An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

Background  

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸ or 1 × 10⁹ genomic copies of AAV1-GFP and 1 × 10⁵ transducing units of LV-dsRed.     

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.     

Precision spectroscopy and density-dependent frequency shifts in ultracold Sr

By varying the density of an ultracold 88Sr sample from 10(9) to>10(12) cm(-3), we make the first definitive measurement of the density-related frequency shift and linewidth broadening of the 1S0-3P1 optical clock transition in an alkaline earth system. In addition, we report the most accurate measurement to date of the 88Sr 1S0-3P1 optical clock transition frequency. Including a detailed analysis of systematic errors, the frequency is [434 829 121 312 334+/-20(stat)+/-33(syst)] Hz.     

A matrix‐free preconditioned Newton/GMRES method for unsteady Navier–Stokes solutions

The unsteady compressible Reynolds‐averaged Navier–Stokes equations are discretized using the Osher approximate Riemann solver with fully implicit time stepping. The resulting non‐linear system at each time step is solved iteratively using a Newton/GMRES method. In the solution process, the Jacobian matrix–vector products are replaced by directional derivatives so that the evaluation and storage of the Jacobian matrix is removed from the procedure. An effective matrix‐free preconditioner is proposed to fully avoid matrix storage. Convergence rates, computational costs and computer memory requirements of the present method are compared with those of a matrix Newton/GMRES method, a four stage Runge–Kutta explicit method, and an approximate factorization sub‐iteration method. Effects of convergence tolerances for the GMRES linear solver on the convergence and the efficiency of the Newton iteration for the non‐linear system at each time step are analysed for both matrix‐free and matrix methods. Differences in the performance of the matrix‐free method for laminar and turbulent flows are highlighted and analysed. Unsteady turbulent Navier–Stokes solutions of pitching and combined translation–pitching aerofoil oscillations are presented for unsteady shock‐induced separation problems associated with the rotor blade flows of forward flying helicopters. Copyright © 2000 John Wiley & Sons, Ltd.