Photoresponsive nutlin derivatives and uses thereof

The invention relates to the field of medicine and medicinal chemistry, more in particular to the design, manufacture and use of anti-cancer drugs that can be activated by an external stimulus that can be applied in a spatiotemporal fashion. Provided herein is a compound having the chemical structure or a pharmaceutically acceptable salt thereof

Three-Body Halos. II. from Two- to Three-Body Asymptotics

The large distance behavior of weakly bound three-body systems is investigated. The Schr\"{o}dinger equation and the Faddeev equations are reformulated by an expansion in eigenfunctions of the angular part of a corresponding operator. The resulting coupled set of effective radial equations are then derived. Both two- and three-body asymptotic behavior are possible and their relative importance is studied for systems where subsystems may be bound. The system of two nucleons outside a core is studied numerically in detail and the character of possible halo structure is pointed out and investigated.Comment: 16 pages, compressed and uuencoded PosrScript file, IFA-94/3

Anisotropic magnetoresistance in a 2DEG in a quasi-random magnetic field

We present magnetotransport results for a 2D electron gas (2DEG) subject to the quasi-random magnetic field produced by randomly positioned sub-micron Co dots deposited onto the surface of a GaAs/AlGaAs heterostructure. We observe strong local and non-local anisotropic magnetoresistance for external magnetic fields in the plane of the 2DEG. Monte-Carlo calculations confirm that this is due to the changing topology of the quasi-random magnetic field in which electrons are guided predominantly along contours of zero magnetic field.Comment: 4 pages, 6 figures, submitted to Phys. Rev.

Observation of Quantum Asymmetry in an Aharonov-Bohm Ring

We have investigated the Aharonov-Bohm effect in a one-dimensional GaAs/GaAlAs ring at low magnetic fields. The oscillatory magnetoconductance of these systems are for the first time systematically studied as a function of density. We observe phase-shifts of $\pi$ in the magnetoconductance oscillations, and halving of the fundamental $h/e$ period, as the density is varied. Theoretically we find agreement with the experiment, by introducing an asymmetry between the two arms of the ring.Comment: 4 pages RevTex including 3 figures, submitted to Phys. Rev.

Effect of intersubband scattering on weak localization in 2D systems

The theory of weak localization is generalized for multilevel 2D systems taking into account intersubband scattering. It is shown that weak intersubband scattering which is negligible in a classical transport, affects strongly the weak-localization correction to conductivity. The anomalous magnetoresistance is calculated in the whole range of classically low magnetic fields. This correction to conductivity is shown to depend strongly on the ratios of occupied level concentrations. It is demonstrated that at relatively low population of the excited subband, it is necessary to use the present theory because the high-field limit asimptotics is shown to be achieved only in classical magnetic fields.Comment: 18 pages, 4 figures. Accepted to Phys. Rev. B 6

The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan

Background: Endothelin A receptor antagonists (ETARA) slow chronic kidney disease (CKD) progression but their use is limited due to fluid retention and associated clinical risks. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) cause osmotic diuresis and improve clinical outcomes in CKD and heart failure. We hypothesized that co-administration of the SGLT2i dapagliflozin with the ETARA zibotentan would mitigate the fluid retention risk using hematocrit (Hct) and bodyweight as proxies for fluid retention.Methods: Experiments were performed in 4% salt fed WKY rats. First, we determined the effect of zibotentan (30, 100 or 300 mg/kg/day) on Hct and bodyweight. Second, we assessed the effect of zibotentan (30 or 100 mg/kg/day) alone or in combination with dapagliflozin (3 mg/kg/day) on Hct and bodyweight.Results: Hct at Day 7 was lower in zibotentan versus vehicle groups [zibotentan 30 mg/kg/day, 43% (standard error 1); 100 mg/kg/day, 42% (1); and 300 mg/kg/day, 42% (1); vs vehicle, 46% (1); P &lt;. 05], while bodyweight was numerically higher in all zibotentan groups compared with vehicle. Combining zibotentan with dapagliflozin for 7 days prevented the change in Hct [zibotentan 100 mg/kg/day and dapagliflozin, 45% (1); vs vehicle 46% (1); P =. 44] and prevented the zibotentan-driven increase in bodyweight (zibotentan 100 mg/kg/day + dapagliflozin 3 mg/kg/day = -3.65 g baseline corrected bodyweight change; P =. 15).Conclusions: Combining ETARA with SGLT2i prevents ETARA-induced fluid retention, supporting clinical studies to assess the efficacy and safety of combining zibotentan and dapagliflozin in individuals with CKD.</p

The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan

Background: Endothelin A receptor antagonists (ETARA) slow chronic kidney disease (CKD) progression but their use is limited due to fluid retention and associated clinical risks. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) cause osmotic diuresis and improve clinical outcomes in CKD and heart failure. We hypothesized that co-administration of the SGLT2i dapagliflozin with the ETARA zibotentan would mitigate the fluid retention risk using hematocrit (Hct) and bodyweight as proxies for fluid retention.Methods: Experiments were performed in 4% salt fed WKY rats. First, we determined the effect of zibotentan (30, 100 or 300 mg/kg/day) on Hct and bodyweight. Second, we assessed the effect of zibotentan (30 or 100 mg/kg/day) alone or in combination with dapagliflozin (3 mg/kg/day) on Hct and bodyweight.Results: Hct at Day 7 was lower in zibotentan versus vehicle groups [zibotentan 30 mg/kg/day, 43% (standard error 1); 100 mg/kg/day, 42% (1); and 300 mg/kg/day, 42% (1); vs vehicle, 46% (1); P &lt;. 05], while bodyweight was numerically higher in all zibotentan groups compared with vehicle. Combining zibotentan with dapagliflozin for 7 days prevented the change in Hct [zibotentan 100 mg/kg/day and dapagliflozin, 45% (1); vs vehicle 46% (1); P =. 44] and prevented the zibotentan-driven increase in bodyweight (zibotentan 100 mg/kg/day + dapagliflozin 3 mg/kg/day = -3.65 g baseline corrected bodyweight change; P =. 15).Conclusions: Combining ETARA with SGLT2i prevents ETARA-induced fluid retention, supporting clinical studies to assess the efficacy and safety of combining zibotentan and dapagliflozin in individuals with CKD.</p