Rybergharding9636

We report herein a cobalt-catalyzed 8-aminoquinoline-directed highly regio- and stereoselective C-H/N-H activation annulation of indole-2-carboxamides with 1,2-dihydronaphthalene for the synthesis of β-carboline-1-one derivatives at room temperature. A cheaper and commercially available cobalt catalyst has been used for this transformation. The protocol tolerates a wide range of functionalities, affording β-carboline-1-one derivatives in good yields. An initial mechanistic study revealed a reversible cyclometalation to be operative.Computational chemistry applications have become an integral part of the drug discovery workflow over the past 35 years. However, computational modeling in support of drug development has remained a relatively uncharted territory for a significant part of both academic and industrial communities. This review considers the computational modeling workflows for three key components of drug preclinical and clinical development, namely, process chemistry, analytical research and development, as well as drug product and formulation development. An overview of the computational support for each step of the respective workflows is presented. Additionally, in context of solid form design, special consideration is given to modern physics-based virtual screening methods. This covers rational approaches to polymorph, coformer, counterion, and solvent virtual screening in support of solid form selection and design.The skins of chameleons have attracted growing interest because they have sensitive mechano-chromic properties and bright colors due to the large surface-to-surface distances (Ds-s) between neighboring particles and contrast of the refractive index (Δn), respectively. Inspired by these, artificial mechano-chromic photonic skins (MPSs) mimicking those of chameleons were fabricated by the large Δn and Ds-s. The fabrication is considerably simple and efficient based on the self-assembly strategy using commercial chemicals and materials. The reflectance of MPSs depends on the value of Δn, which can be greatly increased to 70% with a Δn of 0.035, leading to their brilliant colors. Because of the large Ds-s, the MPSs possess outstanding mechano-chromic performances, including a large maximal (Δλ = 205 nm) and effective (Δλe = 184 nm) tuning range of the reflection wavelength, high sensitivity (368), fast responsiveness (2.2 nm/ms), good stabilities (>1 year), and reversibility (>100 times). Based on these advantages, MPSs have been used for self-reporting the strain of earthworms by outputting diverse colors during the peristaltic process, indicating the great potential of the MPSs as visual sensors and optical coatings.Computational chemistry is an increasingly active field due to the improvement of computing resources and theoretical tools. However, its use remains usually limited to technically inclined users due to the technical challenges of preparing, launching, and analyzing calculations. In this context, we have developed CalcUS, an open-source platform to streamline quantum chemistry studies. Its objective is to democratize access to computational chemistry by providing a user-friendly web interface to simplify running and analyzing quantum mechanical calculations. It is freely available, expandable, and customizable. It promotes connectivity to multiple software packages and algorithms, thus providing state-of-the-art techniques to all practitioners. We propose CalcUS as a standalone tool and infrastructure to support other open-source packages.A crystallographically heterogeneous interface was fabricated by growing hexagonal graphene (Gr) using chemical vapor deposition (CVD) on a tetragonal FePd epitaxial film grown by magnetron sputtering. FePd was alternately arranged with Fe and Pd in the vertical direction, and the outermost surface atom was identified primarily as Fe rather than Pd. This means that FePd has a high degree of L10-ordering, and the outermost Fe bonds to the carbon of Gr at the interface. When Gr is grown by CVD, the crystal orientation of hexagonal Gr toward tetragonal L10-FePd selects an energetically stable structure based on the van der Waals (vdW) force. The atomic relationship of Gr/L10-FePd, which is an energetically stable interface, was unveiled theoretically and experimentally. The Gr armchair axis was parallel to FePd [100]L10, where Gr was under a small strain by chemical bonding. Focusing on the interatomic distance between the Gr and FePd layers, the distance was theoretically and experimentally determined to be appe. From a practical viewpoint, IPMA is useful because it can be incorporated into the large bulk perpendicular magnetic anisotropy (PMA) of L10-FePd. A micromagnetic simulation assuming both PMA and IPMA predicted that perpendicularly magnetized magnetic tunnel junctions (p-MTJs) using Gr/L10-FePd could realize 10-year data retention in a small recording layer with a circular diameter and thickness of 10 and 2 nm, respectively. We unveiled the energetically stable atomic structure in the crystallographically heterogeneous interface, discovered the emergence of the robust IPMA, and predicted that the Gr/L10-FePd p-MTJ is significant for high-density X nm generation magnetic random-access memory (MRAM) applications.Natural killer (NK) cells, in addition to their cytotoxicity function, harbor prominent cytokine production capabilities and contribute to regulating autoimmune responses. T-cell immunoglobulin and mucin domain containing protein-3 (Tim-3) is one of the inhibitory receptors on NK cells and a promising immune checkpoint target. We recently found that phosphatidylserine (PS) binding to Tim-3 can suppress NK cell activation. Therefore, based on the therapeutic potential of Tim-3 in NK-cell-mediated diseases, we developed a photoswitchable ligand of Tim-3, termed photophosphatidylserine (phoPS), that mimics the effects of PS. Upon 365 or 455 nm light irradiation, the isomer of phoPS cyclically conversed the cis/trans configuration, resulting in an active/inactive Tim-3 ligand, thus modulating the function of NK cells in vitro and in vivo. We also demonstrated that reversible phoPS enabled optical