Multilevel Modular Mesocrystalline Organization in Red Coral

International audienceBiominerals can achieve complex shapes as aggregates of crystalline building blocks. In the red coral skeleton, we observe that these building blocks are arranged into eight hierarchical levels of similarly (but not identically) oriented modules. The modules in each hierarchical level assemble into larger units that comprise the next higher level of the hierarchy, and consist themselves of smaller, oriented modules. EBSD and TEM studies show that the degree of crystallographic misorientation between the building blocks decreases with decreasing module size. We observe this organization down to a few nm. Thus, the transition from imperfect crystallographic order at mm scale to nearly perfect single crystalline domains at nm scale is progressive. The concept of 'mesocrystal' involves the three-dimensional crystallographic organization of nanoparticles into a highly ordered mesostructure. We add to this concept the notion of 'multilevel modularity'. This modularity has potential implications for the origin of complex biomineral shapes in nature. A multilevel modular organization with small intermodular misorientations combines a simple construction scheme, ruled by crystallographic laws, with the possibility of complex shapes. If the observations we have made on red coral extend to other biominerals, long-range crystallographic order and interfaces at all scales may be key to how some biominerals achieve complex shapes adapted to the environment in which they grow

Wetting and bonding characteristics of selected liquid-metals with a high power diode laser treated alumina bioceramic

Changes in the wettability characteristics of an alumina bioceramic occasioned by high power diode laser (HPDL) surface treatment were apparent from the observed reduction in the contact angle. Such changes were due to the HPDL bringing about reductions the surface roughness, increases in the surface O2 content and increases in the polar component of the surface energy. Additionally, HPDL treatment of the alumina bioceramic surface was found to effect an improvement in the bonding characteristics by increasing the work of adhesion. An electronic approach was used to elucidate the bonding characteristics of the alumina bioceramic before and after HPDL treatment. It is postulated that HPDL induced changes to the alumina bioceramic produced a surface with a reduced bandgap energy which consequently increased the work of adhesion by increasing the electron transfer at the metal/oxide interface and thus the metal-oxide interactions. Furthermore, it is suggested that the increase in the work of adhesion of the alumina bioceramic after HPDL treatment was due to a correlation existing between the wettability and ionicity of the alumina bioceramic; for it is believed that the HPDL treated surface is less ionic in nature than the untreated surface and therefore exhibits better wettability characteristics

Encoding conformance checking artefacts in SAT

Conformance checking strongly relies on the computation of artefacts, which enable reasoning on the relation between observed and modeled behavior. This paper shows how important conformance artefacts like alignments, anti-alignments or even multi-alignments, defined over the edit distance, can be computed by encoding the problem as a SAT instance. From a general perspective, the work advocates for a unified family of techniques that can compute conformance artefacts in the same way. The prototype implementation of the techniques presented in this paper show capabilities for dealing with some of the current benchmarks, and potential for the near future when optimizations similar to the ones in the literature are incorporated.Peer ReviewedPostprint (author's final draft

Encoding conformance checking artefacts in SAT

Conformance checking strongly relies on the computation of artefacts, which enable reasoning on the relation between observed and modeled behavior. This paper shows how important conformance artefacts like alignments, anti-alignments or even multi-alignments, defined over the edit distance, can be computed by encoding the problem as a SAT instance. From a general perspective, the work advocates for a unified family of techniques that can compute conformance artefacts in the same way. The prototype implementation of the techniques presented in this paper show capabilities for dealing with some of the current benchmarks, and potential for the near future when optimizations similar to the ones in the literature are incorporated.Peer ReviewedPostprint (author's final draft

MTSS1 is a critical epigenetically regulated tumor suppressor in CML

Chronic myeloid leukemia (CML) is driven by malignant stem cells that can persist despite therapy. We have identified Metastasis suppressor 1 (Mtss1/MIM) to be downregulated in hematopoietic stem and progenitor cells from leukemic transgenic SCLtTA/Bcr-Abl mice and in patients with CML at diagnosis, and Mtss1 was restored when patients achieved complete remission. Forced expression of Mtss1 decreased clonogenic capacity and motility of murine myeloid progenitor cells and reduced tumor growth. Viral transduction of Mtss1 into lineage depleted SCLtTA/Bcr-Abl bone marrow cells decreased leukemic cell burden in recipients, and leukemogenesis was reduced upon injection of Mtss1 overexpressing murine myeloid 32D cells. Tyrosine kinase inhibitor (TKI) therapy and reversion of Bcr-Abl expression increased Mtss1 expression but failed to restore it to control levels. CML patient samples revealed higher DNA methylation of specific Mtss1 promoter CpG sites that contain binding sites for Kaiso and Rest transcription factors. In summary, we identified a novel tumor suppressor in CML stem cells that is downregulated by both Bcr-Abl kinase-dependent and -independent mechanisms. Restored Mtss1 expression markedly inhibits primitive leukemic cell biology in vivo, providing a therapeutic rationale for the Bcr-Abl-Mtss1 axis to target TKI resistant CML stem cells in patients

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms.

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis

Microscopic View on Short-Range Wetting at the Free Surface of the Binary Metallic Liquid Gallium-Bismuth: An X-ray Reflectivity and Square Gradient Theory Study

We present an x-ray reflectivity study of wetting at the free surface of the binary liquid metal gallium-bismuth (Ga-Bi) in the region where the bulk phase separates into Bi-rich and Ga-rich liquid phases. The measurements reveal the evolution of the microscopic structure of wetting films of the Bi-rich, low-surface-tension phase along different paths in the bulk phase diagram. A balance between the surface potential preferring the Bi-rich phase and the gravitational potential which favors the Ga-rich phase at the surface pins the interface of the two demixed liquid metallic phases close to the free surface. This enables us to resolve it on an Angstrom level and to apply a mean-field, square gradient model extended by thermally activated capillary waves as dominant thermal fluctuations. The sole free parameter of the gradient model, i.e. the so-called influence parameter, $\kappa$, is determined from our measurements. Relying on a calculation of the liquid/liquid interfacial tension that makes it possible to distinguish between intrinsic and capillary wave contributions to the interfacial structure we estimate that fluctuations affect the observed short-range, complete wetting phenomena only marginally. A critical wetting transition that should be sensitive to thermal fluctuations seems to be absent in this binary metallic alloy.Comment: RevTex4, twocolumn, 15 pages, 10 figure

Generalized alignment-based trace clustering of process behavior

Process mining techniques use event logs containing real process executions in order to mine, align and extend process models. The partition of an event log into trace variants facilitates the understanding and analysis of traces, so it is a common pre-processing in process mining environments. Trace clustering automates this partition; traditionally it has been applied without taking into consideration the availability of a process model. In this paper we extend our previous work on process model based trace clustering, by allowing cluster centroids to have a complex structure, that can range from a partial order, down to a subnet of the initial process model. This way, the new clustering framework presented in this paper is able to cluster together traces that are distant only due to concurrency or loop constructs in process models. We show the complexity analysis of the different instantiations of the trace clustering framework, and have implemented it in a prototype tool that has been tested on different datasets.Peer ReviewedPostprint (author's final draft