Decreased soluble guanylate cyclase contributes to cardiac dysfunction induced by chronic doxorubicin treatment in mice

Aims: The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity. Results: Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC alpha 1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC alpha 1 allele [sGC alpha 1(-/-CM)]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGC alpha 1(-/-CM) than WT mice. To further assess whether reduced sGC activity plays a pathogenic role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which decreased cardiac sGC activity was induced by cardiomyocyte-specific expression of a dominant negative sGC alpha 1 mutant (DNsGC alpha 1) upon doxycycline removal (Tet-off). After 8 weeks of doxorubicin administration, DNsGC alpha 1(tg/+), but not WT, mice displayed LV systolic dysfunction and dilatation. The difference in cardiac function and remodeling between DNsGC alpha 1(tg/+) and WT mice was even more pronounced after 12 weeks of treatment. Further impairment of cardiac function was attenuated when DNsGC alpha 1 gene expression was inhibited (beginning at 8 weeks of doxorubicin treatment) by administering doxycycline. Furthermore, doxorubicin-associated reactive oxygen species generation was higher in sGC alpha 1-deficient than WT hearts. Innovation and Conclusion: These data demonstrate that a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in mice and identify sGC as a potential therapeutic target. Various pharmacological sGC agonists are in clinical development or use and may represent a promising approach to limit doxorubicin-associated cardiotoxicity

Light-cone-like spreading of correlations in a quantum many-body system

How fast can correlations spread in a quantum many-body system? Based on the seminal work by Lieb and Robinson, it has recently been shown that several interacting many-body systems exhibit an effective light cone that bounds the propagation speed of correlations. The existence of such a "speed of light" has profound implications for condensed matter physics and quantum information, but has never been observed experimentally. Here we report on the time-resolved detection of propagating correlations in an interacting quantum many-body system. By quenching a one-dimensional quantum gas in an optical lattice, we reveal how quasiparticle pairs transport correlations with a finite velocity across the system, resulting in an effective light cone for the quantum dynamics. Our results open important perspectives for understanding relaxation of closed quantum systems far from equilibrium as well as for engineering efficient quantum channels necessary for fast quantum computations.Comment: 7 pages, 5 figures, 2 table

Observation of mesoscopic crystalline structures in a two-dimensional Rydberg gas

The ability to control and tune interactions in ultracold atomic gases has paved the way towards the realization of new phases of matter. Whereas experiments have so far achieved a high degree of control over short-ranged interactions, the realization of long-range interactions would open up a whole new realm of many-body physics and has become a central focus of research. Rydberg atoms are very well-suited to achieve this goal, as the van der Waals forces between them are many orders of magnitude larger than for ground state atoms. Consequently, the mere laser excitation of ultracold gases can cause strongly correlated many-body states to emerge directly when atoms are transferred to Rydberg states. A key example are quantum crystals, composed of coherent superpositions of different spatially ordered configurations of collective excitations. Here we report on the direct measurement of strong correlations in a laser excited two-dimensional atomic Mott insulator using high-resolution, in-situ Rydberg atom imaging. The observations reveal the emergence of spatially ordered excitation patterns in the high-density components of the prepared many-body state. They have random orientation, but well defined geometry, forming mesoscopic crystals of collective excitations delocalised throughout the gas. Our experiment demonstrates the potential of Rydberg gases to realise exotic phases of matter, thereby laying the basis for quantum simulations of long-range interacting quantum magnets.Comment: 10 pages, 7 figure

Practising Mathematics Teacher Education: Expanding The Realm of Possibilities

It is often said that student teachers’ underlying beliefs of what mathematics consists of and how it should be taught are restricted in two ways. On the one hand, future elementary teachers in general use only weak mathematical conceptions, which often do not help them to realise their educational ambitions. On a general educational level, many of these students advocate discovery learning and collective problem solving, but when it comes down to the mathematical activities that have to be prepared, their experience of “traditional” school mathematics is of little help. On the other hand, future (higher) secondary teachers mostly are very well prepared with respect to formal academic mathematics when entering mathematics education programmes, either because they have already passed a mathematical formation at university or because their teacher education programmes emphasise the study of academic mathematics and not of educational or didactical modules

