C-SPADE : a web-tool for interactive analysis and visualization of drug screening experiments through compound-specific bioactivity dendrograms

The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds' multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at http://cspade.fimm.fi/.Peer reviewe

Flexural behavior of steel fiber reinforced concrete: testing and modelling

In this paper the results of tests performed on specimens and structural elements made of steel fiber reinforced concrete are presented. Fiber content ranged from 0 to 60 kg/m3 of concrete. Using the results of the uniaxial compression tests performed under displacement control condition, a stress strain relationship for fiber concrete in compression was derived. Three point bending tests on notched beams were carried out in order to simulate the post cracking behavior and to evaluate the fracture energy. Based on the constitutive relationships derived from the experiments, a layered model for the analysis of steel fiber reinforced concrete cross sections was developed. The model performance and the benefits of fiber reinforcement on thin slabs reinforced with steel bars were assessed by carrying out tests on slab strips. The main results are presented and discussed

Global warming-induced upper-ocean freshening and the intensification of super typhoons

Super typhoons (STYs), intense tropical cyclones of the western North Pacific, rank among the most destructive natural hazards globally. The violent winds of these storms induce deep mixing of the upper ocean, resulting in strong sea surface cooling and making STYs highly sensitive to ocean density stratification. Although a few studies examined the potential impacts of changes in ocean thermal structure on future tropical cyclones, they did not take into account changes in near-surface salinity. Here, using a combination of observations and coupled climate model simulations, we show that freshening of the upper ocean, caused by greater rainfall in places where typhoons form, tends to intensify STYs by reducing their ability to cool the upper ocean. We further demonstrate that the strengthening effect of this freshening over the period 1961–2008 is ∼53% stronger than the suppressive effect of temperature, whereas under twenty-first century projections, the positive effect of salinity is about half of the negative effect of ocean temperature changes.United States. Dept. of Energy. Regional & Global Climate Modeling Progra

Contribution of hurricane-induced sediment resuspension to coastal oxygen dynamics

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 8 (2018): 15740, doi:10.1038/s41598-018-33640-3.Hurricanes passing over the ocean can mix the water column down to great depths and resuspend massive volumes of sediments on the continental shelves. Consequently, organic carbon and reduced inorganic compounds associated with these sediments can be resuspended from anaerobic portions of the seabed and re-exposed to dissolved oxygen (DO) in the water column. This process can drive DO consumption as sediments become oxidized. Previous studies have investigated the effect of hurricanes on DO in different coastal regions of the world, highlighting the alleviation of hypoxic conditions by extreme winds, which drive vertical mixing and re-aeration of the water column. However, the effect of hurricane-induced resuspended sediments on DO has been neglected. Here, using a diverse suite of datasets for the northern Gulf of Mexico, we find that in the few days after a hurricane passage, decomposition of resuspended shelf sediments consumes up to a fifth of the DO added to the bottom of the water column during vertical mixing. Despite uncertainty in this value, we highlight the potential significance of this mechanism for DO dynamics. Overall, sediment resuspension likely occurs over all continental shelves affected by tropical cyclones, potentially impacting global cycles of marine DO and carbon.Support for J. Moriarty was provided by the USGS Mendenhall Program

Effect of Intravenous Phenobarbital on Left Ventricular Myocardial Contractility Determined by Echocardiography in Children

