Beyond graph neural networks with lifted relational neural networks

Machine Learning - We introduce a declarative differentiable programming framework, based on the language of Lifted Relational Neural Networks, where small parameterized logic programs are used to...     

Granulation Tissue Enhanced with Aspirin and Omega-3 PUFAs as a Local Adjunct to the Surgical Treatment of Periodontitis

The topical application of aspirin and omega-3 polyunsaturated fatty acids (PUFAs) may trigger the resolution of inflammation by inducing the biosynthesis of pro-resolvers such as lipoxins and resolvins while also avoiding the side effects of systemic aspirin intake. This study assessed the effect of enhanced granulation tissue (EGT) on periodontal tissue regeneration through the local application of aspirin and omega-3 PUFAs directly to granulation tissue (GT) during periodontal surgery. This randomized controlled experiment assesses 38 pockets in 19 patients. In every patient, two similar intrabony periodontal defects are treated with an open flap debridement, one with EGT (GT extracted, enhanced with aspirin and omega-3 PUFAs, and replaced) and the other with standard GT removal. Clinical attachment level (CAL) and probing pocket depth (PPD) are assessed at baseline and 2 and 6 months after surgery. The experimental protocol (EGT) results in a greater CAL gain as compared to that in the controls at 6 months (p < 0.05), while PPD reduction is not affected. The retained GT does not compromise healing. EGT is proposed as a promising, inexpensive, and simple method that may improve the outcome of periodontal regenerative treatment. However, the described protocol requires optimization and further assessment. Practical Applications : The biosynthesis of mediators including resolvins and lipoxins triggered by aspirin and omega-3 PUFAs promote the resolution of inflammation, eventually leading to faster regeneration of inflamed tissues. While granulation tissue is a necessary component in wound healing, enhancing granulation tissue with aspirin and omega-3 PUFAs results in CAL gain in the surgical treatment of periodontal defects. Retained granulation tissue does not compromise periodontal healing. The EGT strategy is an inexpensive and simple method that may improve the clinical outcomes of regenerative periodontal procedures.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and −318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the −1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.     

In Situ Generation of n-Type Dopants by Thermal Decarboxylation

Molecular doping is a powerful and increasingly popular approach toward enhancing electronic properties of organic semiconductors (OSCs) past their intrinsic limits. The development of n-type dopants has been hampered, however, by their poor stability and high air-reactivity, a consequence of their generally electron rich nature. Here, the use of air-stable carboxylated dopant precursors is reported to overcome this challenge. Active dopants are readily generated in solution by thermal decarboxylation and applied in n-type organic field-effect transistors (OFETs). Both 1,3-dimethylimidazolium-2-carboxylate (CO₂-DMI) and novel dopant 1,3-dimethylbenzimidazolium-2-carboxylate (CO₂-DMBI) are applied to n-type OFETs employing well-known organic semiconductors (OSCs) P(NDI2OD-T2), PCBM, and O-IDTBR. Successful improvement of performance in all devices demonstrates the versatility of the dopants across a variety of OSCs. Experimental and computational studies indicate that electron transfer from the dopant to the host OSC is preceded by decarboxylation of the precursor, followed by dimerization to form the active dopant species. Transistor studies highlight CO₂-DMBI as the most effective dopant, improving electron mobility by up to one order of magnitude, while CO₂-DMI holds the advantage of commercial availability.     

Assessing and interpreting personality change and continuity in patients treated for major depression.

Structural, mean- and individual-level, differential, and ipsative personality continuity were examined in 599 patients treated for major depression assigned to 1 of 6 forms of a 6-month pharmaco-psychotherapy program. Covariation among traits from the Five Factor model remained invariant across treatment, and patients described themselves as slightly more extraverted, open to experience, agreeable and conscientious, and substantially more emotional stable after treatment. Trait changes were only to a small extent explained by changes in depression severity. There was evidence for differential, individual-level, and ipsative stability, with stable personality profiles in terms of shape and to a lesser extent in terms of scatter and elevation. Traits remain relatively stable, except for emotional stability, despite the depressive state and the psychopharmacological interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Encoding Information on the Excited State of a Molecular Spin Chain

The quantum states of nano-objects can drive electrical transport properties across lateral and local-probe junctions. This raises the prospect, in a solid-state device, of electrically encoding information at the quantum level using spin-flip excitations between electron spins. However, this electronic state has no defined magnetic orientation and is short-lived. Using a novel vertical nanojunction process, these limitations are overcome and this steady-state capability is experimentally demonstrated in solid-state spintronic devices. The excited quantum state of a spin chain formed by Co phthalocyanine molecules coupled to a ferromagnetic electrode constitutes a distinct magnetic unit endowed with a coercive field. This generates a specific steady-state magnetoresistance trace that is tied to the spin-flip conductance channel, and is opposite in sign to the ground state magnetoresistance term, as expected from spin excitation transition rules. The experimental 5.9 meV thermal energy barrier between the ground and excited spin states is confirmed by density functional theory, in line with macrospin phenomenological modeling of magnetotransport results. This low-voltage control over a spin chain's quantum state and spintronic contribution lay a path for transmitting spin wave-encoded information across molecular layers in devices. It should also stimulate quantum prospects for the antiferromagnetic spintronics and oxides electronics communities.     

Heavy metal mobility in intertidal sediments of the Scheldt estuary: Field monitoring

The current paper aims to check whether the factors affecting metal mobility in intertidal sediments and floodplain soils of the river Scheldt, as identified under controlled greenhouse conditions in previous studies, also play a similar role under variable field conditions. Moreover, we aimed to assess the importance of these factors as a function of sampling time and depth, with respect to the natural variations in water table levels. This field monitoring revealed that the mobility of metals in intertidal sediments of the Scheldt estuary indeed are affected by factors which were identified to affect the metal fate in the upper sediment layer in previous greenhouse experiments. However, the effects were often less pronounced under field conditions. This can be attributed to the lower sampling resolution, the occurrence of interactions between factors, the disturbance of microbial communities during setup of greenhouse experiments and the more moderate environmental conditions in the field, affecting microbial and enzymatic activities. At most of the sampled wetlands, the level of the water table fluctuated only slightly during fall, winter and spring, whereas it decreased substantially during summer, especially at the sites with more sandy sediments. The highest sulphide concentrations were found at the sites where the water table level never decreased considerably. These sulphides primarily suppress the availability of Cd, Cu, Ni and Zn. Organic complexation resulted in the mobilisation of Cu, Ni and Cr. The concentrations of Cd, Ni and Zn in the pore water were affected by Fe/Mn oxide reduction, whereas Cd and Zn concentrations appeared to be also affected by the salinity.     

Extraction of Distinguished Hyperbolic Trajectories for 2D Time-Dependent Vector Field Topology

This paper does two main contributions to 2D time-dependent vector field topology. First, we present a technique for robust, accurate, and efficient extraction of distinguished hyperbolic trajectories (DHT), the generative structures of 2D time-dependent vector field topology. It is based on refinement of initial candidate curves. In contrast to previous approaches, it is robust because the refinement converges for reasonably close initial candidates, it is accurate due to its adaptive scheme, and it is efficient due to its high convergence speed. Second, we provide a detailed evaluation and discussion of previous approaches for the extraction of DHTs and time-dependent vector field topology in general. We demonstrate the utility of our approach using analytical flows, as well as data from computational fluid dynamics.