All-magnonic repeater based on bistability.

Bistability, a universal phenomenon found in diverse fields such as biology, chemistry, and physics, describes a scenario in which a system has two stable equilibrium states and resets to one of the two states. The ability to switch between these two states is the basis for a wide range of applications, particularly in memory and logic operations. Here, we present a universal approach to achieve bistable switching in magnonics, the field processing data using spin waves.

Health Data Re-Identification: Assessing Adversaries and Potential Harms.

Sharing biomedical data for research can help to improve disease understanding and support the development of preventive, diagnostic, and therapeutic methods. However, it is vital to balance the amount of data shared and the sharing mechanism chosen with the privacy protection provided. This requires a detailed understanding of potential adversaries who might attempt to re-identify data and the consequences of their actions.

Stimulated Amplification of Propagating Spin Waves.

Spin-wave amplification techniques are key to the realization of magnon-based computing concepts. We introduce a novel mechanism to amplify spin waves in magnonic nanostructures. Using the technique of rapid cooling, we create a nonequilibrium state in excess of high-energy magnons and demonstrate the stimulated amplification of an externally seeded, propagating spin wave.

The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2.

A metabotropic glutamate receptor coupled to phospholipase D (PLD-mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypical glutamate receptor. A receptor with the same pharmacology is present in spindle primary sensory terminals where its blockade can totally abolish, and its activation can double, the normal stretch-evoked firing.

Deeply nonlinear excitation of self-normalized short spin waves.

Spin waves are ideal candidates for wave-based computing, but the construction of magnetic circuits is blocked by a lack of an efficient mechanism to excite long-running exchange spin waves with normalized amplitudes. Here, we solve the challenge by exploiting a deeply nonlinear phenomenon for forward volume spin waves in 200-nm-wide nanoscale waveguides and validate our concept using microfocused Brillouin light scattering spectroscopy. An unprecedented nonlinear frequency shift of more than 2 GHz is achieved, corresponding to a magnetization precession angle of 55° and enabling the excitation of spin waves with wavelengths down to 200 nm.

Routine post-pull chest radiograph is not necessary after VATS lobectomy.

Introduction: There is no consensus on postoperative thoracostomy tube management in thoracic patients, specifically whether or not a chest radiograph is required after tube removal.

Methods: Retrospective review of video-assisted thoracoscopic (VATS) lobectomy patients was performed at a large tertiary referral center from January 1, 2019 to December 31, 2020. Patients were grouped as asymptomatic or symptomatic after thoracostomy removal.

Characterization of transit rates in the large intestine of mice following treatment with a CGRP antibody, CGRP receptor antibody, and small molecule CGRP receptor antagonists.

Objective: To characterize the effects of blocking calcitonin gene-related peptide (CGRP) activity in a mouse model of gastrointestinal transport.

Background: Migraine management using CGRP modulating therapies can cause constipation of varying frequency and severity. This variation might be due to the different mechanisms through which therapies block CGRP activity (e.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody.

Control of the Bose-Einstein Condensation of Magnons by the Spin Hall Effect.

Previously, it has been shown that rapid cooling of yttrium-iron-garnet-platinum nanostructures, preheated by an electric current sent through the Pt layer, leads to overpopulation of a magnon gas and to subsequent formation of a Bose-Einstein condensate (BEC) of magnons. The spin Hall effect (SHE), which creates a spin-polarized current in the Pt layer, can inject or annihilate magnons depending on the electric current and applied field orientations. Here we demonstrate that the injection or annihilation of magnons via the SHE can prevent or promote the formation of a rapid cooling-induced magnon BEC.

Regioselective Magnesiation and Zincation Reactions of Aromatics and Heterocycles Triggered by Lewis Acids.

Mixed TMP-bases (TMP=2,2,6,6-tetramethylpiperidyl), such as TMPMgCl ⋅ LiCl, TMP Mg ⋅ 2LiCl, TMPZnCl ⋅ LiCl and TMP Zn ⋅ 2LiCl, are outstanding reagents for the metalation of functionalized aromatics and heterocycles. In the presence of Lewis acids, such as BF  ⋅ OEt or MgCl , the metalation scope of such bases was dramatically increased, and regioselectivity switches were achieved in the presence or absence of these Lewis acids. Furthermore, highly reactive lithium bases, such as TMPLi or Cy NLi, are also compatible with various Lewis acids, such as MgCl  ⋅ 2LiCl, ZnCl  ⋅ 2LiCl or CuCN ⋅ 2LiCl.

Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in Toluene.

The continuous flow reaction of various aryl or heteroaryl bromides in toluene in the presence of THF (1.0 equiv) with sec-BuLi (1.1 equiv) provided at 25 °C within 40 sec the corresponding aryllithiums which were acylated with various functionalized N,N-dimethylamides including easily enolizable amides at -20 °C within 27 sec, producing highly functionalized ketones in 48-90 % yield (36 examples).

Regioselective difunctionalization of pyridines 3,4-pyridynes.