Introduction. Animal studies and rare human studies have suggesteda negative effect of barbiturates on cardiac function. Althoughintravenous (IV) phenobarbital is used routinely in children in theclinical setting, studies in children are lacking. We performed a studyto evaluate effect of IV phenobarbital loading on myocardial systolicfunction of children.Methods.xIn a prospective pilot study in children without congenitalheart defects, the effect of IV phenobarbital was evaluated on theleft ventricular systolic function measured by ejection fraction (EF)by Simpson’s method via an echocardiogram. Any child less than 18years of age who received IV loading dose of at least 20 mg/kg ofphenobarbital given as an infusion over 20 - 30 minutes for variousmedical indications was eligible to take part in the study. Three measurementsof EF by an echocardiogram were made: before loadingdose, 30 minutes after completion of the loading dose, and prior tothe first maintenance dose. Relevant clinical data were recorded,including vital signs, immediately prior to each echocardiogram.Change of function as measured by EF over time was analyzed usinglinear mixed modeling methods. For this study, significant change inblood pressure was defined as a drop of at least 20 mmHg in systolicblood pressure.Results. Ten children (70% female, age range two days to 8.2 years)were enrolled. Three had hypotension with a drop of systolic bloodpressure greater than 20 mmHg from baseline. On examining thetrajectory of EF on each individual graphically, the left ventricularEF tended to fall immediately following phenobarbital therapy andreturn to baseline on re-evaluation. These trajectories were statisticallysignificant for EF.Conclusions. Phenobarbital had a direct and transient depressanteffect on systolic function of the myocardium in one third of the cases.The depression in EF appeared to be transient with return to baseline in less than 24 hours. We recommend close monitoring with anticipationof decreased function in children when using IV phenobarbital.Kans J Med 2019;12(2):40-44

Linking deep convection and phytoplankton blooms in the northern Labrador Sea in a changing climate

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 13 (2018): e0191509, doi:10.1371/journal.pone.0191509.Wintertime convective mixing plays a pivotal role in the sub-polar North Atlantic spring phytoplankton blooms by favoring phytoplankton survival in the competition between light-dependent production and losses due to grazing and gravitational settling. We use satellite and ocean reanalyses to show that the area-averaged maximum winter mixed layer depth is positively correlated with April chlorophyll concentration in the northern Labrador Sea. A simple theoretical framework is developed to understand the relative roles of winter/spring convection and gravitational sedimentation in spring blooms in this region. Combining climate model simulations that project a weakening of wintertime Labrador Sea convection from Arctic sea ice melt with our framework suggests a potentially significant reduction in the initial fall phytoplankton population that survive the winter to seed the region’s spring bloom by the end of the 21st century.KB, LB, PJR and LRL were supported by the Office of Science (BER), U. S. Department of Energy as part of the Regional and Global Climate Modelling (RGCM) Program. SCD acknowledges support from NASA Award NNX15AE65G North Atlantic Aerosol and Marine Ecosystem Study (NAAMES)

ROOT ANALOGUE IMPLANTS- THE NEW ROUTE

Dental implants are an excellent option for replacing missing teeth. Traditional implants have a cylindrical or tapered geometry with threads along the screw length. The lack of proper congruency between the implant and the socket bone can eventually lead to implant failure due to stability loss and failure in osseointegration. To overcome this problem, novel approaches are being evaluated to manufacture customized root implants. This is expected to reduce the bone and soft-tissue trauma and promote a better primary stability. They do not require bone drilling, sinus lifting, bone augmentation or other traumatic procedures

Coherent anti-Stokes Raman spectroscopy of diamond

Experiments were performed to investigate Coherent Anti-Stokes Raman Scattering (CARS) in diamond. Aspects of this type of non-linear scattering are presented theoretically, and various experimental configurations were attempted in order to study them. These included the dependence of the CARS signal intensity on the intensities of the two exciting frequency-doubled Nd:YAG (pump) and dye (Stokes) lasers, the variation of the CARS signal polarization as a function of the lasers' polarization, and the dependence of the CARS signal intensity on the phase mismatch of the laser beams. The phase mismatch measurement confirmed the predicted sinc² nature of the CARS signal intensity, while· the polarization measurements provided new information on the ratio of the non-vanishing components of the cubic susceptibility x³ of diamond. The CARS signal intensity was found to change linearly with the dye laser intensity and quadratically with the Nd: Y AG laser intensity. The CARS signal was found at the predicted 1332 cm⁻¹ shift from the doubled Nd:YAG emission, and its linewidth of 1.2 cm⁻¹ is in agreement with the spontaneous Raman linewidth.The spectral data were fitted to a modified Voigt profile containing the non-resonant cubic susceptibility contribution, and this allowed us to establish the ratio of the resonant and non-resonant parts of x³. An attempt to generate Stimulated Raman Scattering in diamond was unsuccessful