The direct, site-selective alkylation of unactivated C(sp3)–H bonds in organic substrates is a long-standing goal in synthetic chemistry. General approaches to the activation of strong C–H bonds ...include radical-mediated processes involving highly reactive intermediates, such as heteroatom-centered radicals. Herein, we describe a catalytic, intermolecular C–H alkylation that circumvents such reactive species via a new elementary step for C–H cleavage involving multisite-proton-coupled electron transfer (multisite-PCET). Mechanistic studies indicate that the reaction is catalyzed by a noncovalent complex formed between an iridium(III) photocatalyst and a monobasic phosphate base. The C–H alkylation proceeds efficiently using diverse hydrocarbons and complex molecules as the limiting reagent and represents a new approach to the catalytic functionalization of unactivated C(sp3)–H bonds.
The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves ...propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.
ABSTRACT We present observational evidence of compressible MHD wave modes propagating from the solar photosphere through to the base of the transition region in a solar magnetic pore. High cadence ...images were obtained simultaneously across four wavelength bands using the Dunn Solar Telescope. Employing Fourier and wavelet techniques, sausage-mode oscillations displaying significant power were detected in both intensity and area fluctuations. The intensity and area fluctuations exhibit a range of periods from 181 to 412 s, with an average period ∼290 s, consistent with the global p-mode spectrum. Intensity and area oscillations present in adjacent bandpasses were found to be out of phase with one another, displaying phase angles of 6 12, 5 82, and 15 97 between the 4170 continuum-G-band, G-band-Na i D1, and Na i D1-Ca ii K heights, respectively, reiterating the presence of upwardly propagating sausage-mode waves. A phase relationship of ∼0° between same-bandpass emission and area perturbations of the pore best categorizes the waves as belonging to the "slow" regime of a dispersion diagram. Theoretical calculations reveal that the waves are surface modes, with initial photospheric energies in excess of 35,000 W m−2. The wave energetics indicate a substantial decrease in energy with atmospheric height, confirming that magnetic pores are able to transport waves that exhibit appreciable energy damping, which may release considerable energy into the local chromospheric plasma.
Purpose
Acute graft versus host disease (aGVHD) is a major cause of non-relapse morbidity and mortality post-allogenic hematopoietic stem cell transplant (HSCT). Using conventional literature search ...and computational approaches, our objective was to identify oral and gut bacterial species associated with aGVHD, potentially affecting drug treatment via lipopolysaccharide (LPS) pathways.
Methods
Medline, PubMed, PubMed Central, and Google Scholar were searched using MeSH terms. The top 100 hits per database were curated, and 25 research articles were selected to examine oral and gut microbiomes associated with health, HSCT, and aGVHD. Literature search validation, aGVHD drug targets, and microbial metabolic pathway identification were completed using BioReader, MACADAM, KEGG, and STRING programs.
Results
Our review determined that (1) oral genera
Rothia
,
Solobacterium
, and
Veillonella
were identified in HSCT patients’ stool and associated with aGVHD; (2) shifts in gut
enterococci
profiles were determined in HSCT-associated aGVHD; (3) gut microbiome dysbiosis prior or during HSCT and lower Shannon diversity index at time of HSCT were also associated with increased risk of aGVHD and transplant related death; and (4) Coriobacteriaceae family was negatively correlated with gut aGVHD, whereas
Eubacterium limosum
was associated with decreased risk of chronic GVHD relapse.
Additionally, we identified molecular pathways related to TLR4/ LPS, including candidate aGVHD drug targets, impacted by oral and gut bacterial taxa.
Conclusion
Reduced microbial diversity reflects higher severity and mortality rate in HSCT patients with aGVHD. Multi-omics approaches to decipher oral and gut microbiome associations will be critical for developing aGVHD preventive therapies.
Abstract Domestic dogs ( Canis familiaris ) housed in kennelling establishments are considered at risk of suffering poor welfare. Previous research supporting this hypothesis has typically used ...cortisol:creatinine ratios (C/Cr) to measure acute and chronic stress in kennelled dogs. However, the value of C/Cr as a welfare indicator has been questioned. This study aimed to test the validity of a range of physiological, physical and behavioural welfare indicators and to establish baseline values reflecting good dog welfare. Measurements were taken from 29 privately-owned dogs (14 males, 15 females), ranging in age and breed, in their own home and in a boarding kennel environment, following a within-subjects, counterbalanced design. Pairwise comparisons revealed that C/Cr and vanillylmandelic acid:creatinine ratios (VMA/Cr) were higher in the kennel than home environment ( P = 0.003; P = 0.01, respectively) and were not associated with differences in movement/exercise between environments. Dogs' surface temperature was lower in kennels ( P = 0.001) and was not associated with ambient temperature. No association with age, or effects of kennel establishment, kennelling experience, sex or source were found. Dogs were generally more active in kennels, but showed considerable individual variability. C/Cr and 5-HIAA:creatinine ratios (5-HIAA/Cr) were negatively correlated with lip licking in kennels. Baseline values for each parameter are presented. The emotional valence of responses was ambiguous and no definitive evidence was found to suggest that dogs were negatively stressed by kennelling. It was concluded that C/Cr and, particularly, VMA/Cr and surface temperature provide robust indicators of psychological arousal in dogs, while spontaneous behaviour might be better used to facilitate interpretation of physiological and physical data on an individual level.
Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to ...radiation dose and specific chemotherapeutic agents.
We conducted an international case–control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls.
Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5–158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m2 of procarbazine with nitrogen mustard or ≥3900 mg/m2 of cyclophosphamide.
Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks.
In May of 2011, NASA selected the
O
rigins,
S
pectral
I
nterpretation,
R
esource
I
dentification, and
S
ecurity–
R
egolith
Ex
plorer (OSIRIS-REx) asteroid sample return mission as the third mission ...in the New Frontiers program. The other two New Frontiers missions are
New Horizons
, which explored Pluto during a flyby in July 2015 and is on its way for a flyby of Kuiper Belt object 2014 MU69 on January 1, 2019, and
Juno
, an orbiting mission that is studying the origin, evolution, and internal structure of Jupiter. The spacecraft departed for near-Earth asteroid (101955) Bennu aboard an United Launch Alliance Atlas V 411 evolved expendable launch vehicle at 7:05 p.m. EDT on September 8, 2016, on a seven-year journey to return samples from Bennu. The spacecraft is on an outbound-cruise trajectory that will result in a rendezvous with Bennu in November 2018. The science instruments on the spacecraft will survey Bennu to measure its physical, geological, and chemical properties, and the team will use these data to select a site on the surface to collect at least 60 g of asteroid regolith. The team will also analyze the remote-sensing data to perform a detailed study of the sample site for context, assess Bennu’s resource potential, refine estimates of its impact probability with Earth, and provide ground-truth data for the extensive astronomical data set collected on this asteroid. The spacecraft will leave Bennu in 2021 and return the sample to the Utah Test and Training Range (UTTR) on September 24, 2023.
Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy ...use.
Nested case–control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records.
The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (Ptrend < 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 95% confidence interval (CI) 2.7–28. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2–0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking).
Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.
In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N=22) viewed ...neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. NeuroImage, 23(2), 483–499, connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6), 502–510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., Iidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. NeuroImage, 29 (3), 721–733 and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors.
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