Redox events in which an electron and proton are exchanged in a concerted elementary step are commonly referred to as proton-coupled electron transfers (PCETs). PCETs are known to operate in numerous ...important biological redox processes, as well as recent inorganic technologies for small molecule activation. These studies suggest that PCET catalysis might also function as a general mode of substrate activation in organic synthesis. Over the past three years, our group has worked to advance this hypothesis and to demonstrate the synthetic utility of PCET through the development of novel catalytic radical chemistries. The central aim of these efforts has been to demonstrate the ability of PCET to homolytically activate a wide variety of common organic functional groups that are energetically inaccessible using known molecular H atom transfer catalysts. To do so, we made use of a simple formalism first introduced by Mayer and co-workers that allowed us to predict the thermodynamic capacity of any oxidant/base or reductant/acid pair to formally add or remove H· from a given substrate. With this insight, we were able to rationally select catalyst combinations thermodynamically competent to homolyze the extraordinarily strong E–H σ-bonds found in many common protic functional groups (BDFEs > 100 kcal/mol) or to form unusually weak bonds to hydrogen via the reductive action of common organic π-systems (BDFEs < 35 kcal/mol). These ideas were reduced to practice through the development of new catalyst systems for reductive PCET activations of ketones and oxidative PCET activation of amide N–H bonds to directly furnish reactive ketyl and amidyl radicals, respectively. In both systems, the reaction outcomes were found to be successfully predicted using the effective bond strength formalism, suggesting that these simple thermochemical considerations can provide useful and actionable insights into PCET reaction design. The ability of PCET catalysis to control enantioselectivity in free radical processes has also been established. Specifically, multisite PCET requires the formation of a pre-equilibrium hydrogen bond between the substrate and a proton donor/acceptor prior to charge transfer. We recognized that these H-bond interfaces persist following the PCET event, resulting in the formation of noncovalent complexes of the nascent radical intermediates. When chiral proton donors/acceptors are employed, this association can provide a basis for asymmetric induction in subsequent bond-forming steps. We discuss our efforts to capitalize on this understanding via the development of a catalytic protocol for enantioselective aza-pinacol cyclizations. Lastly, we highlight an alternative PCET mechanism that exploits the ability of redox-active metals to homolytically weaken the bonds in coordinated ligands, enabling nominally strong bonds (BDFEs ∼ 100 kcal) to be abstracted by weak H atom acceptors with concomitant oxidation of the metal center. This “soft homolysis” mechanism enables the generation of metalated intermediates from protic substrates under completely neutral conditions. The first example of this form of catalysis is presented in the context of a catalytic C–N bond forming reaction jointly mediated by bulky titanocene complexes and the stable nitroxyl radical TEMPO.
For numerous taxa, species richness is much higher in tropical than in temperate zone habitats. A major challenge in community ecology and evolutionary biogeography is to reveal the mechanisms ...underlying these differences. For herbivorous insects, one such mechanism leading to an increased number of species in a given locale could be increased ecological specialization, resulting in a greater proportion of insect species occupying narrow niches within a community. We tested this hypothesis by comparing host specialization in larval Lepidoptera (moths and butterflies) at eight different New World forest sites ranging in latitude from 15° S to 55° N. Here we show that larval diets of tropical Lepidoptera are more specialized than those of their temperate forest counterparts: tropical species on average feed on fewer plant species, genera and families than do temperate caterpillars. This result holds true whether calculated per lepidopteran family or for a caterpillar assemblage as a whole. As a result, there is greater turnover in caterpillar species composition (greater β diversity) between tree species in tropical faunas than in temperate faunas. We suggest that greater specialization in tropical faunas is the result of differences in trophic interactions; for example, there are more distinct plant secondary chemical profiles from one tree species to the next in tropical forests than in temperate forests as well as more diverse and chronic pressures from natural enemy communities.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Marine spatial planning (MSP) seeks to reduce conflicts and environmental impacts, and promote sustainable use of marine ecosystems. Existing MSP approaches have successfully determined how to ...achieve target levels of ocean area for particular uses while minimizing costs and impacts, but they do not provide a framework that derives analytical solutions in order to co-ordinate siting of multiple uses while balancing the effects of planning on each sector in the system. We develop such a framework for guiding offshore aquaculture (bivalve, finfish, and kelp farming) development in relation to existing sectors and environmental concerns (wild-capture fisheries, viewshed quality, benthic pollution, and disease spread) in California, USA. We identify > 250,000 MSP solutions that generate significant seafood supply and billions of dollars in revenue with minimal impacts (often < 1%) on existing sectors and the environment. We filter solutions to identify candidate locations for high-value, low-impact aquaculture development. Finally, we confirm the expectation of substantial value of our framework over conventional planning focused on maximizing individual objectives.
