Dipicolinate vanadium(V) complexes oxidize lignin model complexes pinacol monomethyl ether (A), 2-phenoxyethanol (B), 1-phenyl-2-phenoxyethanol (C), and 1,2-diphenyl-2-methoxyethanol (D). With ...substrates having C−H bonds adjacent to the alcohol moiety (B−D), the C−H bond is broken in pyridine-d 5 solvent, yielding 2-phenoxyacetaldehyde from B, 2-phenoxyacetophenone from C, and benzoin methyl ether from D. In DMSO-d 6 solvent the reaction is slower, and both C−H and C−C bond cleavage products are observed for D. The vanadium(IV) products of these reactions have been identified and characterized. Catalytic oxidation of C and D has been demonstrated using air and (dipic)V(O)OiPr. For both substrates, the C−C bond between the alcohol and ether groups is broken in the catalytic oxidation. 1-Phenyl-2-phenoxyethanol is oxidized to a mixture of phenol, formic acid, benzoic acid, and 2-methoxyacetophenone. The products of oxidation of 1,2-diphenyl-2-methoxyethanol depend on the solvent; in DMSO benzaldehyde and methanol are the major products, while benzoic acid and methyl benzoate are the major products obtained in pyridine solvent. Phenyl substituents on the model complex facilitate the oxidation, with relative rates of oxidation D > C > B.
Prior studies demonstrated that deletion of the protein phosphatase Phlpp1 in Ctsk-Cre expressing cells enhances bone mass, characterized by diminished osteoclast activity and increased coupling to ...bone formation. Due to non-specific expression of Ctsk-Cre, the definitive mechanism for this observation was unclear. To further define the role of bone resorbing osteoclasts, we performed ovariectomy (Ovx) and Sham surgeries on Phlpp1 cKO.sub.Ctsk and WT mice. Micro-CT analyses confirmed enhanced bone mass of Phlpp1 cKO.sub.Ctsk Sham females. In contrast, Ovx induced bone loss in both groups, with no difference between Phlpp1 cKO.sub.Ctsk and WT mice. Histomorphometry demonstrated that Ovx mice lacked differences in osteoclasts per bone surface, suggesting that estradiol (E2) is required for Phlpp1 deficiency to have an effect. We performed high throughput unbiased transcriptional profiling of Phlpp1 cKO.sub.Ctsk osteoclasts and identified 290 differentially expressed genes. By cross-referencing these differentially expressed genes with all estrogen response element (ERE) containing genes, we identified IGFBP4 as potential estrogen-dependent target of Phlpp1. E2 induced PHLPP1 expression, but reduced IGFBP4 levels. Moreover, genetic deletion or chemical inhibition of Phlpp1 was correlated with IGFBP4 levels. We then assessed IGFBP4 expression by osteoclasts in vivo within intact 12-week-old females. Modest IGFBP4 immunohistochemical staining of TRAP.sup.+ osteoclasts within WT females was observed. In contrast, TRAP.sup.+ bone lining cells within intact Phlpp1 cKO.sub.Ctsk females robustly expressed IGFBP4, but levels were diminished within TRAP.sup.+ bone lining cells following Ovx. These results demonstrate that effects of Phlpp1 conditional deficiency are lost following Ovx, potentially due to estrogen-dependent regulation of IGFBP4.
While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) ...among fully vaccinated persons by rurality.
We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period.
Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio aHR 1.53, 95% confidence interval CI 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures.
Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.
Vanadium(V) complexes of the tridentate bis(phenolate)pyridine ligand H 2 BPP (H 2 BPP = 2,6-(HOC6H2-2,4-tBu2)2NC5H3) and the bis(phenolate)amine ligand H 2 BPA (H 2 BPA = ...N,N-bis(2-hydroxy-4,5-dimethylbenzyl)propylamine) have been synthesized and characterized. The ability of the complexes to mediate the oxidative C–C bond cleavage of pinacol was tested. Reaction of the complex (BPP)VV(O)(OiPr) (4) with pinacol afforded the monomeric vanadium(IV) product (BPP)VIV(O)(HOiPr) (6) and acetone. Vanadium(IV) complex 6 was oxidized rapidly by air at room temperature in the presence of NEt3, yielding the vanadium(V) cis-dioxo complex (BPP)VV(O)2HNEt3. Complex (BPA)VV(O)(OiPr) (5) reacted with pinacol at room temperature, to afford acetone and the vanadium(IV) dimer (BPA)VIV(O)(HOiPr)2. Complexes 4 and 5 were evaluated as catalysts for the aerobic oxidation of 4-methoxybenzyl alcohol and arylglycerol β-aryl ether lignin model compounds. Although both 4 and 5 catalyzed the aerobic oxidation of 4-methoxybenzyl alcohol, complex 4 was found to be a more active and robust catalyst for oxidation of the lignin model compounds. The catalytic activities and selectivities of the bis(phenolate) complexes are compared to previously reported catalysts.
