Controlling the biological effects of spermine using a synthetic receptor

Polyamines play an important role in biology, yet their exact function in many processes is poorly understood. Artificial host molecules capable of sequestering polyamines could be useful tools for studying their cellular function. However, designing synthetic receptors with affinities sufficient to compete with biological polyamine receptors remains a huge challenge. Binding affinities of synthetic hosts are typically separated by a gap of several orders of magnitude from those of biomolecules. We now report that a dynamic combinatorial selection approach can deliver a synthetic receptor that bridges this gap. The selected receptor binds spermine with a dissociation constant of 22 nM, sufficient to remove it from its natural host DNA and reverse some of the biological effects of spermine on the nucleic acid. In low concentrations, spermine induces the formation of left-handed DNA, but upon addition of our receptor, the DNA reverts back to its right-handed form. NMR studies and computer simulations suggest that the spermine complex has the form of a pseudo-rotaxane. The spermine receptor is a promising lead for the development of therapeutics or molecular probes for elucidating spermine's role in cell biology.     

Backlund transformations and exact solutions for a nonlinear elliptic equation modelling isothermal magnetostatic atmosphere

The equations of magnetostatic equilibria for a plasma in agravitational field are investigated analytically. For equilibriawith an ignorable spatial coordinate, the equations reduce toa single nonlinear elliptic equation for the magnetic potentialu known as the Grad-Shafranov equation. By specifying the arbitraryfunctions in this equation, a Liouville equation is obtained.Bäcklund transformations are described and applied to obtainexact solutions for the Liouville equation modelling an isothermalmagnetostatic atmosphere, in which the current density J isproportional to the exponential of the magnetic potential andmoveover falls off exponentially with distance vertical to thebase with an e-folding distance equal to the gravitational scaleheight.     

Working group report: Heavy-ion physics and quark-gluon plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of quark-gluon plasma believed to have created in heavy-ion collisions and in early Universe are reported.     

Optical clock and ultracold collisions with trapped strontium atoms

With microkelvin neutral strontium atoms confined in an optical lattice, we have achieved a fractional resolution of better than 5×10^–15 on the ¹ S ₀–³ P ₀ doubly forbidden ⁸⁷Sr clock transition at 698 nm. Measurements of the clock line shifts as a function of experimental parameters indicate that the fractional uncertainties due to systematic shifts could be reduced below 10^–15. The ultrahigh spectral resolution permitted resolving the nuclear spin states of the clock transition at small magnetic fields, leading to measurements of the ³ P ₀ magnetic moment and metastable lifetime. In addition, photoassociation spectroscopy was performed on the narrow ¹ S ₀–³ P ₁ transition of ⁸⁸Sr, revealing the least-bound state, and showing promise for efficient optical tuning of the ground state scattering length and production of cold molecules.     

C–H functionalisation tolerant to polar groups could transform fragment-based drug discovery (FBDD)

We have analysed 131 fragment-to-lead (F2L) examples targeting a wide variety of protein families published by academic and industrial laboratories between 2015–2019. Our assessment of X-ray structural data identifies the most common polar functional groups involved in fragment-protein binding are: N–H (hydrogen bond donors on aromatic and aliphatic N–H, amides and anilines; totalling 35%), aromatic nitrogen atoms (hydrogen bond acceptors; totalling 23%), and carbonyl oxygen group atoms (hydrogen bond acceptors on amides, ureas and ketones; totalling 22%). Furthermore, the elaboration of each fragment into its corresponding lead is analysed to identify the nominal synthetic growth vectors. In ∼80% of cases, growth originates from an aromatic or aliphatic carbon on the fragment and more than 50% of the total bonds formed are carbon–carbon bonds. This analysis reveals that growth from carbocentric vectors is key and therefore robust C–H functionalisation methods that tolerate the innate polar functionality on fragments could transform fragment-based drug discovery (FBDD). As a further resource to the community, we have provided the full data of our analysis as well as an online overlay page of the X-ray structures of the fragment hit and leads: https://astx.com/interactive/F2L-2021/

An in depth meta analysis of 131 fragment-to-lead case-studies has shown the importance of synthetic methods that allow carbon-centred synthetic elaboration in the presence of polar pharmacophores.     

Cancellation of stark shifts in optical lattice clocks by use of pulsed Raman and electromagnetically induced transparency techniques

We propose a combination of electromagnetically induced transparency-Raman and pulsed spectroscopy techniques to accurately cancel frequency shifts arising from electromagnetically induced transparency fields in forbidden optical clock transitions of alkaline earth atoms. At appropriate detunings, time-separated laser pulses are designed to trap atoms in coherent superpositions while eliminating off-resonance ac Stark contributions, achieving efficient population transfer up to 60% with inaccuracy <10(-17). Results from the wave-function formalism are confirmed by the density matrix approach.     

Synthetic and biological membranes: Common phenomena

Many of the processes occurring in nature involve membrane transport. Some of the functions performed by such membranes appear to be unique, as well as efficient, and it would be possible to make synthetic membranes having similar properties. This paper discusses some of these phenomena. Further, it may be quite possible that knowledge of synthetic membranes can be extended to better understand the changes which occur in biological ones, and this is also mentioned here.     

Narrow line cooling: finite photon recoil dynamics

We present an extensive study of the unique thermal and mechanical dynamics for narrow-line cooling on the 1S0-3P1 88Sr transition. For negative detuning, trap dynamics reveal a transition from the semiclassical regime to the photon-recoil-dominated quantum regime, yielding an absolute minima in the equilibrium temperature below the single-photon-recoil limit. For positive detuning, the cloud divides into discrete momentum packets whose alignment mimics lattice points on a face-centered-cubic crystal. This novel behavior arises from velocity selection and "positive feedback" acceleration due to a finite number of photon recoils. Cooling is also achieved with blue-detuned light around a velocity where gravity balances the radiative force.     

Coherent optical phase transfer over a 32-km fiber with 1 s instability at 10{-17}

The phase coherence of an ultrastable optical frequency reference is fully maintained over actively stabilized fiber networks of lengths exceeding 30 km. For a 7-km link installed in an urban environment, the transfer instability is 6 x 10{-18} at 1 s. The excess phase noise of 0.15 rad, integrated from 8 mHz to 25 MHz, yields a total timing jitter of 0.085 fs. A 32-km link achieves similar performance. Using frequency combs at each end of the coherent-transfer fiber link, a heterodyne beat between two independent ultrastable lasers, separated by 3.5 km and 163 THz, achieves a 1-Hz linewidth.