control of acute hepatitis. Together, phoPS may be an appealing tool for autoimmune diseases and cytokine storms in the future.The ability to create nanometer-scale lateral p-n junctions is essential for the next generation of two-dimensional (2D) devices. Using the charge-transfer heterostructure graphene/α-RuCl3, we realize nanoscale lateral p-n junctions in the vicinity of graphene nanobubbles. Our multipronged experimental approach incorporates scanning tunneling microscopy (STM) and spectroscopy (STS) and scattering-type scanning near-field optical microscopy (s-SNOM) to simultaneously probe the electronic and optical responses of nanobubble p-n junctions. Our STM/STS results reveal that p-n junctions with a band offset of ∼0.6 eV can be achieved with widths of ∼3 nm, giving rise to electric fields of order 108 V/m. Concurrent s-SNOM measurements validate a point-scatterer formalism for modeling the interaction of surface plasmon polaritons (SPPs) with nanobubbles. Ab initio density functional theory (DFT) calculations corroborate our experimental data and reveal the dependence of charge transfer on layer separation. Our study provides experimental and conceptual foundations for generating p-n nanojunctions in 2D materials.Dry-state microsampling techniques are convenient and advantageous for sample collection in resource-limited settings, including healthcare systems designed for the underserved population. In this work, a microsampling platform based on an embossed hydrophobic paper substrate is introduced together with three-dimensional (3D) printed cartridges that offer opportunities for rapid ( less then 30 min) drying of the collected samples while also preserving sample integrity when the embossed paper chip is shipped at room temperature. More importantly, a new pinhole paper spray ionization method was developed that facilitates direct mass spectrometry (MS) analysis of the dried blood samples without prior sample preparation. We compared the direct pinhole paper spray MS method with a liquid chromatographic (LC) MS approach that relied upon electrospray ionization (ESI) after analytes present in the blood sample were extracted through liquid-liquid extraction. Limits of detection as low as 0.12 and 0.49 ng/mL were calculated for cocaine and its metabolite benzoylecgonine, respectively, when using the direct pinhole paper spray MS method. Analytical merits such as precision and accuracy, recovery, carryover effects, and analyte stability were all quantified for this new paper spray method and compared to the traditional LC-ESI-MS. Although LC-ESI-MS was observed to be 10× more sensitive, the linear dynamic range for both methods was determined to be the same, in the range of 1-500 ng/mL for both cocaine and benzoylecgonine analytes. When fully developed, the current microsampling strategy could offer an easy-to-use kit that can enable a more effective MS analysis of 20 μL dried blood samples delivered by mail. Both sensitivity (10×) and sample stability are found to be more superior for blood prepared in the embossed hydrophobic paper compared to samples prepared in the planar hydrophilic paper.The uncontrolled deposition/dissolution process of lithium dendrites during electrochemical cycling in batteries limits the large-scale application of Li metal anodes. Investigating the microstructure of Li dendrites is a focal point. Currently, the only way to protect and observe sensitive Li dendrites is through low-temperature transmission electron microscopy (LT-TEM), whereas room-temperature characterization is still lacking. In this work, the room-temperature microstructure of Li dendrites was obtained by TEM using both vacuum- and inert-gas-transfer methods. Detailed comparison between LT- and room-temperature (RT-)TEM characterizations was provided to show the pros and cons of each method. Especially, RT-TEM shows the advantage of flexible incorporation with multifunctional characterizations, such as 3D tomography. By using RT-TEM, microstructural evolution of Li dendrites during the electrodeposition/dissolution process, including increase of the quantity of inorganic Li2O compounds in the solid electrolyte interphase, lateral growth behavior, and two types of inactive Li, has been revealed, enriching the understanding of the structure-property relationship of Li dendrites.We analyzed first-dose coronavirus disease vaccination coverage among US children 5-11 years of age during November-December 2021. Pediatric vaccination coverage varied widely by jurisdiction, age group, and race/ethnicity, and lagged behind vaccination coverage for adolescents aged 12-15 years during the first 2 months of vaccine rollout.During the 2018 Lassa fever outbreak in Nigeria, samples from patients with suspected Lassa fever but negative Lassa virus PCR results were processed through custom gene expression array cards and metagenomic sequencing. Results demonstrated no single etiology, but bacterial and viral pathogens (including mixed co-infections) were detected.

Enzyme replacement therapy (ERT) with idursulfase is available for patients with mucopolysaccharidosis (MPS) type II, and improvements in certain somatic signs and symptoms have been reported. The aim of the study was to assess the effectiveness of ERT with idursulfase (Elaprase®) on the passive joint range of motion (JROM) in the upper and lower extremities of patients with MPS II.

The study included 16 Polish patients diagnosed with MPS II and followed in our Institute in the years 2009-2016. The study group was divided for groups of neuronopathic (group 1, n=12) and non-neuronopathic (group 2, n=4) patients. A passive JROM was measured with a goniometer by one physiotherapist, while in group 1 it was assessed at baseline and after both short-term (52 weeks) and long-term (mean 230 weeks, range 108-332 weeks) ERT. In group 2, it was assessed at baseline and after short-term ERT (68-85 weeks, no data for long-term ERT).

In group 1, after 52 weeks of ERT, we observed some improvement of passive ROM in wrist flexion (5/12 patients), shoulder abduction and wrist extension (3/12 patients), shoulder flexion, elbow and knee extension (2/12 patients).