A Rydberg Quantum Simulator

Following Feynman and as elaborated on by Lloyd, a universal quantum simulator (QS) is a controlled quantum device which reproduces the dynamics of any other many particle quantum system with short range interactions. This dynamics can refer to both coherent Hamiltonian and dissipative open system evolution. We investigate how laser excited Rydberg atoms in large spacing optical or magnetic lattices can provide an efficient implementation of a universal QS for spin models involving (high order) n-body interactions. This includes the simulation of Hamiltonians of exotic spin models involving n-particle constraints such as the Kitaev toric code, color code, and lattice gauge theories with spin liquid phases. In addition, it provides the ingredients for dissipative preparation of entangled states based on engineering n-particle reservoir couplings. The key basic building blocks of our architecture are efficient and high-fidelity n-qubit entangling gates via auxiliary Rydberg atoms, including a possible dissipative time step via optical pumping. This allows to mimic the time evolution of the system by a sequence of fast, parallel and high-fidelity n-particle coherent and dissipative Rydberg gates.Comment: 8 pages, 4 figure

Designing spin-1 lattice models using polar molecules

We describe how to design a large class of always on spin-1 interactions between polar molecules trapped in an optical lattice. The spin degrees of freedom correspond to the hyperfine levels of a ro-vibrational ground state molecule. Interactions are induced using a microwave field to mix ground states in one hyperfine manifold with the spin entangled dipole-dipole coupled excited states. Using multiple fields anistropic models in one, two, or three dimensions, can be built with tunable spatial range. An illustrative example in one dimension is the generalized Haldane model, which at a specific parameter has a gapped valence bond solid ground state. The interaction strengths are large compared to decoherence rates and should allow for probing the rich phase structure of strongly correlated systems, including dimerized and gapped phases.Comment: 24 pages, 5 figure

Quantum quenches in the anisotropic spin-1/2 Heisenberg chain: different approaches to many-body dynamics far from equilibrium

Recent experimental achievements in controlling ultracold gases in optical lattices open a new perspective on quantum many-body physics. In these experimental setups it is possible to study coherent time evolution of isolated quantum systems. These dynamics reveal new physics beyond the low-energy properties usually relevant in solid-state many-body systems. In this paper we study the time evolution of antiferromagnetic order in the Heisenberg chain after a sudden change of the anisotropy parameter, using various numerical and analytical methods. As a generic result we find that the order parameter, which can show oscillatory or non-oscillatory dynamics, decays exponentially except for the effectively non-interacting case of the XX limit. For weakly ordered initial states we also find evidence for an algebraic correction to the exponential law. The study is based on numerical simulations using a numerical matrix product method for infinite system sizes (iMPS), for which we provide a detailed description and an error analysis. Additionally, we investigate in detail the exactly solvable XX limit. These results are compared to approximative analytical approaches including an effective description by the XZ-model as well as by mean-field, Luttinger-liquid and sine-Gordon theories. This reveals which aspects of non-equilibrium dynamics can as in equilibrium be described by low-energy theories and which are the novel phenomena specific to quantum quench dynamics. The relevance of the energetically high part of the spectrum is illustrated by means of a full numerical diagonalization of the Hamiltonian.Comment: 28 page

A state-dependent quantification of climate sensitivity based in paleo data of the last 2.1 million years

The evidence from both data and models indicates that specific equilibrium climate sensitivity S[X] — the global annual mean surface temperature change (DTg) as a response to a change in radiative forcing X (DR[X]) — is state-dependent. Such a state dependency implies that the best fit in the scatter plot of (DTg versus DR[X] is not a linear regression, but can be some non-linear or even non-smooth function. While for the conventional linear case the slope (gradient) of the regression is correctly interpreted as the specific equilibrium climate sensitivity S[X], the interpretation is not straightforward in the non-linear case. We here explain how such a state-dependent scatter plot needs to be interpreted, and provide a theoretical understanding — or generalization — how to quantify S[X] in the non-linear case. Finally, from data covering the last 2.1 Myr we show that — due to state dependency — the specific equilibrium climate sensitivity which considers radiative forcing of CO2 and land ice sheet (LI) albedo, S[CO2;LI], is larger during interglacial states than during glacial conditions by more than a factor two

Trapped Rydberg Ions: From Spin Chains to Fast Quantum Gates

We study the dynamics of Rydberg ions trapped in a linear Paul trap, and discuss the properties of ionic Rydberg states in the presence of the static and time-dependent electric fields constituting the trap. The interactions in a system of many ions are investigated and coupled equations of the internal electronic states and the external oscillator modes of a linear ion chain are derived. We show that strong dipole-dipole interactions among the ions can be achieved by microwave dressing fields. Using low-angular momentum states with large quantum defect the internal dynamics can be mapped onto an effective spin model of a pair of dressed Rydberg states that describes the dynamics of Rydberg excitations in the ion crystal. We demonstrate that excitation transfer through the ion chain can be achieved on a nanosecond timescale and discuss the implementation of a fast two-qubit gate in the ion chain.Comment: 26 pages, 9 figure

Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1

Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analyzed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV)