Development problem analysis of correlation leak detector's software

In the article, the practical application and the structure of the correlation leak detectors' software is studied and the task of its designing is analyzed. In the first part of the research paper, the expediency of the facilities development of correlation leak detectors for the following operating efficiency of public utilities exploitation is shown. The analysis of the functional structure of correlation leak detectors is conducted and its program software tasks are defined. In the second part of the research paper some development steps of the software package - requirement forming, program structure definition and software concept creation - are examined in the context of the usage experience of the hardware-software prototype of correlation leak detector

siRNA Targeted to p53 Attenuates Ischemic and Cisplatin-Induced Acute Kidney Injury

Proximal tubule cells (PTCs), which are the primary site of kidney injury associated with ischemia or nephrotoxicity, are the site of oligonucleotide reabsorption within the kidney. We exploited this property to test the efficacy of siRNA targeted to p53, a pivotal protein in the apoptotic pathway, to prevent kidney injury. Naked synthetic siRNA to p53 injected intravenously 4 h after ischemic injury maximally protected both PTCs and kidney function. PTCs were the primary site for siRNA uptake within the kidney and body. Following glomerular filtration, endocytic uptake of Cy3-siRNA by PTCs was rapid and extensive, and significantly reduced ischemia-induced p53 upregulation. The duration of the siRNA effect in PTCs was 24 to 48 h, determined by levels of p53 mRNA and protein expression. Both Cy3 fluorescence and in situ hybridization of siRNA corroborated a short t½ for siRNA. The extent of renoprotection, decrease in cellular p53 and attenuation of p53-mediated apoptosis by siRNA were dose- and time-dependent. Analysis of renal histology and apoptosis revealed improved injury scores in both cortical and corticomedullary regions. siRNA to p53 was also effective in a model of cisplatin-induced kidney injury. Taken together, these data indicate that rapid delivery of siRNA to proximal tubule cells follows intravenous administration. Targeting siRNA to p53 leads to a dose-dependent attenuation of apoptotic signaling, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury

Baryon Budget of the Hot Circumgalactic Medium of Massive Spiral Galaxies

The baryon content around local galaxies is observed to be much less than is needed in Big Bang nucleosynthesis. Simulations indicate that a significant fraction of these "missing baryons" may be stored in a hot tenuous circumgalactic medium (CGM) around massive galaxies extending to or even beyond the virial radius of their dark matter halos. Previous observations in X-ray and Sunyaev–Zel'dovich (SZ) signals claimed that ~(1–50)% of the expected baryons are stored in a hot CGM within the virial radius. The large scatter is mainly caused by the very uncertain extrapolation of the hot gas density profile based on the detection in a small radial range (typically within 10%–20% of the virial radius). Here, we report stacking X-ray observations of six local isolated massive spiral galaxies from the CGM-MASS sample. We find that the mean density profile can be characterized by a single power law out to a galactocentric radius of ≈200 kpc (or ≈130 kpc above the 1σ background uncertainty), about half the virial radius of the dark matter halo. We can now estimate that the hot CGM within the virial radius accounts for (8 ± 4)% of the baryonic mass expected for the halos. Including the stars, the baryon fraction is (27 ± 16)%, or (39 ± 20)% by assuming a flattened density profile at r gsim 130 kpc. We conclude that the hot baryons within the virial radius of massive galaxy halos are insufficient to explain the "missing baryons.

Development of a Novel Virtual Screening Cascade Protocol to Identify Potential Trypanothione Reductase Inhibitors

The implementation of a novel sequential computational approach that can be used effectively for virtual screening and identification of prospective ligands that bind to trypanothione reductase (TryR) is reported. The multistep strategy combines a ligand-based virtual screening for building an enriched library of small molecules with a docking protocol (AutoDock, X-Score) for screening against the TryR target. Compounds were ranked by an exhaustive conformational consensus scoring approach that employs a rank-by-rank strategy by combining both scoring functions. Analysis of the predicted ligand-protein interactions highlights the role of bulky quaternary amine moieties for binding affinity. The scaffold hopping (SHOP) process derived from this computational approach allowed the identification of several chemotypes, not previously reported as antiprotozoal agents, which includes dibenzothiepine, dibenzooxathiepine, dibenzodithiepine, and polycyclic cationic structures like thiaazatetracyclo-nonadeca-hexaen-3-ium. Assays measuring the inhibiting effect of these compounds on T. cruzi and T. brucei TryR confirm their potential for further rational optimization