MIDOT: A novel probe for monitoring high-current flat transmission lines

A novel inductive probe, termed MIDOT, was developed for monitoring high-current flat transmission lines. While being inexpensive the probe does not require calibration, is resistant to both shock waves and temperature variations, and it is easy to manufacture and mount. It generates strong output signals that are relatively easy to interpret and has a detection region limited to a pre-defined part of the transmission line. The theoretical background related to the MIDOT probes, together with their practical implementation in both preliminary experimentation and high-current tests, is also presented in the paper. The novel probe can be used to benchmark existing 2D numerical codes used in calculating the current distribution inside the conductors of a transmission line but can easily detect an early movement of a transmission line component. The probe can also find other applications, such as locating the position of a pulsed current flowing through a thin wire

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

MIDOT: A novel probe for monitoring high-current flat transmission lines

This paper was published in the journal Review of Scientific Instruments and the definitive published version is available at http://dx.doi.org/10.1063/1.4971246A novel inductive probe, termed MIDOT, was developed for monitoring high-current flat transmission lines. While being inexpensive the probe does not require calibration, is resistant to both shock waves and temperature variations, and it is easy to manufacture and mount. It generates strong output signals that are relatively easy to interpret and has a detection region limited to a pre-defined part of the transmission line. The theoretical background related to the MIDOT probes, together with their practical implementation in both preliminary experimentation and high-current tests, is also presented in the paper. The novel probe can be used to benchmark existing 2D numerical codes used in calculating the current distribution inside the conductors of a transmission line but can easily detect an early movement of a transmission line component. The probe can also find other applications, such as locating the position of a pulsed current flowing through a thin wire

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

BACKGROUND: Metastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1. METHODS: Gene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes. SIGNIFICANCE/CONCLUSION: This study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define "bona fide" Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions

A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance

Altering Chemosensitivity by Modulating Translation Elongation

BACKGROUND: The process of translation occurs at a nexus point downstream of a number of signal pathways and developmental processes. Modeling activation of the PTEN/AKT/mTOR pathway in the Emu-Myc mouse is a valuable tool to study tumor genotype/chemosensitivity relationships in vivo. In this model, blocking translation initiation with silvestrol, an inhibitor of the ribosome recruitment step has been showed to modulate the sensitivity of the tumors to the effect of standard chemotherapy. However, inhibitors of translation elongation have been tested as potential anti-cancer therapeutic agents in vitro, but have not been extensively tested in genetically well-defined mouse tumor models or for potential synergy with standard of care agents. METHODOLOGY/PRINCIPAL FINDINGS: Here, we chose four structurally different chemical inhibitors of translation elongation: homoharringtonine, bruceantin, didemnin B and cycloheximide, and tested their ability to alter the chemoresistance of Emu-myc lymphomas harbouring lesions in Pten, Tsc2, Bcl-2, or eIF4E. We show that in some genetic settings, translation elongation inhibitors are able to synergize with doxorubicin by reinstating an apoptotic program in tumor cells. We attribute this effect to a reduction in levels of pro-oncogenic or pro-survival proteins having short half-lives, like Mcl-1, cyclin D1 or c-Myc. Using lymphomas cells grown ex vivo we reproduced the synergy observed in mice between chemotherapy and elongation inhibition and show that this is reversed by blocking protein degradation with a proteasome inhibitor. CONCLUSION/SIGNIFICANCE: Our results indicate that depleting short-lived pro-survival factors by inhibiting their synthesis could achieve a therapeutic response in tumors harboring PTEN/AKT/mTOR pathway mutations

Construction and characterisation of AAA protease mutants of Synechocystis sp. strain PCC 6803

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN030928 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Abordul percutanat renal în tratamentul calculului coraliform

Obiectivul lucrării În lucrarea de față s-a încercat o analiză retrospectivă a experienţei noastre în tratamentul percutanat al calculului coraliform în perioada 1 iulie 1997 - 30 iunie 2002 (considerând că primii 2 ani de utilizare a metodei au reprezentat curba de învăţare). Material şi metodă În ultimii cinci ani, din 354 pacienţi ce au impus nefrolitotomie percutanată (NLP) jumătate au fost pentru calculi coraliformi (180 cazuri). Clasificarea Moares-O'Boyle a fost utilizată pentru repartiția cazurilor pe tip de calcul: tip A - 34 cazuri (18,8%), В - 25 cazuri (13,8%), C - 41 cazuri (22,7%), D - 8 cazuri (4,4%), E - 69 cazuri (38,3%), F - 3 cazuri (1,6%). Dintre factorii favorizanti sau agravanţi întâlniţi menţionăm: rinichi contralateral afectat - 15 cazuri (8,3%), lombă cicatriceală - 9 cazuri (5%), insuficientă renală cronică - 8 cazuri (4,4%), sepsis - 7 cazuri (3,8% ),rinichi unic (2,7%). Abordul percutanat renal a fost realizat utilizând ghidaj fluoroscopic şi ecografic. în 8 cazuri au fost necesare nefrostomii percutanate de drenaj, premergătoare intervenţiei propriu-zise. Majoritatea pacienţilor (116 - 64,5%) au necesitat un singur timp operator iar 64 pacienţi (35,5%) au impus 2-3 şedinţe operatorii. 164 pacienţi (91%) au fost rezolvaţi utilizându-se un singur traiect de nefrostomie şi numai 16 cazuri (9%) necesitând două traiecte. A fost utilizată atât litotritia balistică (108 cazuri) cît şi cea ultrasonică (72 cazuri). Dintre complicaţiile majore menţionăm: 1 deces prin şoc hemoragie şi fibrinoliză (chiar după nefrectomia de necesitate) şi 1 caz la care s-a practicat tardiv nefrectomie (pentru hidronefroză subcapsulară). Rezultate În urma analizei cazurilor reiese că rata globală a restantelor a fost de 29% din cazuri, crescută în cazul utilizării NLP ca monoterapie (71% din cazuri "stone-free»), în cazul asocierii cu litotritia extracorporeală rata de “stone-free» a crescut la 87% (157 cazuri). Concluzii Nefrolitotomia percutanată reprezintă metoda terapeutică de electie în calculul coraliform iar asocierea cu litotriția extracorporeală conferă rezultate superioare chirurgiei deschise

Molecular biomarkers in clinical development: What could we learn from the clinical trial registry?

Aim: Objective of this research is to assess whether the trend of stratified medicine widely discussed in scientific literature is translated into real clinical trials registered in ClinicalTrials.gov. Methods: By semi-automatic screening of over 150,000 trials, we filtered trials with stratified biomarker to analyze their therapeutic focus, major drivers and elucidated the impact of stratified biomarker programs on trial duration and completion. Results: >5% of trials are using molecular biomarker for stratification; duration of such trials is longer. 21% of them are done in late stages and Oncology is the major focus. Conclusion: Trials with stratified biomarker in drug development has quadrupled in last decade but represents a small part of all interventional trials reflecting multiple co-developmental challenges of therapeutic compounds and companion diagnostics