UV solar irradiance in observations and the NRLSSI and SATIRE-S models

Total solar irradiance and UV spectral solar irradiance have been monitored since 1978 through a succession of space missions. This is accompanied by the development of models aimed at replicating solar irradiance by relating the variability to solar magnetic activity. The NRLSSI and SATIRE-S models provide the most comprehensive reconstructions of total and spectral solar irradiance over the period of satellite observation currently available. There is persistent controversy between the various measurements and models in terms of the wavelength dependence of the variation over the solar cycle, with repercussions on our understanding of the influence of UV solar irradiance variability on the stratosphere. We review the measurement and modelling of UV solar irradiance variability over the period of satellite observation. The SATIRE-S reconstruction is consistent with spectral solar irradiance observations where they are reliable. It is also supported by an independent, empirical reconstruction of UV spectral solar irradiance based on UARS/SUSIM measurements from an earlier study. The weaker solar cycle variability produced by NRLSSI between 300 and 400 nm is not evident in any available record. We show that although the method employed to construct NRLSSI is principally sound, reconstructed solar cycle variability is detrimentally affected by the uncertainty in the SSI observations it draws upon in the derivation. Based on our findings, we recommend, when choosing between the two models, the use of SATIRE-S for climate studies

Nickel-Catalyzed Intramolecular Alkene Difunctionalization by Ball-Milling

A mechanochemical nickel-catalyzed intramolecular difunctionalization reaction of alkene tethered aryl halides with alkyl halides is herein described. This method allows for synthesis of 3,3-disubstituted heterocycles, namely oxindoles, with shorter reaction times than solution-phase counterparts. Additionally, this process is solvent minimized, with DMA used in liquid-assisted grinding (LAG) quantities and circumvents the need for chemical activation of the terminal reductant (manganese) through mechanical grinding. The process can be scaled up to yield over a gram of product and modest enantioinduction is possible by utilizing a chiral PyrOx ligand. (Figure presented.)

FLP-catalyzed transfer hydrogenation of silyl enol ethers

Herein we report the first catalytic transfer hydrogenation of silyl enol ethers. This metal free approach employs tris(pentafluorophenyl)borane and 2,2,6,6‐tetramethylpiperidine (TMP) as a commercially available FLP catalyst system and naturally occurring γ‐terpinene as a dihydrogen surrogate. A variety of silyl enol ethers undergo efficient hydrogenation, with the reduced products isolated in excellent yields (29 examples, 82% average yield)

Bicyclic Boronate β-Lactamase Inhibitors: The Present Hope against Deadly Bacterial Pathogens

The use of β-lactamase inhibitors in combination with β-lactam antibiotics is an emerging area in drug discovery. This strategy allows the restoration of the therapeutic efficacy of these antibiotics in clinical use against multiresistant bacteria. These pathogens are drug resistant because they express β-lactamase enzymes, which prevent the antibiotic therapeutic action by catalyzing the hydrolysis of the β-lactam ring. These enzymes are quite diverse in both their structural architecture and hydrolytic capability, as well as in the mechanism of action. The ever-increasing emergence of pathogens that are capable of coproducing different types of β-lactamases has triggered the search for ultrabroad-spectrum inhibitors capable of deactivating both serine- and metallo-β-lactamases. A recent breakthrough in this long-pursued and unmet need is the discovery of bicyclic boronate inhibitors, specifically taniborbactam, VNRX-7145, and QPX7728, which are currently under clinical development in combination with cefepime, ceftibuten, and QPX2014, respectively. The present article highlights the therapeutic potential of these inhibitors and their spectrum of efficacy is compared with those of other β-lactam/β-lactamase inhibitor combinations recently approved by the food and drug administration. The molecular basis of the ultrabroad-spectrum of activity of boron-based inhibitors is also discussed, on the basis of the available crystal structures and the results of computational studiesinancial support from the Spanish Ministry of Economy and Competiveness (SAF2016-75638-R, PID2019-105512RB-I00), the Xunta de Galicia [ED431B 2018/04 and Centro singular de investigación de Galicia accreditation 2019–2022 (ED431G 2019/03)], and the European Regional Development Fund (ERDF) is gratefully acknowledgedS

Leukocyte function and health status of calves supplemented with vitamins A and E

Forty-four Holstein calves were fed milk replacers with varied concentrations of vitamins A and E from 3 to 45 d of age to determine their effects on concentrations of plasma vitamin A (retinol and retinyl palmitate) and vitamin E (a- tocopherol), lymphocyte and neutrophil functions, and health of calves. Plasma a-tocopherol was unaffected by increased vitamin A supplementation. Fecal scores, and eye and nose membrane responses were improved with increased vitamin A and lower vitamin E concentration, whereas the same treatment tended to reduce neutrophil cytotoxic and bactericidal activity by 6 wk of age. Increased supplemental vitamin E tended to enhance neutrophil functions. However, age appeared to have an effect on response to both vitamins

Frustrated Lewis pair (FLP)-catalyzed hydrogenation of aza-Morita–Baylis–Hillman adducts and sequential organo-FLP catalysis

Herein we report the metal-free diastereoselective frustrated Lewis pair (FLP)-catalyzed hydrogenation of aza-Morita–Baylis–Hillman (aza-MBH) adducts, accessing a diverse range of stereodefined β-amino acid derivatives in excellent isolated yields (28 examples, 89% average yield, up to 90:10 d.r.). Furthermore, sequential organo-FLP catalysis has been developed. An initial organocatalyzed aza-MBH reaction followed by in situ FLP formation and hydrogenation of the electron-deficient α,β-unsaturated carbonyl compounds can be performed in one-pot, using DABCO as the Lewis base in both catalytic steps

Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates

Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

N-Heterocyclic carbene acyl anion organocatalysis by ball-milling

The ability to conduct N‐heterocyclic carbene‐catalysed acyl anion chemistry under ball‐milling conditions is reported for the first time. This process has been exemplified through applications to intermolecular‐benzoin, intramolecular‐benzoin, intermolecular‐Stetter and intramolecular‐Stetter reactions including asymmetric examples and demonstrates that this mode of mechanistically complex organocatalytic reaction can operate under solvent‐minimised conditions

One-pot synthesis of styrene derivatives from allyl silanes via b(c6f5)3-catalyzed isomerization-Hiyama coupling

Herein, we report a one-pot synthesis of styrene derivatives via a novel B(C6F5)3-catalyzed E-selective isomerization of readily accessible allyl silanes and subsequent Hiyama coupling of the versatile alkenyl silane intermediates. This one-pot, two-step approach enables access to a broad range of styrene derivatives, including those containing Lewis basic functional groups, that cannot be accessed via the previously developed B(C6F5)3-catalyzed isomerization of allyl benzenes

Mechanochemical organocatalysis: do high enantioselectivities contradict what we might expect?

Ball mills input energy to samples by pulverising the contents of the jar. Each impact on the sample or wall of the jar results in an instantaneous transmission of energy in the form of a temperature and pressure increase (volume reduction). Conversely, enantioselective organocatalytic reactions proceed through perceived delicate and well-organised transition states. Does there exist a dichotomy in the idea of enantioselective mechanochemical organocatalysis? This Review provides a survey of the literature reporting the combination of organocatalytic reactions with mechanochemical ball milling conditions. Where possible, direct comparisons of stirred in solution, stirred neat and ball milled processes are drawn with a particular focus on control of stereoselectivity