We report 90% yield of electron transfer (ET) from the singlet excited state P* of the primary electron-donor P (a bacteriochlorophyll dimer) to the B-side bacteriopheophytin (HB) in the bacterial ...photosynthetic reaction center (RC). Starting from a platform Rhodobacter sphaeroides RC bearing several amino acid changes, an Arg in place of the native Leu at L185—positioned over one face of HB and only ∼4 Å from the 4 central nitrogens of the HB macrocycle—is the key additional mutation providing 90% yield of P⁺HB⁻. This all but matches the near-unity yield of A-side P⁺HA⁻ charge separation in the native RC. The 90% yield of ET to HB derives from (minimally) 3 P* populations with distinct means of P* decay. In an ∼40% population, P* decays in ∼4 ps via a 2-step process involving a short-lived P⁺BB⁻ intermediate, analogous to initial charge separation on the A side of wild-type RCs. In an ∼50% population, P* → P⁺HB⁻ conversion takes place in ∼20 ps by a superexchange mechanism mediated by BB. An ∼10% population of P* decays in ∼150 ps largely by internal conversion. These results address the long-standing dichotomy of Aversus B-side initial charge separation in native RCs and have implications for the mechanism(s) and timescale of initial ET that are required to achieve a near-quantitative yield of unidirectional charge separation.
The reactivity of copper and vanadium catalysts toward the aerobic oxidation of lignin models has been explored. Both (dipic)VV(O)(OiPr) (3) (dipic = dipicolinate) and CuCl/TEMPO (TEMPO = ...tetramethylpiperidine N-oxide) catalyzed the aerobic oxidation of the lignin model compound 1,2-diphenyl-2-methoxyethanol (2). The vanadium catalyst 3 produced benzoic acid (85%) and methyl benzoate (84%) as the major products via the intermediate ketone benzoin methyl ether (4). The copper catalyzed reaction afforded benzaldehyde (84%) and methylbenzoate (88%) directly, with no intermediate formation of 4. The more complex lignin model system 1-(3,5-dimethoxyphenyl)-2-(2-methoxyphenoxy)propane-1,3-diol-2,3-13C2 (5-13C2) was oxidized under air by vanadium catalyst 3, affording ketone 7-13C2 (65%), dehydrated ketone 8-13C2 (5%), alkene product 9-13C2 (14%), 3,5-dimethoxybenzoic acid (11%), 3,5-dimethoxybenzaldehyde (2%), 2-methoxyphenol, and formic acid-13C1 (4%). Aerobic oxidation of ketone 7-13C2 using catalyst 3 produced dehydrated ketone 8-13C2, 3,5-dimethoxybenzoic acid, and formic acid-13C1, suggesting that 7 is further oxidized under the catalytic conditions. In contrast, oxidation of β-O-4 model 5-13C2 using CuCl/TEMPO affords 3,5-dimethoxybenzaldehyde (43%), 3,5-dimethoxybenzoic acid (13%), 2-methoxyphenol (7%), formic acid-13C1 (7%), ketone-7 13C2 (1%), dehydrated ketone 8-13C2 (2%), and a number of higher molecular weight products, as determined by 1H and 13C NMR, GC-MS, and LC-MS. Attempted oxidation of ketone 7 using CuCl/TEMPO yielded primarily dehydrated ketone 8, indicating that the ketone is not an intermediate in the formation of the aldehyde product. The reactivities of the copper and vanadium catalysts in the oxidation of lignin model compounds 2 and 5 are discussed. Remarkably different selectivities were observed for the vanadium and copper catalyzed reactions, suggesting the potential of homogeneous catalysts for controlling selectivity in the aerobic oxidation of lignin.
