Reproducibility of MRI-based white matter tract estimation using multi-fiber probabilistic tractography: effect of user-defined parameters and regions

Objective

There is a pressing need to assess user-dependent reproducibility of multi-fibre probabilistic tractography in order to encourage clinical implementation of these advanced and relevant approaches. The goal of this study was to evaluate both intrinsic and inter-user reproducibility of corticospinal tract estimation.

Materials and methods

Six clinical datasets including motor functional and diffusion MRI were used. Three users performed an independent tractography analysis following identical instructions. Dice indices were calculated to quantify the reproducibility of seed region, fMRI-based end region, and streamline maps.

Results

The inter-user reproducibility ranged 41–93%, 29–94%, and 50–92%, for seed regions, end regions, and streamline maps, respectively. Differences in streamline maps correlated with differences in seed and end regions. Good inter-user agreement in seed and end regions, yielded inter-user reproducibility close to the intrinsic reproducibility (92–97%) and in most cases higher than 80%.

Discussion

Uncertainties related to user-dependent decisions and the probabilistic nature of the analysis should be considered when interpreting probabilistic tractography data. The standardization of the methods used to define seed and end regions is a necessary step to improve the accuracy and robustness of multi-fiber probabilistic tractography in a clinical setting. Clinical users should choose a feasible compromise between reproducibility and analysis duration.

     

Hierarchical syntactic models for human activity recognition through mobility traces

Recognizing users’ daily life activities without disrupting their lifestyle is a key functionality to enable a broad variety of advanced services for     

Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Thermodynamic modeling of hydrogen refueling for heavy-duty fuel cell buses and comparison with aggregated real data

The foreseen uptake of hydrogen mobility is a fundamental step towards the decarbonization of the transport sector. Under such premises, both refueling infrastructure and vehicles should be deployed together with improved refueling protocols. Several studies focus on refueling the light-duty vehicles with 10 kg_H2 up to 700 bar, however less known effort is reported for refueling heavy-duty vehicles with 30–40 kg_H2 at 350 bar. The present study illustrates the application of a lumped model to a fuel cell bus tank-to-tank refueling event, tailored upon the real data acquired in the 3Emotion Project. The evolution of the main refueling quantities, such as pressure, temperature, and mass flow, are predicted dynamically throughout the refueling process, as a function of the operating parameters, within the safety limits imposed by SAE J2601/2 technical standard. The results show to refuel the vehicle tank from half to full capacity with an Average Pressure Ramp Rate (APRR) equal to 0.03 MPa/s are needed about 10 min. Furthermore, it is found that the effect of varying the initial vehicle tank pressure is more significant than changing the ambient temperature on the refueling performances. In conclusion, the analysis of the effect of different APRR, from 0.03 to 0.1 MPa/s, indicate that is possible to safely reduce the duration of half-to-full refueling by 62% increasing the APRR value from 0.03 to 0.08 MPa/s.     

2015年世博会卡里塔斯展馆及埃内尔展馆 意大利米兰

正Piuarch建筑师事务所负责设计了2015年米兰世博会埃内尔(意大利国家电力公司)展馆及卡里塔斯展馆。为了将客户想表达的含义与价值观更好地传达给观众,Piuarch选择了一种特殊的建筑语言来体现两个展馆的特点。埃内尔展馆沿东西大街而建,占地900平方米。设计体现出智能电网这一概念,传达出以智能科技优化世博会整体用电的理念。