A Micellar Mitotane Formulation with High Drug‐Loading and Solubility: Physico‐Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models

Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14–20 mg L^?1) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT‐loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI‐H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.     

Epistemic Horizons and the Foundations of Quantum Mechanics

In-principle restrictions on the amount of information that can be gathered about a system have been proposed as a foundational principle in several recent reconstructions of the formalism of quantum mechanics. However, it seems unclear precisely why one should be thus restricted. We investigate the notion of paradoxical self-reference as a possible origin of such epistemic horizons by means of a fixed-point theorem in Cartesian closed categories due to Lawvere that illuminates and unifies the different perspectives on self-reference.     

The shape of the nonlinearity generating the combination tone 2f1-f2

If the level behavior of the cubic difference tone is explained by a static nonlinear characteristic, the correspondence between this characteristic and certain components and quantities of the basilar membrane must be clarified. This is attempted here for a nonlinearity compatible with the idea of an active undamping feedback mechanism saturating at high levels. The relation between asymptotic behavior of the nonlinearity and the measured CDT level dependence is established. Agreement with psychoacoustic data requires a very "softly" compressing characteristic; linear or logarithmic asymptotes are ruled out. The psychoacoustically known level dependence is well reproduced for small primary-frequency differences by cancellation experiments with a digitally simulated basilar-membrane model.     

Perturbative contributions to the electroweak interface tension

The main perturbative contribution to the free energy of an electroweak interface is due to the effective potential and the tree level kinetic term. The derivative corrections are investigated with one-loop perturbation theory. The action is treated in derivative, in heat kernel, and in a multi local expansion. The massive contributions turn out to be well described by the Z-factor. The massless mode, plagued by infrared problems, is numerically less important. Its perturbatively reliable part can by calculated in derivative expansion as well. A self consistent way to include the Z-factor in the formula for the interface tension is presented.     

Fluctuations in the quark-meson model for QCD with isospin chemical potential

We study the two-flavor quark-meson (QM) model with the functional renormalization group (FRG) to describe the effects of collective mesonic fluctuations on the phase diagram of QCD at finite baryon and   isospin chemical potentials, _μB${\mu }_B$ and _μI${\mu }_I$. With only isospin chemical potential there is a precise equivalence between the competing dynamics of chiral versus pion condensation and that of collective mesonic and baryonic fluctuations in the quark-meson-diquark model for two-color QCD at finite baryon chemical potential. Here, finite _μB=3μ${\mu }_B=3\mu$ introduces an additional dimension to the phase diagram as compared to two-color QCD, however. At zero temperature, the (_μI,μ${\mu }_I,\mu$) plane of this phase diagram is strongly constrained by the “Silver Blaze problem.” In particular, the onset of pion condensation must occur at _μI=_mπ/2${\mu }_I=m_{\pi }/2$, independent of μ   as long as μ+_μI$\mu +{\mu }_I$ stays below the constituent quark mass of the QM model or the liquid-gas transition line of nuclear matter in QCD. In order to maintain this relation beyond mean field it is crucial to compute the pion mass from its timelike correlator with the FRG in a consistent way.     

Nanotextured multicrystalline Al‐BSF solar cells reaching 18% conversion efficiency using industrially viable solar cell processes

We report recent achievements in adapting industrially used solar cell processes on nanotextured surfaces. Nanostructures were etched into c‐Si surfaces by dry exothermic plasma‐less reaction of F species with Si in atmospheric pressure conditions and then modified using a short post‐etching process. Nanotextured multicrystalline wafers are used to prepare Al‐BSF solar cells using industrially feasible solar cell proc‐ essing steps. In comparison to the reference acidic textured solar cells, the nanostructured cells showed gain in short circuit current (J_sc) of up to 0.8 mA/cm² and absolute gain in conversion efficiency of up to 0.3%. The best nanotextured solar cell was independently certified to reach the conversion efficiency of 18.0%. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

On the Nodal Count for Flat Tori

We give an explicit formula for the number of nodal domains of certain eigenfunctions on a flat torus. We apply this to an isospectral but not isometric family of pairs of flat four-dimensional tori constructed by Conway and Sloane, and we show that corresponding eigenfunctions have the same number of nodal domains. This disproves a conjecture by Brüning, Gnutzmann, and Smilansky.     

Synthese,Struktur und einige Reaktionen [N-(N′,N′,N″,N″-tetramethyl)-guanidinyl]-substituierter Phosphorylverbindungen

Synthesis, Structure, and some Reactions of N-(N′,N′,N″,N″-tetramethyl)guanidinyl-substituted Phosphoryl Compounds The tetramethylguanidinyl-substituted phosphoryl compounds 1 – 10 were prepared in the reaction of the appropriate chlorophosphoryl compounds with either N′,N′,N″,N″-tetramethylguanidine (HTMG) or N-trimethylsilyl-(N′,N′,N″,N″-tetramethyl)guanidine (TMSTMG). With methyl iodide 1 reacted with N-alkylation to give the ammonium salt 11. 1 reacted with BF₃ · Et₂O at both imino nitrogen atoms with formation of the bis-BF₃-adduct 12 . The X-ray structure determination of phenylphosphonic acid-bis(N′,N′,N″,N″-tetramethylguanidinide) 3 shows shortened PN-bonds and widened PNC-angles, consistent with the partial double bond character of the PN-bond.