Total positive curvature of circular DNA

The interplay between global constraints and local material properties of chain molecules is a subject of emerging interest. Studies of molecules that are intrinsically chiral, such as double-stranded DNA, is one example. Their properties generally depend on the local geometry, i.e. on curvature and torsion, yet the paths of closed molecules are globally restricted by topology. Molecules that fulfill a twist neutrality condition, a zero sum rule for the incremental change in the rate of winding along the curve, will behave neutrally to strain. This has implications for plasmids. For small circular microDNAs it follows that there must exist a minimum length for these to be double-stranded. It also follows that all microDNAs longer than the minimum length must be concave. This counterintuitive result is consistent with the kink-like appearance which has been observed for circular DNA. A prediction for the total negative curvature of a circular microDNA is given as a function of its length.Comment: 6 pages, 1 figure; v2: references added;v3: a crucial mistake in Eq. (8) of v2 has been corrected, and the conclusions changed accordingl

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment.

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients' response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes

Investigation of the Dzyaloshinskii-Moriya interaction and room temperature skyrmions in W/CoFeB/MgO thin films and microwires

Recent studies have shown that material structures, which lack structural inversion symmetry and have high spin-orbit coupling can exhibit chiral magnetic textures and skyrmions which could be a key component for next generation storage devices. The Dzyaloshinskii-Moriya Interaction (DMI) that stabilizes skyrmions is an anti-symmetric exchange interaction favoring non-collinear orientation of neighboring spins. It has been shown that material systems with high DMI can lead to very efficient domain wall and skyrmion motion by spin-orbit torques. To engineer such devices, it is important to quantify the DMI for a given material system. Here we extract the DMI at the Heavy Metal (HM) /Ferromagnet (FM) interface using two complementary measurement schemes namely asymmetric domain wall motion and the magnetic stripe annihilation. By using the two different measurement schemes, we find for W(5 nm)/Co20Fe60B20(0.6 nm)/MgO(2 nm) the DMI to be 0.68 +/- 0.05 mJ/m2 and 0.73 +/- 0.5 mJ/m2, respectively. Furthermore, we show that this DMI stabilizes skyrmions at room temperature and that there is a strong dependence of the DMI on the relative composition of the CoFeB alloy. Finally we optimize the layers and the interfaces using different growth conditions and demonstrate that a higher deposition rate leads to a more uniform film with reduced pinning and skyrmions that can be manipulated by Spin-Orbit Torques

Thymic epithelial organoids mediate T-cell development

Although the advent of organoids has opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here, we established organoids from the thymus, the lymphoid organ responsible for T-cell development. We identified conditions enabling mouse thymic epithelial progenitor cell proliferation and development into organoids with diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. In contrast to these two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T-cell development upon reaggregation with T-cell progenitors. The reaggregates showed in vivo-like epithelial diversity and the ability to attract T-cell progenitors. Thymic epithelial organoids are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T-cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries