) during the drought period (29–48 %). Sub-alpine grassland plants did not differ significantly in uptake depth between drought and control plots during the drought period. Both approaches yielded similar results and showed that the drought treatment in the two grasslands did not induce a shift to deeper uptake depths, but rather continued or shifted water uptake to even more shallower soil depths. These findings illustrate the importance of shallow soil depths for plant performance under drought conditions.

Tracking water pathways in steep hillslopes by d18O depth profiles of soil water

Assessing temporal variations in soil water flow is important, especially at the hillslope scale, to identify mechanisms of runoff and flood generation and pathways for nutrients and pollutants in soils. While surface processes are well considered and parameterized, the assessment of subsurface processes at the hillslope scale is still challenging since measurement of hydrological pathways is connected to high efforts in time, money and personnel work. The latter might not even be possible in alpine environments with harsh winter processes. Soil water stable isotope profiles may offer a time-integrating fingerprint of subsurface water pathways. In this study, we investigated the suitability of soil water stable isotope (d18O) depth profiles to identify water flow paths along two transects of steep subalpine hillslopes in the Swiss Alps. We applied a one-dimensional advection–dispersion model using d18O values of precipitation (ranging from _24.7 to _2.9‰) as input data to simulate the d18O profiles of soil water. The variability of d18O values with depth within each soil profile and a comparison of the simulated and measured d18O profiles were used to infer information about subsurface hydrological pathways. The temporal pattern of d18O in precipitation was found in several profiles, ranging from _14.5 to _4.0‰. This suggests that vertical percolation plays an important role even at slope angles of up to 46_. Lateral subsurface flow and/or mixing of soil water at lower slope angles might occur in deeper soil layers and at sites near a small stream. The difference between several observed and simulated d18O profiles revealed spatially highly variable infiltration patterns during the snowmelt periods: The d18O value of snow (_17.7 ± 1.9‰) was absent in several measured d18O profiles but present in the respective simulated d18O profiles. This indicated overland flow and/or preferential flow through the soil profile during the melt period. The applied methods proved to be a fast and promising tool to obtain time-integrated information on soil water flow paths at the hillslope scale in steep subalpine slopes.