Non-destructive testing techniques for the observation of healing effects in cementitious materials: an introduction

To develop an appropriate method of self-healing for cementitious materials including the right composition and amount of suitable healing agents it is required to investigate the healing efficiency for certain material mixtures. While some researchers evaluate the regain in compressive strength by means of destructive load tests, this method is obviously second best in particular for field applications. In a large EU project the best candidates among the non-destructive testing methods are investigated to be applied in small and large laboratory experiments as well as at real structures in-situ. The paper is giving an introduction to these techniques and addresses also issues of structural health monitoring used for example to monitor the healing effects on a long term basis and to assess the condition of the structure, where self-healing techniques are applied

User's guide for the Nimbus 7 Scanning Multichannel Microwave Radiometer (SMMR) CELL-ALL tape

The SMMR instrument onboard the Nimbus-7 satellite has been in operation since October 1978. It provided global coverage of passive microwave observations at 6.6, 10.7, 18, 21, and 37 GHz. The oberved brightness temperature can be used to retrieve geophysical parameters, principally sea surface temperature, atmospheric water vapor and liquid water content over oceans, sea ice concentration, and snow cover over land. The SMME CELL-ALL Tape contains earth-located calibrated brightness temperature data which have been appropriately binned into cells of various grid sizes, allowing intercomparisons of observations made at different frequencies (with corresponding different footprint sizes). This user's guide describes the operation of the instrument, the flow of the data processing the calibration procedure, and the characteristics of the calibrated brightness temperatures and how they are binned. Detailed tape specifications and lists of available data are also provided

Small molecule inhibition of CBP/catenin interactions eliminates drug resistant clones in acute lymphoblastic leukemia

Drug resistance in acute lymphoblastic leukemia (ALL) remains a major problem warranting new treatment strategies. Wnt/catenin signaling is critical for the self-renewal of normal hematopoietic progenitor cells. Deregulated Wnt signaling is evident in chronic and acute myeloid leukemia, however little is known about ALL. Differential interaction of catenin with either the Kat3 coactivator CREBBP (CBP) or the highly homologous EP300 (p300) is critical to determine divergent cellular responses and provides a rationale for the regulation of both proliferation and differentiation by the Wnt signaling pathway. Usage of the coactivator CBP by catenin leads to transcriptional activation of cassettes of genes that are involved in maintenance of progenitor cell self-renewal. However, the use of the coactivator p300, leads to activation of genes involved in the initiation of differentiation. ICG-001 is a novel small molecule modulator of Wnt/catenin signaling, which specifically binds to the N-terminus of CBP and not p300, within amino acids 1–110, thereby disrupting the interaction between CBP and catenin. Here, we report that selective disruption of the CBP/β- and γ-catenin interactions using ICG-001 leads to differentiation of pre-B ALL cells and loss of self-renewal capacity. Survivin, an inhibitor-of-apoptosis protein, was also downregulated in primary ALL after treatment with ICG-001. Using ChIP assay, we demonstrate occupancy by CBP of the survivin promoter, which is decreased by ICG-001 in primary ALL. CBP-mutations have been recently identified in a significant percentage of ALL patients, however, almost all of the identified mutations reported occur C-terminal to the binding site for ICG-001. Importantly, ICG-001, regardless of CBP mutational status and chromosomal aberration, leads to eradication of drug-resistant primary leukemia in combination with conventional therapy in vitro and significantly prolongs the survival of NOD/SCID mice engrafted with primary ALL. Therefore, specifically inhibiting CBP/catenin transcription represents a novel approach to overcome relapse in ALL

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

THE PATENTED DRUGS UTILIZATION: A STUDY AT NGUYEN DINH CHIEU HOSPITAL IN BEN TRE PROVINCE FROM 2011 TO 2017

Objective: With their new and efficacious active ingredients, patented drugs have important roles in offering high-quality healthcare. However, huge cost-related barriers in accessing patented drugs along with the availability of low-cost bioequivalent generics have great impact on drugs policy in Vietnam. To understand situation of patented drugs utilization at hospitals for a certain period, this pilot study was conducted at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province. Methods: The cross-sectional descriptive study was conducted on the retrospective data of all patented drugs used at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province from 2011-2017. Characteristics of drugs utilization were described by frequency and percentage of drugs quantities and costs. Criteria for the description were as follows: active ingredient, route of administration, therapeutic class and manufacturing country. Data were extracted from the hospital information system and were processed by R software. Results: From 2011 to 2017, there were 212 patented drugs used which related to 145 active ingredients and 20 therapeutic classes. 88% were single active ingredient drugs and 49% were oral drugs. Antimicrobial and cardiovascular drugs represented the largest number of drugs and the highest cost. 79% of patented drugs were manufactured by companies in Europe and the majority came from France and Germany. Conclusion: This study provided initial information about the utilization of patented drugs during a long period of time at a Vietnamese hospital. The understanding gained will aid medical managers in assessment and adjustment of the drugs list, thus, optimizing the hospital budget and the equity in access to drugs within communities

Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing

An overview of using small punch testing for mechanical characterization of MCrAlY bond coats

Considerable work has been carried out on overlay bond coats in the past several decades because of its excellent oxidation resistance and good adhesion between the top coat and superalloy substrate in the thermal barrier coating systems. Previous studies mainly focus on oxidation and diffusion behavior of these coatings. However, the mechanical behavior and the dominant fracture and deformation mechanisms of the overlay bond coats at different temperatures are still under investigation. Direct comparison between individual studies has not yet been achieved due to the fragmentary data on deposition processes, microstructure and, more apparently, the difficulty in accurately measuring the mechanical properties of thin coatings. One of the miniaturized specimen testing methods, small punch testing, appears to have the potential to provide such mechanical property measurements for thin coatings. The purpose of this paper is to give an overview of using small punch testing to evaluate material properties and to summarize the available mechanical properties that include the ductile-to-brittle transition and creep of MCrAlY bond coat alloys, in an attempt to understand the mechanical behavior of MCrAlY coatings over a broad temperature range

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton

Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to regulate cell polarity and directional cell migration

The LRRK2 signalling system

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review