Determination of maximum tolerated dose and toxicity of Inauhzin in mice

AbstractReactivating the tumor suppressor p53 offers an attractive strategy for developing cancer therapy. We recently identified Inauhzin (INZ) as a novel non-genotoxic p53-activating compound. To develop INZ into a clinically applicable anticancer drug, we have initiated preclinical toxicity studies. Here, we report our study on determining the maximum tolerated dose (MTD) of INZ analog, Inauhzin-C (INZ (C)), following intraperitoneal (i.p.) administration (Phase A) and its toxicity following i.p. administration over a period of 5-day dosing plus 2-day recovery (Phase B) in CD-1 mice. The Phase A study showed that the MTD of INZ (C) is 200mg/kg for female and 250mg/kg for male, respectively. The Phase B study showed that the administration of INZ (C) via 5-day consecutive i.p. injection is tolerated by female CD-1 mice at all dose levels tested from 50mg/kg to 120mg/kg without significant changes in biochemical and pathological parameters in the animals. Together, these results indicate that our previously determined effective dose of INZ at 30–60mg/kg via i.p. is quite safe to mice, and imply that this compound have the features worthy for further development into a clinically applicable drug

Removal of phenol using sulphate radicals activated by natural zeolite-supported cobalt catalysts

Two Co oxide catalysts supported on natural zeolites from Indonesia (INZ) and Australia (ANZ) were prepared and used to activate peroxymonosulphate for degradation of aqueous phenol. The two catalysts were characterized by several techniques such as X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy (EDS) and N2 adsorption. It was found that Co/INZ and Co/ANZ are effective in activation of peroxymonosulphate to produce sulphate radicals for phenol degradation. Co/INZ and Co/ANZ could remove phenol up to 100 and 70 %, respectively, at the conditions of 25 ppm phenol (500 mL), 0.2 g catalyst, 1 g oxone and 25 °C. Several parameters such as amount of catalyst loading, phenol concentration, oxidant concentration and temperature were found to be the key factors influencing phenol degradation. A pseudo first order would fit to phenol degradation kinetics, and the activation energies on Co/INZ and Co/ANZ were obtained as 52.4 and 61.3 kJ/mol,respectively

Realization of broadband index-near-zero modes in nonreciprocal magneto-optical heterostructures

Epsilon-near-zero (ENZ) metamaterial with the relative permittivity approaching zero has been a hot research subject in the past decades. The wave in the ENZ region has infinite phase velocity ($v=1/\sqrt{\varepsilon\mu}$), whereas it cannot efficiently travel into the other devices or air due to the impedance mismatch or near-zero group velocity. In this paper, we demonstrate that the tunable index-near-zero (INZ) modes with vanishing wavenumbers ($k=0$) and nonzero group velocities ($v_\mathrm{g} \neq 0$) can be achieved in nonreciprocal magneto-optical systems. This kind of INZ modes has been experimentally demonstrated in the photonic crystals at Dirac point frequencies and that impedance-matching effect has been observed as well. Our theoretical analysis reveals that the INZ modes exhibit tunability when changing the parameter of the one-way (nonreciprocal) waveguides. Moreover, owing to the zero-phase-shift characteristic and decreasing $v_\mathrm{g}$ of the INZ modes, several perfect optical buffers (POBs) are proposed in the microwave and terahertz regimes. The theoretical results are further verified by the numerical simulations performed by the finite element method. Our findings may open the new avenues for research in the areas of ultra -strong or -fast nonlinearity, perfect cloaking, high-resolution holographic imaging and wireless communications

The role of IMP dehydrogenase 2 in Inauhzin-induced ribosomal stress

The ‘ribosomal stress (RS)-p53 pathway’ is triggered by any stressor or genetic alteration that disrupts ribosomal biogenesis, and mediated by several ribosomal proteins (RPs), such as RPL11 and RPL5, which inhibit MDM2 and activate p53. Inosine monophosphate (IMP) dehydrogenase 2 (IMPDH2) is a rate-limiting enzyme in de novo guanine nucleotide biosynthesis and crucial for maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. It is highly expressed in many malignancies. We previously showed that inhibition of IMPDH2 leads to p53 activation by causing RS. Surprisingly, our current study reveals that Inauzhin (INZ), a novel non-genotoxic p53 activator by inhibiting SIRT1, can also inhibit cellular IMPDH2 activity, and reduce the levels of cellular GTP and GTP-binding nucleostemin that is essential for rRNA processing. Consequently, INZ induces RS and the RPL11/RPL5-MDM2 interaction, activating p53. These results support the new notion that INZ suppresses cancer cell growth by dually targeting SIRT1 and IMPDH2

Removal of Cu and Pb from Wastewater Using Modified Natural Zeolite

In this article, the copper and lead adsorption process using Indonesian Natural Zeolite (INZ) is studied as an adsorbent. INZ samples were obtained from Sumbermanjing Wetan, Malang district, East Java. The influence of activating acid concentration and different types of acid on the removal of copper and lead were evaluated. The activated INZ was used for adsorption of Cu and Pb from chemistry laboratory wastewater of State Islamic University of Maulana Malik Ibrahim Malang. INZ were characterized by X-ray diffraction and X-ray fluorescence spectroscopy. Characterization using XRD indicated that the activation does not affect structural changes and the diffraction pattern showed that INZ had a mordenite phase. The XRF spectra showed that increasing concentration of the activating acid simultaneously reduces undesired metal content in INZ. Determination of Cu and Pb content using Atomic Absorption Spectroscopy on wastewater showed that increasing concentration of the activating acid decreases the concentration of Cu and Pb in wastewater. The removal of Cu and Pb using INZ activated by HCl reached 61.56 % and 71 % respectively, while the removal of Cu and Pb using INZ activated by H2SO4 reached 32.86 % and 73.14 % respectively

Spectral Problems of a Class of Non-self-adjoint One-dimensional Schrodinger Operators

In this paper we investigate the one-dimensional Schrodinger operator L(q) with complex-valued periodic potential q when q\inL_{1}[0,1] and q_{n}=0 for n=0,-1,-2,..., where q_{n} are the Fourier coefficients of q with respect to the system {e^{i2{\pi}nx}}. We prove that the Bloch eigenvalues are (2{\pi}n+t)^{2} for n\inZ, t\inC and find explicit formulas for the Bloch functions. Then we consider the inverse problem for this operator

O izgradnji nove mljekare u Zagrebu

Zagrebačka mljekara i Privredna komora grada Zagreba organizirale su 13.II.1964. diskusiju o gradnji nove mljekare na osnovu teza koje su izradili inž. M. Markeš, šef sektora za plan i razvoj Zagrebačke mljekare i inz. D. Salopek, tehnolog-projektant tvornice za proizvodnju uređaja za prehrambenu industriju "Jedinstvo", Zagreb

Model Counting for Formulas of Bounded Clique-Width

We show that #SAT is polynomial-time tractable for classes of CNF formulas whose incidence graphs have bounded symmetric clique-width (or bounded clique-width, or bounded rank-width). This result strictly generalizes polynomial-time tractability results for classes of formulas with signed incidence graphs of bounded clique-width and classes of formulas with incidence graphs of bounded modular treewidth, which were the most general results of this kind known so far.Comment: Extended version of a paper published at ISAAC 201