Thirty-eight Angus-cross beef cows were used to evaluate differences in DMI, residual feed intake (RFI), and endocrine markers on the basis of cow size and RFI ranking during 2 stages of production. ...Cows housed in individual pens (2.2 × 9.1 m) were fed, over a 70-d feeding period, 30% Bermuda grass hay and 70% ryegrass baleage diet during lactation (LACT) and a 100% ryegrass hay diet during postweaning (NOLACT). Individual daily feed intake, BW, and BCS were recorded, and hip height was used to determine frame score (FS). Feed intake was used to calculate RFI for each cow, and cow was the experimental unit. Blood samples were obtained on d 0 and 70 and were analyzed for glucose, insulin, leptin, triiodothyronine (T3), and thyroxine (T4). Cows were assigned to a light (LIT) or heavy (HEV) BW groups on the basis of mean BW at the beginning of the LACT period. On the basis of RFI values for each feeding period, cows were placed into a negative (NEG; RFI < 0.00) or positive (POS; RFI > 0.00) RFI group and into a low (LOW; ≤0.2 SD mean RFI), medium (MED; within ±0.19 SD), or high (HI; ≥0.2 SD mean RFI) RFI group. During LACT, DMI was 4.8% greater (P = 0.03) and FS was greater (P < 0.01; 6.4 and 5.5 ± 0.16) for the HEV compared with LIT BW cows. No RFI by day interaction or RFI group main effect occurred for endocrine markers during LACT; however, a negative relationship (P = 0.04) existed between BW group and combined T3 data, and a positive relationship (P = 0.04) existed between RFI and combined insulin data. For both LACT and NOLACT, RFI was similar (P > 0.05) among BW groups; however, DMI was 6.5% and 8.9% greater (P < 0.01) for POS compared with NEG RFI in the LACT and NOLACT periods. In LACT, DMI was greater (P < 0.01) for HI and MED RFI compared with LOW RFI, and in NOLACT, DMI was greater (P < 0.01) for the HI compared with MED and LOW RFI cows and MED compared with LOW RFI cows. During NOLACT, DMI was 8.9% greater (P < 0.01) for the HEV (12.4 ± 0.22 kg) compared with LIT (11.3 ± 0.19 kg) BW cows. Change in BCS was greater (P ≤ 0.03) in higher RFI cows in both RFI groups only in the NOLACT period. Differences in T3 and T4 on d 0 and 70 were 25% and 15% greater (P ≤ 0.04) for the LIT BW group compared with the HEV BW group. A negative correlation existed (P ≤ 0.04) between BW group and T3 and T4, as well as leptin and RFI (P = 0.03). Although cow BW was independent of RFI and T3 and T4 levels tended to be greater in lighter BW cows, DMI was consistently greater for cows with heavier BW and higher RFIvalues.
Patients infected with the SARS-CoV-2 virus can present with a wide variety of symptoms including being entirely asymptomatic. Despite having no or minimal symptoms, some patients may have markedly ...reduced pulse oximetry readings. This has been referred to as “silent” or “apathetic” hypoxia (Ottestad et al., 2020 1). We present a case of a 72-year-old male with COVID-19 syndrome who presented to the emergency department with minimal symptoms but low peripheral oxygen saturation readings. The patient deteriorated over the following days and eventually died as a result of overwhelming multi-organ system failure. This case highlights the utility of peripheral oxygen measurements in the evaluation of patients with SARS-CoV-2 infection. Self-monitoring of pulse oximetry by patients discharged from the emergency department is a potential way to identify patients needing to return for further evaluation.
While interest in the synthetic chemistry of radical cations continues to grow, controlling enantioselectivity in the reactions of these intermediates remains a challenge. Based on recent insights ...into the oxidation of tryptophan in enzymatic systems, we report a photocatalytic method for the generation of indole radical cations as hydrogen-bonded adducts with chiral phosphate anions. These noncovalent open-shell complexes can be intercepted by the stable nitroxyl radical TEMPO· to form alkoxyamine-substituted pyrroloindolines with high levels of enantioselectivity. Further elaboration of these optically enriched adducts can be achieved via a catalytic single-electron oxidation/mesolytic cleavage sequence to furnish transient carbocation intermediates that may be intercepted by a wide range of nucleophiles. Taken together, this two-step sequence provides a simple catalytic method to access a wide range of substituted pyrroloindolines in enantioenriched form via a standard experimental protocol from a common synthetic intermediate. The design, development, mechanistic study, and scope of this process are presented, as are applications of this method to the synthesis of several dimeric pyrroloindoline natural products.