A new regioselective 3,4-difunctionalization of 3-chloropyridines 3,4-pyridyne intermediates is reported. Regioselective lithiation of 3-chloro-2-ethoxypyridine and a related 2-thio-derivative followed by treatment with aryl- and alkylmagnesium halides as well as magnesium thiolates at -78 °C produced 3,4-pyridynes during heating to 75 °C. Regioselective addition of the Grignard moiety in position 4 followed by an electrophilic quench in position 3 led to various 2,3,4-trisubstituted pyridines.

LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants.

Unlabelled: SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab).

The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19).

Controlling the Nonlinear Relaxation of Quantized Propagating Magnons in Nanodevices.

Relaxation of linear magnetization dynamics is well described by the viscous Gilbert damping processes. However, for strong excitations, nonlinear damping processes such as the decay via magnon-magnon interactions emerge and trigger additional relaxation channels. Here, we use space- and time-resolved microfocused Brillouin light scattering spectroscopy and micromagnetic simulations to investigate the nonlinear relaxation of strongly driven propagating spin waves in yttrium iron garnet nanoconduits.

LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection.

Unlabelled: SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity.

Propagation of Spin-Wave Packets in Individual Nanosized Yttrium Iron Garnet Magnonic Conduits.

Modern-day CMOS-based computation technology is reaching its fundamental limitations. The emerging field of magnonics, which utilizes spin waves for data transport and processing, proposes a promising path to overcome these limitations. Different devices have been demonstrated recently on the macro- and microscale, but the feasibility of the magnonics approach essentially relies on the scalability of the structure feature size down to the extent of a few 10 nm, which are typical sizes for the established CMOS technology.

Bose-Einstein condensation of quasiparticles by rapid cooling.

The fundamental phenomenon of Bose-Einstein condensation has been observed in different systems of real particles and quasiparticles. The condensation of real particles is achieved through a major reduction in temperature, while for quasiparticles, a mechanism of external injection of bosons by irradiation is required. Here, we present a new and universal approach to enable Bose-Einstein condensation of quasiparticles and to corroborate it experimentally by using magnons as the Bose-particle model system.

Selective Acylation of Aryl- and Heteroarylmagnesium Reagents with Esters in Continuous Flow.

A selective acylation of readily accessible organomagnesium reagents with commercially available esters proceeds at convenient temperatures and short residence times in continuous flow. Flow conditions allow us to prevent premature collapse of the hemiacetal intermediates despite noncryogenic conditions, thus furnishing ketones in good yields. Throughout, the coordinating ability of the ester and/or Grignard was crucial for the reaction outcome.

Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1,3)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor.

Clinical development of catechol-based orthosteric agonists of the dopamine D1 receptor has thus far been unsuccessful due to multiple challenges. To address these issues, we identified LY3154207 () as a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity. Conformational studies showed LY3154207 adopts an unusual boat conformation, and a binding pose with the human D1 receptor was proposed based on this observation.

Spin Pinning and Spin-Wave Dispersion in Nanoscopic Ferromagnetic Waveguides.

Spin waves are investigated in yttrium iron garnet waveguides with a thickness of 39 nm and widths ranging down to 50 nm, i.e., with an aspect ratio thickness over width approaching unity, using Brillouin light scattering spectroscopy.

Amination of Phosphorodiamidate-Substituted Pyridines and Related N-Heterocycles with Magnesium Amides.

The amination of various phosphorodiamidate-substituted pyridines, quinolines, and quinoxaline with magnesium amides RNMgCl·LiCl proceeds at room temperature within 8 h. Several pharmaceutically active amines were suitable substrates for this amination procedure, and also the antihistaminic tripelennamine was prepared. Additionally, several heterocyclic phosphorodiamidates underwent directed ortho-metalation (D oM) using TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) or TMPMg·2LiCl, followed by electrophilic functionalization prior to the amination step, which led to ortho-functionalized aminated N-heterocycles.

Intracellular Binding Site for a Positive Allosteric Modulator of the Dopamine D1 Receptor.

The binding site for DETQ [2-(2,6-dichlorophenyl)-1-((1,3)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1)-yl)ethan-1-one], a positive allosteric modulator (PAM) of the dopamine D1 receptor, was identified and compared with the binding site for CID 2886111 [-(6--butyl-3-carbamoyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)pyridine-4-carboxamide], a reference D1 PAM. From D1/D5 chimeras, the site responsible for potentiation by DETQ of the increase in cAMP in response to dopamine was narrowed down to the N-terminal intracellular quadrant of the receptor; arginine-130 in intracellular loop 2 (IC2) was then identified as a critical amino acid based on a human/rat species difference. Confirming the importance of IC2, a 2-adrenergic receptor construct in which the IC2 region was replaced with its D1 counterpart gained the ability to respond to DETQ.

Mutations in the fourth β-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers.

Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.

Synthesis and Pharmacological Characterization of C4-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1 S,2 S,4 S,5 R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu Receptor Agonist.

Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu) receptors, but small molecule tools are lacking. As part of our ongoing efforts to identify potent, selective, and systemically bioavailable agonists for mGlu and mGlu receptor subtypes, a series of C4-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino-bicyclo[3.1.