We report on studies of the viability and sensitivity of the Askaryan Radio Array (ARA), a new initiative to develop a Teraton-scale ultra-high energy neutrino detector in deep, radio-transparent ice ...near Amundsen-Scott station at the South Pole. An initial prototype ARA detector system was installed in January 2011, and has been operating continuously since then. We describe measurements of the background radio noise levels, the radio clarity of the ice, and the estimated sensitivity of the planned ARA array given these results, based on the first five months of operation. Anthropogenic radio interference in the vicinity of the South Pole currently leads to a few-percent loss of data, but no overall effect on the background noise levels, which are dominated by the thermal noise floor of the cold polar ice, and galactic noise at lower frequencies. We have also successfully detected signals originating from a 2.5km deep impulse generator at a distance of over 3 km from our prototype detector, confirming prior estimates of kilometer-scale attenuation lengths for cold polar ice. These are also the first such measurements for propagation over such large slant distances in ice. Based on these data, ARA-37, the ∼200km2 array now in its initial construction phase, will achieve the highest sensitivity of any planned or existing neutrino detector in the 1016–1019eV energy range.
The 12 best NIR water transition line pairs for temperature measurements with a single DFB laser in flames are determined by systematic analysis of the HITRAN simulation of the water spectra in the ...1--2 *mm spectral region. A specific line pair near 1.4 *mm was targeted for non-intrusive measurements of gas temperature in combustion systems using a scanned-wavelength technique with wavelength modulation and 2f detection. This sensor uses a single diode laser (distributed-feedback), operating near 1.4 *mm and is wavelength scanned over a pair of H2O absorption transitions (7154.354 cm & 7153.748 cm) at a 2 kHz repetition rate. The wavelength is modulated (f=500 kHz) with modulation amplitude a=0.056 cm. Gas temperature is inferred from the ratio of the second harmonic signals of the two selected H2O transitions. The fiber-coupled-single-laser design makes the system compact, rugged, low cost and simple to assemble. As part of the sensor development effort, design rules were applied to optimize the line selection, and fundamental spectroscopic parameters of the selected transitions were determined via laboratory measurements including the temperature-dependent line strength, self-broadening coefficients, and air-broadening coefficients. The new sensor design includes considerations of hardware and software to enable fast data acquisition and analysis; a temperature readout rate of 2 kHz was demonstrated for measurements in a laboratory flame at atmospheric pressure. The combination of scanned-wavelength and wavelength-modulation minimizes interference from emission and beam steering, resulting in a robust temperature sensor that is promising for combustion control applications.
Autoignition characteristics of
n-heptane/air, gasoline/air, and ternary surrogate/air mixtures were studied behind reflected shock waves in a high-pressure, low-temperature regime similar to that ...found in homogeneous charge compression ignition (HCCI) engine cycles. The range of experiments covered combustion of fuel in air for lean, stoichiometric, and rich mixtures (
Φ
=
0.5
, 1.0, 2.0), two pressure ranges (15–25 and 45–60 atm), temperatures from 850 to 1280 K, and exhaust gas recirculation (EGR) loadings of (0, 20, and 30%). The ignition delay time measurements in
n-heptane are in good agreement with the shock tube study of Fieweger et al. (Proc. Combust. Inst. 25 (1994) 1579–1585) and support the observation of a pronounced, low-temperature, NTC region. Strong agreement was seen between ignition delay time measurements for RD387 gasoline and surrogate (63% iso-octane/20% toluene/17%
n-heptane by liquid volume) over the full range of experimental conditions studied. Ignition delay time measurements under fuel-lean
(
Φ
=
0.5
)
mixture conditions were longer than with
Φ
=
1.0
mixtures at both the low- (15–25 atm) and high- (45–60 atm) pressure conditions. Ignition delay times in fuel-rich
(
Φ
=
2.0
)
mixtures for both gasoline and surrogate were indistinguishable in the low-pressure (15–25 atm) range, but were clearly shorter at high-pressures (45–60 atm). EGR loading affected the ignition delay times similarly for both gasoline and surrogate, with clear trends indicating an increase in ignition delay time with increased EGR loading. This data set should provide benchmark targets for detailed mechanism validation and refinement under HCCI conditions.
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