Model for End‐stage Liver Disease (MELD)‐based allocation of deceased donor livers allows exceptions for patients whose score may not reflect their true mortality risk. We hypothesized that organ ...procurement organizations (OPOs) may differ in exception practices, use of exceptions may be increasing over time, and exception patients may be advantaged relative to other patients. We analyzed longitudinal MELD score, exception and outcome in 88 981 adult liver candidates as reported to the United Network for Organ Sharing from 2002 to 2010. Proportion of patients receiving an HCC exception was 0–21.4% at the OPO‐level and 11.9–18.8% at the region level; proportion receiving an exception for other conditions was 0.0%–13.1% (OPO‐level) and 3.7–9.5 (region‐level). Hepatocellular carcinoma (HCC) exceptions rose over time (10.5% in 2002 vs. 15.5% in 2008, HR = 1.09 per year, p<0.001) as did other exceptions (7.0% in 2002 vs. 13.5% in 2008, HR = 1.11, p<0.001). In the most recent era of HCC point assignment (since April 2005), both HCC and other exceptions were associated with decreased risk of waitlist mortality compared to nonexception patients with equivalent listing priority (multinomial logistic regression odds ratio OR = 0.47 for HCC, OR = 0.43 for other, p<0.001) and increased odds of transplant (OR = 1.65 for HCC, OR = 1.33 for other, p<0.001). Policy advantages patients with MELD exceptions; differing rates of exceptions by OPO may create, or reflect, geographic inequity.
This analysis of patient outcomes on the deceased donor liver wait list shows that patients with MELD exceptions die at lower rates, and are transplanted at higher rates, than equivalent patients without exceptions. See editorial by Freeman on page 2271.
Severe geographic disparities exist in liver transplantation; for patients with comparable disease severity, 90‐day transplant rates range from 18% to 86% and death rates range from 14% to 82% across ...donation service areas (DSAs). Broader sharing has been proposed to resolve geographic inequity; however, we hypothesized that the efficacy of broader sharing depends on the geographic partitions used. To determine the potential impact of redistricting on geographic disparity in disease severity at transplantation, we combined existing DSAs into novel regions using mathematical redistricting optimization. Optimized maps and current maps were evaluated using the Liver Simulated Allocation Model. Primary analysis was based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 Model of End‐Stage Liver Disease (MELD) changes in 2010. Fully regional sharing within the current regional map would paradoxically worsen geographic disparity (variance in MELD at transplantation increases from 11.2 to 13.5, p = 0.021), although it would decrease waitlist deaths (from 1368 to 1329, p = 0.002). In contrast, regional sharing within an optimized map would significantly reduce geographic disparity (to 7.0, p = 0.002) while achieving a larger decrease in waitlist deaths (to 1307, p = 0.002). Redistricting optimization, but not broader sharing alone, would reduce geographic disparity in allocation of livers for transplant across the United States.
Full regional sharing of liver offers within the existing regions would paradoxically increase geographic inequity, but using optimal redistricting to design novel regions would make liver allocation more geographically equitable. See editorial by Yeh and Hunsicker on page 1949.
Insect outbreaks are expected to increase in frequency and intensity with projected changes in global climate through direct effects of climate change on insect populations and through disruption of ...community interactions. Although there is much concern about mean changes in global climate, the impact of climatic variability itself on species interactions has been little explored. Here, we compare caterpillar-parasitoid interactions across a broad gradient of climatic variability and find that the combined data in 15 geographically dispersed databases show a decrease in levels of parasitism as climatic variability increases. The dominant contribution to this pattern by relatively specialized parasitoid wasps suggests that climatic variability impairs the ability of parasitoids to track host populations. Given the important role of parasitoids in regulating insect herbivore populations in natural and managed systems, we predict an increase in the frequency and intensity of herbivore outbreaks through a disruption of enemy-herbivore dynamics as climates become more variable.
Young stars typically form in star clusters, so the supernovae (SNe) they produce are clustered in space and time. This clustering of SNe may alter the momentum per SN deposited in the interstellar ...medium (ISM) by affecting the local ISM density, which in turn affects the cooling rate. We study the effect of multiple SNe using idealized 1D hydrodynamic simulations which explore a large parameter space of the number of SNe, and the background gas density and metallicity. The results are provided as a table and an analytic fitting formula. We find that for clusters with up to ~100 SNe, the asymptotic momentum scales superlinearly with the number of SNe, resulting in a momentum per SN which can be an order of magnitude larger than for a single SN, with a maximum efficiency for clusters with 10-100 SNe. We argue that additional physical processes not included in our simulations -- self-gravity, breakout from a galactic disc, and galactic shear -- can slightly reduce the momentum enhancement from clustering, but the average momentum per SN still remains a factor of 4 larger than the isolated SN value when averaged over a realistic cluster mass function for a star-forming galaxy. We conclude with a discussion of the possible role of mixing between hot and cold gas, induced by multidimensional instabilities or pre-existing density variations, as a limiting factor in the build-up of momentum by clustered SNe, and suggest future numerical experiments to explore these effects.
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