Aryloxy Triester Phosphoramidates as Phosphoserine Prodrugs: A Proof of Concept Study

The specific targeting of protein-protein interactions by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinder its uptake into cells. To address these issues, we herein report the synthesis of phosphoserine aryloxy triester phosphoramidates as phosphoserine prodrugs that are enzymatically metabolized to release phosphoserine. This phosphoserine-masking approach was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and the generated prodrugs exhibited improved pharmacological activity. Collectively, this provided a proof of concept that the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups is a viable intracellular delivery system for phosphoserine-containing molecules. Ultimately, this will facilitate the discovery of phosphoserine-containing small-molecule therapeutics.     

Effects of local metakaolin addition on rheological and mechanical performance of self-compacting limestone cement concrete

Various mineral additions are used in the manufacture of self-compacting concrete (SCC) to reduce the cement content and hence the CO₂ emissions and also to enhance the performance of concrete. In this paper, the results of fresh and hardened properties of self-compacting limestone cement mortar (SCLCM) and concrete (SCLCC) with metakaolin (MK) as cement replacement are reported. SCLCM properties investigated include spread flow, V-funnel flow time, yield stress, plastic viscosity and heat evolution. SCLCC fresh properties include slump flow, V-funnel flow time, J-Ring, L-Box and sieve segregation. Compressive strength of the hardened SCLCC was measured at the ages of 1, 3, 7, 28, 90, and 180?days. Moreover, water porosity, water absorption by capillarity and dynamic modulus of elasticity (E_d) tests were conducted. Test results indicated that the produced MK is of sufficient pozzolanic activity and contributes to improve the performances of concrete in particular at later stages. The addition of MK to SCLCM mixes exhibits lower heat evolution, lower yield stress, higher plastic viscosity and higher V-funnel flow time. The addition of MK to SCLCC mixes improves the rheological properties (flowability, passing ability and segregation resistance) as well as the mechanical and durability performance.     

QuicK-means: accelerating inference for K-means by learning fast transforms

Machine Learning - K-means—and the celebrated Lloyd’s algorithm—is more than the clustering method it was originally designed to be. It has indeed proven pivotal to help increase...     

Repair of congenital pulmonary incompetence by bicuspidization of the pulmonary valve

We report the successful repair of pulmonary incompetence in an adult due to the congenital absence of the posterior leaflet of the pulmonary valve. The repair consisted of bicuspidization of the pulmonary valve, which achieved competence and eliminated the symptoms and echocardiographic manifestations of right ventricular overload while preserving the native valve.     

Correlation Between the Pitting Potential Evolution and $$\varvec\sigma$$ Phase Precipitation Kinetics in the 2205 Duplex Stainless Steel

The aim of this work is to correlate the pitting potential (E_pit) evolution with the kinetics of σ phase precipitation in the 2205 duplex stainless steel aged at 850 °C after solution treatment at 1150 °C. The potentiodynamic polarization curves indicate a reduction of the pitting corrosion resistance with the aging time, which is revealed by a decrease in the E_pit values from 0.65 to 0.40 V_SCE. Thus, E_pit values are used to determine the kinetics parameters of the σ phase precipitation. The experimental transformed fraction agrees well with the one calculated by using the modified Kolmogorov–Johnson–Mehl–Avrami equation with an impingement parameter c?=?0.6.     

Human TRMT112-Methyltransferase Network Consists of Seven Partners Interacting with a Common Co-Factor

Methylation is an essential epigenetic modification mainly catalysed by S-Adenosyl methionine-dependent methyltransferases (MTases). Several MTases require a cofactor for their metabolic stability and enzymatic activity. TRMT112 is a small evolutionary conserved protein that acts as a co-factor and activator for different MTases involved in rRNA, tRNA and protein methylation. Using a SILAC screen, we pulled down seven methyltransferases—N6AMT1, WBSCR22, METTL5, ALKBH8, THUMPD2, THUMPD3 and TRMT11—as interaction partners of TRMT112. We showed that TRMT112 stabilises all seven MTases in cells. TRMT112 and MTases exhibit a strong mutual feedback loop when expressed together in cells. TRMT112 interacts with its partners in a similar way; however, single amino acid mutations on the surface of TRMT112 reveal several differences as well. In summary, mammalian TRMT112 can be considered as a central “hub” protein that regulates the activity of at least seven methyltransferases.     

Design and numerical analysis of interdigitated radiating-strips electrode for uniform 3D dielectrophoretic patterning of liver cells

Microsystem Technologies - This paper presents the design and numerical analysis of a new three-dimensional (3D) electrode having a non-uniform electric field gradient for dielectrophoretic...     

Ethnic differences in housing in post-Soviet Tartu,Estonia

Social and ethnic stratification has changed significantly in the former Soviet space since 1991. This research analyses the evolution of inherited ethnic differences in housing during two post-Soviet decades in Tartu, Estonia. The results suggest that ethnic inequalities in dwelling type as well as in housing size per person decreased between 1989 and 2008. More minorities now occupy single-family houses than at the end of the Soviet period. Access to modern facilities within dwelling units, however, is still higher among the minority population. We conclude that inherited ethnic differences in housing conditions were pronounced and, despite evidence of decreasing housing inequalities, subsequent changes have been too modest to overcome inherited patterns of housing segmentation from the Soviet period.     

Geostatistics applied to mine waste characterization at Leadville,Colorado, USA

ABSTRACT

This paper will describe the process of identifying lead contaminated soil areas exceeding a certain threshold at a historical mining district using geostatistical tools. For this purpose, lead concentration samples coming from Leadville County, Colorado were chosen as the data sets to be examined. In order to check integrity of data files, posting of the data values at sample locations is performed on each of the four data sets available. Statistical analysis is used for identifying possible different populations within the study area Based on the statistical results, the data sets were subdivided into four different populations as they relate to residential domains. More detail geostatistical analysis of data set representing the City of Leadville domain (CL) is performed Variogram analysis is used to characterize spatial variability on the data sets within CL limits. Generation of variograms for such data sets and identification of their parameters such as sill, nugget, range, and anisotropy ratios is performed. Once these parameters are identified, variogram modeling is accomplished. A significant spatial correlation is found within CL boundaries and two geostatistical estimation techniques named ordinary kriging and indicator kriging are applied to determine level of contamination at unsampled locations exceeding 3500 PPM threshold. Such techniques are tested by cross validation in order to check possible overestimation bias over 3500 PPM threshold. Indicator Kriging was found to be the best estimator which provided the minimum overestimation bias of areas of contamination exceeding 3500 PPM threshold compared with ordinary kriging.